WO2025085835A1

WO2025085835A1 - Manifold systems and devices for applying pulsatile intravascular lithotripsy and methods for same

Info

Publication number: WO2025085835A1
Application number: PCT/US2024/052097
Authority: WO
Inventors: Robert Chisena; Gregory Fisher
Original assignee: Amplitude Vascular Systems Inc
Current assignee: Amplitude Vascular Systems Inc
Priority date: 2023-10-20
Filing date: 2024-10-18
Publication date: 2025-04-24
Anticipated expiration: 2026-04-20

Abstract

Disclosed herein are systems, devices and methods for treating diseased vessels by using pulsatile intravascular lithotripsy. In particular, amplifier assemblies are provided; handle assemblies for controllably transmitting potential energy are also provided; systems for imparting pulsatile energy are provided, where such systems include an amplifier assembly and a handle assembly; and methods for imparting pulsatile energy to tissue are provided.

Description

MANIFOLD SYSTEMS AND DEVICES FOR APPLYING PULSATILE INTRAVASCULAR LITHOTRIPSY AND METHODS FOR SAME

CROSS-REFERENCE TO RELATED APPLICATION

[0001] Pursuant to 35 U.S.C. § 1 19(e), this application claims priority to the filing date of United States provisional patent application serial no. 63,545,060 filed October 20, 2023, the disclosure of which application is incorporated herein by reference in its entirety.

INTRODUCTION

[0002] Ischemic heart disease, the number one cause of death in the world, is caused by atherosclerotic plaque build-up within human vasculature. Worldwide, these diseases represent 84.5% of cardiovascular deaths and 28.2% of overall mortality. Ischemic heart disease is developed through a mechanism called atherosclerosis, which is the accumulation of fatty and calcified materials that cause stenosis, the narrowing of the arterial lumen. Both the coronary and peripheral arteries may suffer from atherosclerotic plaque accumulation. The plaque buildup from atherosclerosis limits blood flow through these arteries and can lead to major adverse cardiovascular events such as myocardial infarction, limb amputation, and mortality. In the early stages of atherosclerosis, plaques are soft and fatty, but as time and the disease progress, these plaques physically harden, or calcify. Calcified plaque (CP) or lesions that develops in the innermost layer of the artery wall occurs most frequently. These CPs result from the deposition and remodeling of calcium hydroxyapatite, a process that mimics bone formation. CP-burdened vessels have reduced vascular elasticity and impaired vessel perfusion. Because of this reduced compliance and perfusion, CPs are associated with an increased risk of mortality and other adverse events.

[0003] While many patients with CP are asymptomatic, a substantial number of patients develop symptoms and signs related to ischemia and undergo endovascular or surgical repair. Given its lower morbidity, endovascular approaches are generally favored. However, CP-burdened vessels pose special challenges for effective intravascular treatments. To treat CP-burdened vessels, a series of devices are often used. The CP- lesion is first pre-dilated using balloon angioplasty (BA). During BA, a balloon is advanced to the affected artery and is expanded to dilate a plaque-burdened vessel to restore normal blood flow. This pre-dilation step must be successful before secondary therapies such as drug-coated balloons or stents can be successfully used. For successful predilation, BA must mechanically fracture the CP to ensure the long-term opening, or patency, of the vessel and to re-establish the elasticity of the surrounding healthy vessel. Often, high-pressure, non-compliant balloons are used to achieve success. However, because of the strength of CP, full balloon expansion is often restricted, and the CP remains unfractured. Without sufficient balloon expansion and CP fracture, the vessel remains with a residual stenosis limiting downstream blood flow indicating a poor outcome, a high risk of immediate or long-term failure, and the need for additional procedures. To ensure patency of diseased vessels, the high rupture strength of the CP must be overcome.

[0004] During standard BA, a pressurized catheter balloon is used to fracture atherosclerotic plaques and expand them into artery walls to re-establish normal blood flow in stenosed arteries. Typically, the balloon is pressurized via a manually actuated screw-driven syringe, which converts rotations of a physician-facing handle into a displacement of the syringe piston. The handle of the syringe is rotated by a clinician until the pressure within the system reaches a desired pressure, or the physician senses fracture of the calcified plaque. During treatment, the physician can sense if the calcified plaque has fractured in two ways: (1 ) from the outline of the balloon under fluoroscopy, a medical imaging technique commonly used in cardiovascular procedures, and (2) from a reduction in pressure within the hydraulic system as indicated by a pressure gauge. During angioplasty procedures, a radiopaque dye (i.e., contrast agent) is introduced into the balloon, which under fluoroscopy, illuminates the outline of the balloon and arterial walls. When the plaque is intact and the balloon is pressurized, the balloon assumes a characteristic dog-bone shape in which the proximal and distal edges are unrestricted to expand but the middle is obstructed by the plaque. The shape of the dog-bone informs the clinician of the severity and distribution of the plaque. A more uniformly expanded balloon indicates to the physician that the plaque has been treated. The second method used to sense plaque fracture is indicated by the pressure gauge attached to the balloon. When treating severe and/or circumferentially distributed plaque, pressure is increased in the balloon until the plaque fractures. Prior to fracture of the plaque, the balloon maintains the previously described dog-bone shape. Upon fracture, the plaque no longer restricts the balloon expansion, and the balloon expands the plaque into the elastic artery. With this balloon expansion, the volume of the balloon increases, transforming it from a dog-bone shape into a fully expanded cylindrical shape. This volume increase causes the pressure in the balloon to drop, a change that may be visualized or sensed from the connected pressure gauge.

[0005] To overcome the rupture strength of CP, angioplasty balloons are often used to aggressively expand CP-burdened vessels. In these cases, balloons are pressurized past their rated burst pressures (i.e., >20-40 ATM of pressure) to achieve sufficient balloon expansion that dilates the artery. These aggressive procedures subject patients to increased risks such as balloon rupture in 21 % of cases, vessel dissection in 76% of cases and restenosis (i.e., post-procedure vessel re-narrowing) in 20-30% of cases. Other treatment strategies that attempt to fracture CP include cutting and scoring BA and lithotripsy BA. Cutting balloons, which are balloons surrounded by sharp-tipped metallic blades, and scoring balloons, which are balloons constrained in a metallic cage, aim to generate stress concentrations for CP fracture. Intravascular lithotripsy employs low- pressure balloons with embedded shockwave-generating lithotripters. Another commonly employed treatment for CP is atherectomy, a technique that uses grinding to debulk CP. Risks from these treatments may include vessel dissection and perforations, injury to healthy tissue surrounding the lesion, and increased risk of restenosis.

[0006] There continues to be a need for improved techniques for balloon angioplasty devices and methods of use, such as devices and systems for intravascular lithotripsy and methods of use.

SUMMARY

[0007] Disclosed herein are systems, devices and methods for treating diseased vessels by using pulsatile intravascular lithotripsy. In particular, amplifier assemblies are provided; handle assemblies for controllably transmitting energy are provided; systems for imparting pulsatile energy are provided, where such systems include an amplifier assembly and a handle assembly; and methods for imparting pulsatile energy to tissue using assemblies and systems of the present invention are also provided.

[0008] Aspects of amplifier assemblies include: a proximal nose, comprising a distal face; a distal waveguide, comprising a proximal face; and a diaphragm sealed between the proximal nose and the distal waveguide separating a proximal chamber from a distal chamber. In some cases, the diaphragm is compressed between the proximal nose and the distal waveguide thereby sealing the proximal chamber from the distal chamber. In embodiments, the diaphragm is configured to translate between the distal face of the proximal nose and proximal face of the distal waveguide. In embodiments, the diaphragm is configured to translate between the distal face of the proximal nose and proximal face of the distal waveguide without producing strain on the diaphragm.

[0009] Aspects of handle assemblies for controllably transmitting energy include: a coupler assembly operably connected to an energy source; a manifold, operably connected to the energy source through the coupler assembly and configured to controllably transmit energy to a distal interface; and the distal interface, operably connected to an output of the manifold and configured to transmit energy received from the manifold.

[0010] Systems for imparting pulsatile energy include: an amplifier assembly and a handle assembly, in each case according to the present invention.

[0011] Methods for imparting pulsatile energy to tissue utilize the assemblies and/or systems disclosed herein.

[0012] In addition, kits comprising components of the amplifier assemblies, handle assemblies and/or systems described herein are provided.

[0013] The assemblies, systems, methods and kits find use in a variety of different applications, including balloon angioplasty applications. BRIEF DESCRIPTION OF THE FIGURES

[0014] The invention may be best understood from the following detailed description when read in conjunction with the accompanying drawings. Included in the drawings are the following figures:

[0015] FIG. 1 A depicts a system according to an embodiment of the invention with an amplifier assembly connected to a handle assembly, in each case according to an embodiment of the invention; FIG. 1 B depicts an isometric view of an amplifier assembly according to an embodiment of the invention; FIG. 10 depicts a view of an amplifier assembly and a handle assembly, in each case according to an embodiment of the invention.

[0016] FIGS. 2A-2B depict amplifier assemblies according to embodiments of the invention. FIG. 2A depicts an internal view of an amplifier assembly according to an embodiment of the invention. FIG. 2B depicts an embodiment of an amplifier assembly in which a clip is employed to securely hold a diaphragm in a sealed position.

[0017] FIGS. 3A-3B depict schematics of a proximal nose of an amplifier assembly according to an embodiment of the invention.

[0018] FIGS. 4A-4B depict schematics of a distal waveguide of an amplifier assembly according to an embodiment of the invention.

[0019] FIGS. 5A-5C depict schematics of a diaphragm of an amplifier assembly according to an embodiment of the invention.

[0020] FIGS. 6A-6C depict schematics of a housing of an amplifier assembly according to an embodiment of the invention.

[0021] FIGS. 7A-7B show exemplary steps for assembling embodiments of amplifier assemblies.

[0022] FIGS. 8A-8F depict different views of aspects of a handle assembly according to an embodiment of the invention.

[0023] FIGS. 9A-9F depict different views of aspects of a handle assembly according to an embodiment of the invention.

[0024] FIGS. 10A-10B present overviews of embodiments of controlling software functionality for systems according to an embodiment of the present invention; FIG. 10C presents an example graphical user interface for controlling and receiving information about a system according to an embodiment of the invention.

[0025] FIG. 1 1 depicts aspects of a system according to an embodiment of the present invention.

[0026] FIG. 12 presents a system for imparting pulsatile energy in accordance with an embodiment of the invention.

[0027] FIG. 13 depicts a proximal nose according to an embodiment of the present invention.

[0028] FIG. 14 depicts a distal waveguide according to an embodiment of the present invention.

[0029] FIGS. 15A-15B depict a diaphragm according to an embodiment of the present invention.

[0030] FIG. 16 depicts a proximal nose according to an embodiment of the present invention.

[0031] FIGS. 17A-17D depict an amplifier assembly according to an embodiment of the present invention.

[0032] In the figures, elements having the same or similar reference numerals have the same or similar features, unless explicitly stated otherwise.

DETAILED DESCRIPTION

[0033] A system for imparting pulsatile energy in accordance with an embodiment of the invention is depicted in FIG. 1A. System 102 includes console 103, CO2 tank 104, amplifier assembly 100, handle assembly 101 , catheter assembly 105 and distal balloon 107. Amplifier assembly 100 and handle assembly 101 are depicted as being operably connected in FIG. 1A; however, amplifier assembly 100 and handle assembly 101 are configured to be disengaged from each other. For example, in certain cases, the handle assembly 101 is reusable, whereas the amplifier assembly 100 is disposable, such that the handle assembly 101 and the amplifier assembly 100 can be disengaged in order to operably connect the handle assembly 101 to another amplifier assembly.

[0034] FIG. 1 A shows system 102 in use. Amplifier assembly 100 is operably connected to catheter assembly 105 at a relatively distal side of amplifier assembly 100. Catheter assembly 105 comprises a tissue-engaging element in a relatively distal region of catheter assembly 105. Tissue-engaging element of catheter assembly 105 comprises distal balloon 107, i.e., a balloon configured to receive pressure pulses displaced from amplifier assembly 100.

[0035] Handle assembly 101 is operably connected to console 103 at a relatively proximal side of handle assembly 101. Console 103 receives energy in the form of pressurized CO2 from CO2 tank 104 and transmits such energy to handle assembly 101 . For ease of use, console 103 is mounted on IV pole 106.

[0036] As described herein, handle assembly 101 of system 102 is configured to receive energy derived from a pressure source, i.e., CO2 tank 104 and console 103, and transmit such energy to amplifier 100. Amplifier assembly 100 of system 102 is configured to convert energy received from handle 101 and ultimately derived from a pressure source, i.e., CO2 tank 104 and console 103, to energy transmitted to catheter assembly 105 and, ultimately, tissue-engaging element, such as distal balloon 107 thereof, to repeatedly pressurize and inflate such balloon 107. Such repeated pressurization and inflation of the distal balloon 107 enables the safe, controlled, fatigue fracture of CP-lesions.

[0037] Amplifier assemblies are provided. Referring to FIG. 2A, aspects of amplifier assemblies include: a proximal nose 210, comprising a distal face 21 1 ; a distal waveguide 260, comprising a proximal face 261 ; and a diaphragm 270 sealed between the proximal nose 210 and the distal waveguide 260 separating a proximal chamber from a distal chamber. In embodiments, the diaphragm 270 is configured to translate between the distal face 211 of the proximal nose 210 and proximal face 261 of the distal waveguide 260 without producing strain on the diaphragm 270.

[0038] Handle assemblies for controllably transmitting energy are also provided. As best shown in FIGS. 8A-8F and FIGS. 9A-9C, aspects of handle assemblies include: a coupler assembly 850 operably connected to an energy source; a manifold 830, operably connected to the energy source through the coupler assembly 850 and configured to controllably transmit energy to a distal interface 810; and the distal interface 810, operably connected to an output of the manifold 830 and configured to transmit energy received from the manifold 830. As described herein, handle assembly 800 operably connects with amplifier assembly 200 through distal interface 810, such as a connection between bore 820 and high-pressure connector 223 shown in FIG. 2A.

[0039] Also provided are systems for imparting pulsatile energy where such systems include: an amplifier assembly and a handle assembly, in each case according to the present invention. Also provided are methods for imparting pulsatile energy to tissue. In addition, kits comprising components of the amplifier assemblies, handle assemblies and/or systems described herein are provided. The assemblies, systems and kits find use in a variety of different applications, including balloon angioplasty applications.

[0040] Systems, assemblies and devices of the present invention, which together or individually provide unibody manifold systems of embodiments of the invention, may be configured to provide, or be operably connected to, one or more tissue-engaging elements, such as a distal end balloon 107 or heart-tissue-conforming element, that imparts pulsatile energy to internal tissue (e.g., luminal vascular tissue, such as an arterial inner wall location) in contact therewith. The energy transmitted from amplifier assembly 200 to balloon 107 is in the form of increasing and decreasing pressure applied at a desired frequency and/or displacement, duty cycle, and amplitude to the internal tissue in contact therewith. As used herein, the frequency is the number of full pressure pulse cycles (peak-to-peak) per unit time; the displacement is the total cyclic change in volume and/or diameter of the balloon, the duty cycle is the percentage of time allocated to the high-pressure segment of a single pressure cycle; and the amplitude is the difference between the maximum and minimum pressure. As the energy imparted by the balloon to the internal tissue is pulsatile, it changes (e.g., increases and decreases) at a defined or determined frequency and duty cycle. During balloon angioplasty (BA) treatment, blood flow distal to the distal end balloon may be occluded, which may limit treatment time. To achieve a successful treatment within this time, the pulsatile frequency and amplitude must impart sufficient energy to the tissue to treat it. While the frequency of pulsatile energy imparted by the balloon to tissue associated therewith may vary, in some instances the frequency is high frequency, ranging in some instances from 0 to 100 Hz, such as 0 to 25 Hz. Similarly, the duty cycle of pulsatile energy imparted by the balloon to tissue may vary ranging in some instances from 10% to 100%, such as 60% to 80%. Change in volume or balloon diameter is dependent on patient anatomy and/or specific balloon size used in surgery. Amplitude of pulsatile energy imparted by the balloon to tissue may vary ranging in some instances from an internal balloon pressure from 0 to 100 ATM, such as 0 to 30 ATM during a given procedure, the frequency may vary over the course of the procedure, i.e., not remain constant, as desired.

[0041] Pulsatile energy, when exposed to diseased luminal vascular tissue, is effective in treating diseased tissue, such as calcified plaque (CP) tissue, while reducing and/or eliminating undesirable effects on surrounding healthy tissue. Important characteristics of pulsatile energy for achieving successful treatments may include the frequency and amplitude of the delivered pulsatile energy. In embodiments, such pulsatile energy can enable the safe, controlled, fatigue fracture of CP-lesions. Fatigue fracture is the process of cyclically loading a structure below the pressure that yields instantaneous shattering and/or crack propagation through the CP-lesions. Whereas conventional treatments apply dangerous high-pressure bursts to the vessel that may create dissections and perforations in surrounding healthy tissue, pulsatile angioplasty employs lower pressure high-frequency oscillations in a balloon to initiate low-pressure fatigue fracture of CP- lesions.

[0042] Generating pulsatile intravascular lithotripsy energy in a catheterization lab or clinic requires a system of connecting, monitoring and maintaining various pressures with minimal to no leakage of fluid and/or gas. Further, the system, and assemblies thereof, must be efficaciously manufacturable. Even further, the system must be capable, reliable, and operationally functional for the end users.

[0043] Before the present invention is described in greater detail, it is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

[0044] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

[0045] Certain ranges are presented herein with numerical values being preceded by the term "about." The term "about" is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.

[0046] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described.

[0047] All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.

[0048] It is noted that, as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. [0049] As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible.

[0050] While the apparatus and method has or will be described for the sake of grammatical fluidity with functional explanations, it is to be expressly understood that the claims, unless expressly formulated under 35 U.S.C. §1 12, are not to be construed as necessarily limited in any way by the construction of "means" or "steps" limitations, but are to be accorded the full scope of the meaning and equivalents of the definition provided by the claims under the judicial doctrine of equivalents, and in the case where the claims are expressly formulated under 35 U.S.C. §1 12 are to be accorded full statutory equivalents under 35 U.S.C. §1 12.

[0051] In further describing various aspects of the invention, amplifier assemblies and components thereof are described first in greater detail. Following this, handle assemblies and components thereof are described. Following this, systems for imparting pulsatile energy comprising an amplifier assembly and a handle assembly are described. Following this a review of methods of using the amplifier assemblies, handle assemblies and systems as well as kits for practicing the subject methods are described.

AMPLIFIER ASSEMBLIES

[0052] Aspects of amplifier assemblies include: a proximal nose, comprising a distal face, a distal waveguide, comprising a proximal face and a diaphragm sealed between the proximal nose and the distal waveguide separating a proximal chamber from a distal chamber. In some cases, the diaphragm is compressed between the proximal nose and the distal waveguide thereby sealing a proximal chamber from a distal chamber. In embodiments, the diaphragm is configured to translate between the distal face of the proximal nose and proximal face of the distal waveguide. In certain embodiments, the diaphragm is configured to translate between the distal face of the proximal nose and proximal face of the distal waveguide without producing strain on the diaphragm.

[0053] To illustrate, in embodiments, the amplifier assembly may be configured to operably connect a tissue-engaging element such as a distal balloon or heart-tissue- conforming element (i.e., operably connected to a catheter connected to the distal waveguide of an amplifier assembly) to an energy source, such as a pressure source (i.e., operably connected to a handle assembly connected to an amplifier assembly). In such embodiments, the amplifier assembly is configured to transduce energy derived from, for example, such a pressure source to energy transmitted to such a catheter and tissue-engaging element for applying energy (e.g., pressure) to, for example, a distal balloon or heart-tissue-conforming element present at a distal region of such catheter; i.e., to repeatedly pressurize and inflate such balloon or aspects of such heart-tissue- conforming element.

[0054] In embodiments, an amplifier assembly comprises a diaphragm sealed between a proximal nose and a distal waveguide. In embodiments, an amplifier assembly comprises a diaphragm held in compression between a proximal nose and a distal waveguide. In embodiments, the diaphragm separates a proximal chamber, present in the proximal nose, from a distal chamber, present in the distal waveguide. In embodiments, the proximal chamber is defined by a first volume between the diaphragm and the distal face of the proximal nose. In embodiments, the distal chamber is defined by a second volume between the diaphragm and the proximal face of the distal waveguide.

[0055] Amplifier assemblies according to the present invention are configured to receive a first pulsatile energy from an energy source, such as a potential source, e.g., a pulse generator, transducing it to a second pulsatile energy that may be propagated along the length of the amplifier assembly, e.g., along a fluid, e.g., liquid, passageway thereof, ultimately, to, for example, a distal balloon or other tissue-engaging element. As the amplifier assembly transduces the first pulsatile energy to a second pulsatile energy, it changes the form of the pulsatile energy in some way. Examples of changes to the form of energy that may be made by the amplifier assembly include, but are not limited to: gas pressure and/or flow to liquid pressure and/or flow, mechanical potential and/or kinetic energy to fluid pressure and/or flow, optical potential and/or kinetic energy to fluid pressure and/or flow, electric field potential and/or kinetic energy to fluid pressure and/or flow, magnetic potential and/or kinetic energy to fluid pressure and/or flow, and the like. For example, where the first pulsatile energy is a pneumatic first pulsatile energy, the amplifier assembly may be configured to transduce the pneumatic first pulsatile energy to a second hydraulic pulsatile energy that may be propagated from the proximal end of the amplifier assembly to the distal end of the amplifier assembly, which is an example of gas to liquid transduction of the pulsatile energy. In some instances, the amplifier assembly propagates the second pulsatile energy from the proximal to distal end of the amplifier assembly with little, if any attenuation, where the magnitude of any attenuation, if present, does not exceed 30% reduction, and in some instances does not exceed 5%, for example.

[0056] Similarly, amplifier assemblies according to the present invention are further configured to receive first static energy from an energy source, such as a potential source, and transducing it to a second static energy that may be propagated along the length of the amplifier assembly, e.g., along the fluid, e.g., liquid, passageway thereof, ultimately, to a distal balloon. By static energy, it is meant, for example, the application of a first pressure, such as the application of pneumatic energy maintained for a specified period of time. That is, amplifier assemblies may be configured to receive a first pressure applied to an amplifier assembly for a specified period of time.

[0057] Amplifier assemblies according to embodiments of the present invention are configured to be operably connected to a handle assembly, which ultimately comprises, or is itself connected to, a source of energy for supplying a first pulsatile energy or a first static energy. An amplifier assembly may operably connect to a handle assembly utilizing any of a variety of standard connectors well-known in the art to achieve a quick, reliable, and repeatable connection of the handle assembly to the amplifier assembly. Examples of such standard connectors include, for example, a press fit connector, latch connector, screw connector, threaded connector, magnetic connector, push-to-connect connector, Yor-lock connector, claw clamp connector, gasket connector, socket connector, flanged connector, cam-and-groove socket, quick-connect connector and the like, where aligners or detents may be employed, as desired, to provide for a connection that repeatably and accurately positions the amplifier assembly in relation to the handle assembly and/or electrical connectors, i.e., electrical connectors of the handle assembly.

[0058] Amplifier assemblies may be configured to be reusable or single use, as desired. In cases where the amplifier assembly (or aspects thereof) is reusable and could contact a patient area, such assembly can be configured to be covered in a disposable, sterile sleeve or bag such that the amplifier assembly may be used while not contaminating a sterile field of an operating room.

Diaphragm

[0059] As described above, amplifier assemblies of embodiments of the present invention comprise a diaphragm sealed between the proximal nose and the distal waveguide separating a proximal chamber from a distal chamber. In some cases, amplifier assemblies of embodiments of the present invention comprise a diaphragm compressed between the proximal nose and the distal waveguide thereby sealing a proximal chamber from a distal chamber. In embodiments, a proximal nose is located on a relatively proximal region of an amplifier assembly and a distal waveguide is located in a relatively distal region of the amplifier assembly such that a distal face of the proximal nose is substantially opposed to a proximal face of the distal waveguide. In embodiments, the proximal chamber is defined by a first volume between the diaphragm and the distal face of the proximal nose. In embodiments, the distal chamber is defined by a second volume between the diaphragm and the proximal face of the distal waveguide. The diaphragm is configured to translate between a distal face of the proximal nose and a proximal face of the distal waveguide. As described herein, the diaphragm is configured to translate as such without producing strain on the diaphragm.

[0060] As described above, the diaphragm may be sealed between the proximal nose and the distal waveguide separating a proximal chamber from a distal chamber. In some cases, the diaphragm may be compressed between the proximal nose and the distal waveguide thereby sealing a proximal chamber from a distal chamber. In embodiments, diaphragms may comprise an outer ring or retaining feature configured to seal an interface between the proximal nose and the distal waveguide. In some cases, such outer ring or retaining feature is an O-ring, such as a polymer O-ring, attached to or molded onto the diaphragm. In other embodiments such interface may be sealed by employing a clip.

[0061] In other embodiments, the diaphragm comprises an outer ring or retaining feature that is a circumferential protrusion attached to or molded onto the diaphragm and is configured to, as reviewed above, enable the diaphragm to maintain its seal while translating between the distal face of the proximal nose and the proximal face of the distal waveguide. That is, the diaphragm may comprise a circumferential protrusion shaped so that when the diaphragm is translated in either proximal or distal directions, the protrusion reinforces the diaphragm seal, for example, on a side opposite to the direction in which the diaphragm translates. In some cases, the circumferential protrusion is a T-shaped edge or wedge.

[0062] In embodiments, the outer ring or retaining feature or circumferential protrusion may be separate from or co-molded with the rest of the diaphragm. Such outer ring or retaining feature or circumferential protrusion of the diaphragm may have any convenient geometry, as desired, such as a circumferential protrusion in an exterior position of the diaphragm that is substantially T-shaped, circular or wedge-shaped or has a cross- sectional geometry sufficient for mechanical retention of a gasket or ring seal subjected to mechanical, pneumatic or hydraulic stress or the like. In embodiments, the outer ring or retaining feature or circumferential protrusion is shaped to fit within corresponding grooves of the proximal nose and the distal waveguide. Each of these grooves may comprise a lip that compresses the relatively softer diaphragm material. The interaction between the grooves and the outer ring or retaining feature or circumferential protrusion of the diaphragm creates both an axial seal and a radial support zone to prevent pull-out of the diaphragm during pulsing, i.e., translation of the diaphragm in proximal and distal directions.

[0063] To further reduce the pull-out force during pulsing, the diaphragm may be configured to translate between the distal face of the proximal nose and proximal face of the distal waveguide without producing strain on the diaphragm. For example, in embodiments, to further reduce the pull-out force during pulsing, additional material may be built into the diaphragm to allow it to move axially (i.e., translate in distal and proximal directions) without creating significant pull-out force at the sealing edge of the diaphragm (e.g., an outer circumference of the diaphragm). As described herein, such additional material may be built into the diaphragm via accordion-like bellows such that the bends and folds of the bellows provide material for the center of the diaphragm to translate without significantly increasing the radial force at the exterior of the diaphragm, for example. That is, the diaphragm is configured to translate between the distal face of the proximal nose and proximal face of the distal waveguide without producing significant strain on the diaphragm. Because of such reduction in radial stress, the force pulling the diaphragm at its edge, i.e., outer circumference, is reduced, thereby mitigating leakage (breaking a seal of the proximal or distal chambers, for example) or pullout conditions.

[0064] It is contemplated that some embodiments utilize a diaphragm configured to translate proximally and distally without producing strain on the diaphragm, e.g., a diaphragm with additional material such as folds or bellows, functions as a living hinge. Diaphragm shapes can be generated via conventional molding techniques, for instance, or can be created via stamping, molding or heat stamping. Residual stress can be built into the design of the diaphragm such that when the diaphragm is translated axially due to an incoming pressure pulse, the diaphragm is stretched to a specified, desired degree such that, for example, the diaphragm is caused to return to its initial state, e.g., a neutral state or center position. This residual stress in the diaphragm forces the diaphragm to its initial position, thereby creating a vacuum or negative pressure in the distal chamber during the “off” part of the cycle.

[0065] Further, configuring the diaphragm to translate proximally and distally without producing strain on the diaphragm (e.g., utilizing a bellows configuration) of the diaphragm allows the diaphragm to continuously expand to meet the volume needs of, for example, an expanding distal balloon operably connected to the amplifier assembly, receiving fluid displaced by the diaphragm from the distal chamber, for example. In embodiments, the diaphragm is configured to be a living hinge (i.e., the diaphragm is configured to translate proximally and distally without producing strain, or substantial strain, on the diaphragm) that operates in the low elastic range of the diaphragm material, as opposed to utilizing a flat sheet for a diaphragm where relatively significant radial stress would be imparted on the diaphragm wall. In embodiments, diaphragm materials are selected such that they operate in the low elastic range when formed into the desired diaphragm configuration. Such configuration of diaphragms in the present invention increases the reliability of the diaphragm when exposed to high pressure fluids.

[0066] As described above, in embodiments, the diaphragm is configured to occupy different positions between the distal face of the proximal nose and the proximal face of the distal waveguide. In embodiments, the diaphragm is further configured to translate between such different positions without producing strain on diaphragm material. As the diaphragm translates back and forth between the distal face of the proximal nose and the proximal face of the distal waveguide, the diaphragm may take on different shapes to conform to the different positions, e.g., may unfold itself making additional diaphragm material available to accommodate the different positions without producing strain on the diaphragm. The diaphragm may be configured such that it can conform to, i.e., cover or lay flat over, the distal face of the proximal nose in a proximal position of the diaphragm and to the proximal face of the distal waveguide in a distal position of the diaphragm. In embodiments, the diaphragm comprises a shape that conforms to the distal face of the proximal nose in a proximal position of the diaphragm and to conform to the proximal face of the distal waveguide in a distal position of the diaphragm. For example, in some cases, the diaphragm comprises folds or pleats or pleated bellows. That is, the diaphragm may be shaped or otherwise configured so that the additional material is made available (i.e., unfolded) when the diaphragm is extended into relatively more proximal or more distal positions. Such diaphragms may be further configured so that such additional material is re-folded onto itself when the diaphragm returns to a relatively neutral position.

[0067] In some embodiments, the diaphragm comprises a shape that, when the diaphragm is substantially fully extended, fits within indentations of the distal face of the proximal nose and within indentations of the proximal face of the distal waveguide. For example, the diaphragm may comprise folds located on the diaphragm such that the additional material unfolds into corresponding curvatures or other shapes of the distal face of the proximal nose or the proximal face of the distal waveguide, in each case configured to receive such material additional material of the diaphragm. That is, the linear length of the diaphragm is configured such that in its expanded position, either proximally or distally, it conforms to the surface of the distal face of the proximal nose or to the surface of the proximal face of the distal waveguide such that there is minimal unused space or trapped gas that can lead to a decreased efficiency in the maximum pulse delivery.

[0068] As described above, the diaphragm is configured to translate between the distal face of the proximal nose and proximal face of the distal waveguide without producing strain on the diaphragm. By not producing strain on the diaphragm, it is meant, for example, without producing tension on the diaphragm or without stretching diaphragm material or without resistance from diaphragm material or without applying stress to diaphragm material. In embodiments, without producing strain on the diaphragm means without producing substantial or material or significant or an undesired or unanticipated amount of strain on the diaphragm, e.g., such as strain that may be sufficient to cause the diaphragm to leak from, or pull out of its position, between the proximal nose and the distal waveguide.

[0069] As described above, the diaphragm separates the proximal and distal chambers and is configured to translate in response to a first pulsatile energy and, in doing so, produce a second pulsatile energy in the distal chamber of the amplifier assembly. The dimensions of the diaphragm may vary, where in some instances the diaphragm has an area ranging from, 100 mm² to 5000 mm², such as 500 mm² to 2000 mm², or 400 mm² to 800 mm². The diameter of the diaphragm when in its fully neutral or folded state may vary, where in some instances the diaphragm has a folded diameter ranging from 10 mm to 75 mm, such as 20 mm to 50 mm, or 10 mm to 40 mm. The diaphragm may be fabricated from any convenient material, where in some instances the material is substantially not elastic, i.e., not pliant. In some cases, the material has a hardness ranging from Shore 10A to Shore 90A, or Shore 30A to Shore 90A, such as Shore 50A, and a thickness between 0.5 mm to 5mm, such as 1 .0 mm to 2.5 mm. Examples of suitable diaphragm materials include, but are not limited to: silicones, rubbers, urethanes, synthetic or natural polymers, elastomers, fabrics, woven and non-woven fibers and the like. In some cases, diaphragm material may be strengthened by adding a reinforcing component, such as inlaid fibers, surface coatings, adhesives, internal or external structures, hardware, hinges, wires, cables, or additional layers of the same composition, e.g., additional layers of a material. Where desired, a biasing component, such as a spring, may be provided to provide for a default or baseline diaphragm position and/or shape and/or configuration. For example, a spring may be provided on the distal chamber side of the diaphragm, which urges the diaphragm back to an initial position and/or shape and/or configuration when force is removed from the proximal chamber side of the membrane.

[0070] As reviewed above, in embodiments, a diaphragm is a flexible impermeable membrane that converts pulsatile pneumatic pulses (i.e., of the proximal chamber) to pulsatile fluid pulses (i.e., of the distal chamber). A diaphragm, in an embodiment, also separates the proximal chamber (i.e., pneumatic chamber) from the distal chamber (i.e., a distal fluid chamber). Further, the diaphragm is configured to ensure a proper and reliable seal between the internal chambers and atmosphere.

[0071] In embodiments, applying pulsatile energy between the proximal chamber and the distal chamber requires longitudinal motion of the diaphragm from a proximal position to distal position (i.e., translating the diaphragm distally and proximally). Diaphragms of the present invention are configured such that such longitudinal motion causes at least two effects: (1 ) applying a “water hammer” effect of pulsatile energy to a fluid in the distal chamber and, ultimately to a tissue-engaging element operably connected to an amplifier assembly, such as a distal balloon ultimately operably connected to the amplifier assembly, and also to surrounding tissue and (2) continuously increasing the volume transmitted to such distal tissue-engaging element, such as increasing the volume in a distal balloon, as tissue surrounding the tissue-engaging element, e.g., distal balloon, is softened (i.e., as calcium deposits are fatigued and/or cracked).

[0072] As reviewed above, amplifier assemblies of embodiments of the present invention comprise a proximal nose, comprising a distal face. In embodiments, the amplifier assembly is configured so that the diaphragm is sealed between the proximal nose and the distal waveguide separating a proximal chamber from a distal chamber, and further configured such that the diaphragm translates between the distal face of the proximal nose and proximal face of the distal waveguide. In embodiments, the diaphragm is compressed between the proximal nose and the distal waveguide, thereby sealing the proximal chamber from the distal chamber. In embodiments, the diaphragm translates between the distal face of the proximal nose and proximal face of the distal waveguide without producing strain on the diaphragm.

[0073] The form of the proximal nose may vary in shape. In some instances the proximal nose is substantially cylindrical. In some cases, the shape of the proximal nose comprises a collar on a relatively proximal side and/or another collar on a relatively distal side. In certain cases, the proximal nose comprises a center region shaped to form a proximal chamber on one side, a relatively distal side and, on another, relatively proximal side, opposite to that, a proximal interface with a high-pressure connector. In embodiments, the proximal nose may have any convenient diameter, such as a diameter ranging from 2.5 mm to 100 mm, such as 5 mm or 50 mm and any convenient length (i.e., length along the long axis of the amplifier assembly), such as a length ranging from 50 mm to 500 mm, such as 100 mm or 250 mm. In embodiments, the proximal nose may be formed from any convenient material; for example the proximal nose may be a molded plastic, rubber, ceramic or metal, in some cases, with dissimilar materials molded into, mechanically attached or adhered to the material of the proximal nose, e.g., molded into, mechanically attached or adhered to plastic, metal or rubber ends of the proximal nose. When present, the dissimilar material can be over molded to associate or join or combine the dissimilar material with the material of the proximal nose. For example, the dissimilar material can be over molded such that a cooling plastic element shrinks onto a metal insert no matter the direction of cooling.

[0074] In embodiments, the proximal nose is shaped to form a proximal chamber that is a geometrical cavity within the proximal nose, in which high-pressure pneumatic fluid, e.g., high-pressure gas such as air or CO2, expands as it exits a high-pressure connector (as described herein) and impacts the proximal side of the diaphragm. This interaction causes the diaphragm to displace distally and to create a pneumatic pulse. The shape of the proximal chamber (also, in embodiments, referred to as a pneumatic amplifier cavity) minimizes the volume of pneumatic pulse such that pressure can be ramped up rapidly while maximizing the area (i.e., the area of the diaphragm) subjected to the pressure pulse. This enables an efficient pulse to occur with minimal fluid (e.g., high- pressure gas) waste. Further, the geometry of the proximal chamber prevents oversaturation and maintains a linear output of frequency and displacement sensors during use of the amplifier assembly.

[0075] In embodiments, the proximal nose is shaped such that it comprises a groove, such as a ring (i.e., a ring around an outer circumference) that is a toroidal groove that can receive a circumferential protrusion of the diaphragm described herein (e.g., in some cases, such groove is configured to receive an O-Ring attached to the diaphragm). The groove may have radially disposed recessed retaining geometry that controls the location and deformation/compression of the circumferential protrusion of the diaphragm (e.g., an O-ring attached thereto). Once the circumferential protrusion of the diaphragm is seated, the groove constrains the diaphragm from being pulled out of the groove and maintains the seal when the diaphragm is cycled through various pressures and displacements.

[0076] In some cases, the proximal nose comprises a proximal interface located at a proximal region of the proximal nose. By proximal interface, it is meant, a proximal side or face of the proximal nose. In some instances, the proximal interface is configured to interface with a handle assembly. In embodiments, the proximal interface comprises a high-pressure connector; i.e., a connector fluidically connected to the proximal chamber such that the amplifier assembly can receive energy, e.g., high pressure fluid, such as high-pressure air or CO2, or a first pulse energy or pneumatic pulsatile energy or static energy, generated by an energy source operably connected to the amplifier assembly through the handle assembly, which handle assembly interfaces with the amplifier assembly at the proximal interface via the high-pressure connector.

[0077] In embodiments, the high-pressure connector is substantially cylindrical. In some embodiments, the connection between the amplifier assembly and a handle assembly is achieved through a high-pressure connector that is a connector tube or nozzle that is either part of the manufactured proximal nose or is added to the proximal nose, i.e., is a separate component. In the case where the high-pressure connector is added to the manufacturing of the proximal nose, the high-pressure connector material can be a metal, i.e., a metal part molded into plastic of the proximal nose, such as stainless steel, coated or uncoated aluminum, plated or un-plated brass, copper or a similar corrosion-resistant material. While the dimensions of the high-pressure connector may vary as desired, in some instances the high-pressure connector has an outer diameter ranging from 1 mm to 30 mm, such as 3 mm to 8 mm and inner diameter ranging from 1 mm to 30 mm, such as 2 mm to 7 mm. In such instances where the proximal nose has a high-pressure connector, the high-pressure connector may have a length ranging from 1 mm to 50 mm, such as 3 mm to 10 mm.

[0078] In instances where the proximal nose includes a high-pressure connector, the proximal chamber of the proximal nose is fluidically coupled to the high-pressure connector. In such instances, the junction between the high-pressure connector and the proximal chamber may include a nozzle and/or diffuser, which, in some cases, may be formed geometrically by the proximal nose. In such instances, the nozzle or diffuser may act to increase or decrease velocity of the flow of fluid (e.g., high-pressure gas) therein at the expense of fluid pressure. With such increase or decrease of velocity of the flow of fluid, characteristics of the energy conversion (i.e., between a first energy applied to the proximal chamber and a second energy applied to the distal chamber; a first pulse energy to a second pulse energy) may be improved, such as a ramp up time or a smoothness of energy conversion. In cases of pneumatic flow, the speed of the gas may be high enough to induce compressible fluid phenomena such as in sonic or supersonic flows. In such cases, specialized flow nozzles such as a convergent-divergent nozzle may be used to optimize flow velocity.

[0079] In embodiments, the high-pressure connector comprises an O-ring groove configured to receive an O-ring. Such groove and associated O-ring may be included to create a reliable seal on the high-pressure connector, i.e., between the high-pressure connector and a handle assembly. The O-ring groove may be present in a proximal region of the high-pressure connector and may comprise a grooved retaining feature for one or more O-Rings. Such groove may be present in a proximal region of the high- pressure connector and may comprise any convenient dimensions, i.e., any convenient depth and width, and such may vary. As such, any convenient O-ring, e.g., a polymer O- ring, may be installed based on the corresponding dimensions of the O-ring groove. In embodiments, the high-pressure connector and O-ring, which is retained on or within the high-pressure connector, is inserted into a mating socket, i.e., of a handle assembly, which creates a reliable, high-pressure seal. [0080] In other embodiments, such a reliable high-pressure seal is created via a face seal where a sealing gasket is pushed against a smooth face, e.g., of a handle assembly, to create a reliable seal. Additional embodiments may include non-polymer O-Rings or gaskets, tube or pipe compression/expansion fittings, push-to-connect pneumatic plugs and socket receivers, medical Luer type connectors or other connectors and/or combinations thereof.

[0081] In some embodiments, the proximal interface comprises an alignment feature, such as a keyed face. Such an alignment feature, such as a keyed face, may be used to align the proximal interface of the proximal nose with a handle assembly, when operably connecting the two. For example, a keyed face may control rotational, axial, and radial position of the amplifier assembly with respect to a mating receptacle of a handle assembly. Further, by keyed face, it is meant that the proximal interface comprises one or more features with, in some cases, rotational asymmetry such that the keyed face allows the proximal interface to interface with a handle assembly in only one rotational orientation (i.e., around the long axis of the amplifier assembly or the axis normal to the handle assembly). The keyed face may be used to align the proximal nose with a handle assembly such that elements of each assembly are aligned when operably connected. For example, the amplifier and handle assemblies may require alignment such that electrical connectors on each assembly properly align with each other. Any convenient keying mechanism may be employed on the proximal interface of the proximal nose, such as, for example, a grooved detent, an asymmetrical channel, an oblong shape and a rectangular prism. Such elements may comprise any convenient dimensions as desired. Further, internal features such as a slot or groove may be used to further constrain the position of interlocking features of the amplifier assembly. A backstop element may be used to set the axial depth of the amplifier assembly in a receptacle of a handle assembly. These features may act solely or in unison to constrain rotational, axial, and radial location of the amplifier assembly in a receptacle of the handle assembly.

[0082] In certain embodiments, the handle assembly and amplifier assembly may comprise one or more sensors configured to confirm that the amplifier assembly and handle assembly are connected. In some cases, such sensor is configured to indicate that the handle assembly and amplifier assembly are operably connected, or are connected in an expected or specified orientation or configuration. In some cases, the handle assembly and amplifier assembly may be configured to comprise a displacement sensor configured to confirm that a distance between and/or orientation of the handle assembly and amplifier assembly is as expected or as specified. The handle assembly and amplifier assembly may comprise a Hall sensor configured to act as a connection/disconnection switch. In certain cases, the Hall sensor may comprise a magnet located on a handle assembly and a probe located on the amplifier assembly or vice versa. In other cases, a magnet may be located on each of the handle and amplifier assemblies and a probe may be located on either the handle or amplifier assembly. When present, a Hall sensor may be calibrated to measure a distance between aspects of the handle and amplifier assemblies, such as, for example, a distance between the distal interface of the handle assembly and the proximal face of the amplifier assembly. In embodiments, the handle assembly is configured with one or more interlocks such that energy cannot be transmitted (e.g., to the distal interface of the handle assembly) when a Hall sensor fails to confirm that the handle and amplifier assemblies are operably connected.

[0083] In embodiments, the proximal nose is shaped to include a flexible electronics bay on which aspects of an electrical assembly, as described herein, is mounted. In some cases, the proximal nose is further shaped to include a guide for attaching aspects of an electronics assembly. That is, in embodiments, the flexible electronics bay and guide locates an electronics assembly or aspects thereof, such as a flexible printed circuit board, such that a repeatable connection can be made between electronic connectors (i.e., electrical connectors) of the amplifier assembly and corresponding connectors of a handle assembly. Such a guide section of the proximal nose can be used to locate and connect aspects of an electronics assembly, such as a flexible printed circuit board, during assembly and use such that, for example, a flexible circuit board or other components are not pinched or damaged.

[0084] In embodiments, the proximal nose may be shaped to include a housing retaining feature. Such feature locates one or more aspects of a housing (as described herein) with respect to the proximal nose. Such feature may also be used to lock, i.e., retain, the housing into a final location. In some embodiments, the housing retaining feature may be a mating groove or ridge, a nub, or a clearance, press fit, or pin/screw hole or the like. In other embodiments, the proximal nose is configured to include a distal waveguide locating guide. When present, the distal waveguide locating guide is a feature of (e.g., the proximal nose is shaped to include such a locating guide) the proximal nose that locates the distal waveguide during assembly and ensures that the distal waveguide is assembled, vis-a-vis the proximal nose, in a desired location and orientation.

[0085] In some cases, the proximal nose is further configured to include a distal waveguide retaining zone or retaining features. When included, such a retaining zone is a set of features that ensures proper compression loading of the distal waveguide and diaphragm during assembly with the proximal nose. Such features further fix the distal waveguide in place once positioned in the desired position and/or orientation. In some embodiments, the distal waveguide retaining zone is a set of holes that receive hardware, such as pins, screws, bolts or the like, configured to control and lock the compression distance of the amplifier assembly, i.e., to control and lock in place the position of the proximal nose, distal waveguide and diaphragm compressed therebetween. In other embodiments, the distal waveguide retaining zone is a set of deflecting and interlocking features that, once snapped into, inhibits removal of the distal waveguide from the proximal nose (and diaphragm compressed therebetween. Such other features may comprise, for example, a zip tie-like mechanism or other one-way ratchet mechanism or the like. In other embodiments, the distal waveguide retaining zone represents a location for heat staking, thermal deformation, laser welding or ultrasonic welding to occur, i.e., to fix the distal waveguide in a position relative to the proximal nose with the diaphragm compressed therebetween. In other embodiments, the retaining features may comprise features positioned at a selected location of the proximal nose corresponding to a specific location of the distal waveguide when the proximal nose and distal waveguide are brough together, such as at a location corresponding to a relatively distal position of the distal waveguide or a relatively proximal position of the distal waveguide or combinations thereof. Such retaining features may comprise, for example, any convenient adhesive, such that the retaining features distribute compression load from the distal waveguide to the proximal nose. In certain embodiments, the retaining features comprise potting a region, such as a distal region or a proximal region, of the assembly with an adhesive. Such adhesive potting may in part distribute a compression load from the distal waveguide to the proximal nose.

[0086] As described herein, proximal noses of interest, as well as handle assemblies operably connected thereto, are capable of receiving fluid, in particular fluid that is subjected to pressure oscillations during use. In embodiments, a fluid (e.g., a gas) is introduced into the proximal nose via a handle assembly and such fluid is subjected to pressure oscillations. Any convenient fluid, or evacuated absence of fluid/gas, such as vacuum or very low-pressure fluid, may be applied, and such may vary. When such fluid is a gas, gases of interest comprise air or CO2 or Nitrogen, Helium, Nitrous Oxide, Argon, Helium, water vapor, phase changing refrigerant, coolant, where, in each case, the gas may be sterile.

Distal Waveguide-.

[0087] As reviewed above, amplifier assemblies of embodiments of the present invention comprise a distal waveguide, comprising a proximal face. In embodiments, the amplifier assembly is configured so that the diaphragm is sealed between the proximal nose and the distal waveguide separating a proximal chamber from a distal chamber. In other embodiments, the amplifier assembly is configured so that the diaphragm is compressed between the proximal nose and the distal waveguide thereby sealing a proximal chamber from a distal chamber, and further configured such that the diaphragm translates between the distal face of the proximal nose and proximal face of the distal waveguide.

[0088] The form of the distal waveguide may vary in embodiments, where in some instances the distal waveguide is substantially conical or substantially cylindrical. In some cases, the shape of the distal waveguide comprises a relatively proximal portion that is substantially conical and a relatively distal portion that is substantially cylindrical. In certain cases, the distal waveguide comprises a region shaped to form a distal chamber on a relatively proximal side opposite, and fluidically connected to, a catheter interface on a relatively distal side. In embodiments, the distal waveguide may have any convenient diameter, i.e., maximum diameter, such as a diameter ranging from 10 mm to 100 mm, such as 25 mm or 50 mm and any convenient length (i.e., length along the long axis of the amplifier assembly), such as a length ranging from 25 mm to 250 mm, such as 50 mm or 75 mm. In embodiments, the distal waveguide may be formed form any convenient material; for example the distal waveguide may be a molded plastic, rubber, ceramic or metal, in some cases, with dissimilar materials molded into, mechanically attached or adhered to the material of the distal waveguide, e.g., molded into, mechanically attached or adhered to plastic, metal or rubber ends of the distal waveguide.

[0089] Embodiments of the distal waveguide are shaped to include a fluid pathway that is initiated at a distal side of the diaphragm and includes the distal chamber of the distal waveguide as well as a catheter interface (as described herein). Such fluid pathway, after exiting the distal waveguide, may continue through flexible tubing, a Y-hub, a catheter and, ultimately, a balloon. This fluid pathway is filled with fluid (e.g., saline, salinecontrast, or other fluid or fluid mixture commonly used in interventional practice, i.e., interventional cardiology) to create a fluid column. This fluid column is pulsed via hydraulic shock or the water hammer effect, in which the fluid transmits a pressure wave from a distal end of the distal waveguide, ultimately, to a tissue-engaging element, such as a distal balloon, which is operably connected to the amplifier assembly via the catheter. A volume change in such a distal balloon subsequently occurs to create the pulsatile effect. As calcium cracks and the diseased vessel becomes more compliant, the diaphragm of the amplifier assembly delivers more fluid volume to the tissue-engaging element, e.g., a distal balloon.

[0090] In some embodiments, the distal waveguide comprises a funnel-like geometry configured to guide a pressure wave into a fluid channel. Such a configuration of a distal waveguide also helps ensure that a distal side of the diaphragm is supported in cases where there is a rapid expansion or burst of a balloon operably connected to the amplifier assembly and prevents blowout. In embodiments, an internal bell jar shape of the distal waveguide provides a structured, maximum volumetric expansion that limits the displacement and elastic stress on the diaphragm. The distal waveguide may be configured to, e.g., may comprise an internal shape that, helps ensure a smooth flow vector transmission from the diaphragm to the fluid channel, i.e., catheter interface, with minimal turbulence of such flow.

[0091] Similar to what is described herein with respect to the proximal nose, distal waveguides may comprise or may be shaped to include a groove that is a ring (i.e., a ring around an outer circumference) that is a toroidal groove that can receive a circumferential protrusion of the diaphragm described herein (in some cases, such groove is configured to receive an O-Ring attached to the diaphragm). The groove has radially disposed recessed retaining geometry that controls the location and deformation/compression of the circumferential protrusion of the diaphragm (e.g., an O-ring attached thereto). Once the circumferential protrusion of the diaphragm is seated in such groove of the distal waveguide (and corresponding groove of the proximal nose), the groove constrains the diaphragm from being pulled out of its position and configuration compressed between the distal waveguide and proximal nose and maintains the seal when the diaphragm is cycled throughout various pressures and displacements.

[0092] In one embodiment, the distal waveguide comprises a section that has a funnellike geometry that guides the pressure wave into the fluid channel. The distal waveguide also ensures that the distal part of the diaphragm is supported in cases where there is a rapid expansion or burst of the balloon and prevents blowout. The distal waveguide shape ensures a smooth flow vector transmission from the diaphragm to the fluid channel with minimal turbulence of the flow.

[0093] In embodiments, the distal waveguide comprises a catheter interface located at a distal region of the distal waveguide. By catheter interface, it is meant an interface offering a fluidic connection to the distal waveguide and configured to attach to, for example, a catheter, i.e., a catheter assembly. The distal waveguide is configured such that fluid, e.g., saline, present in the distal chamber may be urged by the diaphragm through the catheter interface to, for example, a distal balloon or other tissue-engaging element operably connected to the output of the amplifier assembly. That is, when the amplifier assembly receives energy, e.g., a first pulse energy or pneumatic pulsatile energy or static energy, generated by an energy source operably connected to the amplifier assembly and transduces such energy into a second pulse energy or static energy within the distal chamber, such second energy or second pulse energy (e.g., a high-pressure fluid, such as high-pressure fluid comprising saline) may be transmitted from the distal chamber to the catheter interface. In embodiments, the catheter interface is in fluidic communication with the distal chamber. In some cases, the catheter interface comprises a Luer lock, such as a floating Luer lock, for example. While the dimensions of the catheter interface may vary as desired, in some instances the catheter interface has an outer diameter ranging from 2 mm to 20 mm, such as 5 mm to 10 mm and inner diameter ranging from 1 mm to 10 mm, such as 4 mm to 8 mm. In such instances where the distal waveguide has a catheter interface, the catheter interface may have a length ranging from 2.5 mm to 25 mm, such as 4 mm to 12 mm.

[0094] Embodiments of distal waveguides further comprise (i.e., may be shaped to include) a retaining zone that is a zone on, for example, a distal region of the distal waveguide configured to retain the distal waveguide vis-a-vis (e.g., within or compressed against) the proximal nose after an appropriate compression depth has been set (i.e., an appropriate compression of the diaphragm between the proximal nose and distal waveguide). In some embodiments, the retaining zone is used to distribute load from pulsatile pressure waves of the amplifier assembly across an entire distal surface of the distal waveguide. In other embodiments, the retaining zone is a location of heat staking, ultrasound welding, potting or other technique for combining the proximal connector nose and distal waveguide.

[0095] In some embodiments, the amplifier assembly further comprises pins, such as steel pins, that are retaining pins configured to hold the distal waveguide in sealing engagement with the diaphragm and the proximal nose. In embodiments, the distal waveguide is shaped so that pins can be placed in a distal side of the distal waveguide to apply force in a relatively proximal direction. In embodiments, such pins may be placed through holes or slots on a distal region of the proximal nose, i.e., a distal collar of the proximal nose, such that the pins rest against a distal side of the distal waveguide.

[0096] In embodiments, the distal waveguide is shaped to include a guide for attaching aspects of an electronics assembly. That is, in embodiments, a flexible electronics guide locates and/or protects an electronics assembly or aspects thereof, such as a flexible printed circuit board, such that connections can be made to different components of the amplifier assembly and/or a repeatable connection can be made between electrical connectors of the amplifier assembly and corresponding connectors of a handle assembly. Such a guide section of the distal waveguide can be used to locate and connect and/or protect aspects of an electronics assembly, such as flexible electronics, during assembly and use such that, for example, a flexible circuit board or other components are not pinched or damaged.

[0097] As described herein, the distal waveguide may be operably connected, ultimately, to a distal balloon or other tissue-engaging element via, for example, a Luer lock connected to flexible tubing, a Y-hub connector and one or more catheters. In embodiments, the Luer lock section connects to flexible tubing that connects to a Y-hub on a catheter. Such components, in part, act as strain relief between the amplifier assembly and the catheter. Such components are configured to transmit pulsatile pressure waves between the amplifier assembly and a catheter and ultimately to a distal balloon or other tissue-engaging element.

[0098] As described herein, distal waveguides of interest, as well as catheters operably connected thereto, are capable of receiving fluid, in particular fluid that is subjected to pressure oscillations during use. In embodiments, a fluid (e.g., a liquid) is introduced into the distal waveguide, e.g., via a microcatheter or other assembly fluidically connected to the distal waveguide, and such liquid is subjected to pressure oscillations. Any convenient fluid may be applied, and such may vary. When such fluid is a liquid, liquids of interest comprise water or a saline solution with or without a contrast or other radiopaque liquid or fluorocarbons or perfluorocarbons, where, in each case, the liquid may be sterile. Other liquids of interest include iodine-based fluids, barium-sulfate, gadolinium, or other radio-contrast agents, where, in each case, the liquid may be sterile.

Electrical Assembly:

[0099] In embodiments, amplifier assemblies further comprise an electrical assembly (also referred to as an electronics assembly) integrated into one or more of the proximal nose, the distal waveguide and the diaphragm. Electrical assemblies may be configured to perform various functions, as desired, including, for example, powering various sensors throughout or external to the amplifier assembly, controlling such sensors, receiving data from such sensors, recording and/or transmitting, e.g., wirelessly transmitting, such data to another location, controlling various aspects of the amplifier assembly or aspects external to the amplifier assembly and/or storing information about the amplifier assembly or a handle assembly to which it is connected or other aspects of the system to which the amplifier assembly is connected, for example.

[0100] In some cases, the electrical assembly comprises a controller programmed to perform self-check routines confirming the safety of the amplifier assembly and/or selfdiagnostic routines, for example. In an embodiment, the electrical assembly is a flexible printed circuit board and is configured to perform several functions including, for example, creating an electrical connection to a handle assembly, using sensor readings to measure pressure of fluid in the distal chamber, using sensor readings to measure a position of the center of the diaphragm, storing catheter, balloon (or other tissue-engaging element) and/or other treatment specific information in a memory or reading such information therefrom.

[0101] The electrical assembly may vary, and in some instances may include circuitry and/or memory. When present, the memory may store a variety of different types of information, including but not limited to: information about the amplifier assembly and/or components thereof or components to which it is operably connected, e.g., a handle assembly or, e.g., a distal balloon (or other tissue-engaging element), or information related thereto, such as an expiration date, batch number, balloon size (e.g., balloon diameter and length), balloon rated burst and nominal pressure, cycle limit (e.g., number of allowable cycles the balloon is rated for), and cycles used for, allowable pulse frequency or duration, previous use, balloon reference pressure-volume curve, and/or indication for use, etc.

[0102]The electrical assembly may be present in any convenient configuration, such as a printed circuit board, including a flexible printed circuit board. In some cases, the electronic assembly may transmit data wirelessly, such as through Bluetooth RF. In instances, the electrical assembly comprises one or more microprocessors, such as one or more microcontrollers or the like. Microprocessors of interest include commercially available processors, such as, for example, a general-purpose or other specific-purpose processor, controllers, microcontrollers, application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), dedicated digital and/or analog circuitry or other logic circuit or the like. Such microprocessors may comprise one or more memories. Memories of interest include commercially available memories, such as volatile and non- volatile memory storage chips, devices or systems. Electrical assemblies may be mounted on the proximal nose or the distal waveguide or other aspects of an amplifier assembly, as desired.

[0103] The electrical assembly, when present, may further include a connector for operably connecting the electrical assembly to a handle assembly. In embodiments, the electrical assembly comprises a plurality of electrical connectors integrated into the proximal interface. The number of electrical connectors may vary as desired. Any convenient form of electrical connectors may be employed. For example, the proximal interface may be configured such that the electrical connectors make electrical connections by connecting elements that are oriented perpendicular to a long axis of the amplifier assembly. In some cases, the electrical connectors comprise a plurality of plates configured to interface with a plurality of ball connectors, i.e., ball connectors of a handle assembly. The electrical connectors may comprise a ground plate that spans the entire length of the plurality of electrical connectors, i.e., such that a ground connection is the first electrical connection made with corresponding electrical connectors of, e.g., a handle assembly, and the last electrical connection disconnected from corresponding electrical connectors of, e.g., a handle interface. Electrical connectors may be utilized in any convenient manner, and such may vary, including, for example, power connections, ground connections, connections for transmitting and/or receiving data and/or control signals or the like.

Pressure Sensor.

[0104] Embodiments of amplifier assemblies further comprise a pressure sensor configured to sense fluid pressure within the distal waveguide. Pressure sensor may be configured to sense pressure ultimately output by the amplifier assembly, e.g., through a catheter interface of the distal waveguide. Pressure sensors may be configured to sense pressure applied to, for example, a distal balloon operably connected to the amplifier assembly. In some instances, the amplifier assembly includes a pressure sensor operably coupled to the distal chamber. In such instances, the pressure sensor may detect pressure and changes thereof in the liquid in the distal chamber. When included, any convenient type of pressure sensor may be present, where examples of pressure sensors that may be present include, but are not limited to: resistive, capacitive, piezoelectric, optical, and MEMS-based pressure sensors, and the like.

[0105] In embodiments, the pressure sensor is integrated into the distal waveguide. For example, the distal waveguide may be shaped to include a fluidic connection and/or mounting for a pressure sensor in a location that is relatively distal to the distal chamber. In embodiments, the pressure sensor is electrically connected to the electrical assembly, where such connections, e.g., power the pressure sensor or receive output signals from the pressure sensor or control the pressure sensor or the like.

[0106] Some embodiments of the distal waveguide include a pressure sensor receptacle used to house a pressure sensor. The pressure sensor can be fixed via adhesive, heat staking, ultrasonic welding, internal O-Ring seal or O-Ring face seal, set screw with an interference fit, or other sealing method to the distal waveguide.

[0107] In other embodiments, a pressure sensor may be attached to a distal Luer lock operably connected to the distal waveguide via a T-junction on the Luer lock.

Position/Volume Sensor.

[0108] Embodiments of amplifier assemblies further comprise a sensor configured to sense to a position of the diaphragm. By position of the diaphragm, it is meant a position of the diaphragm in a relatively distal or proximal direction with reference to a neutral, centered position of the diaphragm. By position of the diaphragm, it is also meant a position of a central region of the diaphragm. Further, by position of the diaphragm, it is meant a position of the diaphragm indicative of the volume of fluid urged out of the output of the amplifier assembly (e.g., out of the catheter interface of the distal waveguide) and into, for example, a distal balloon or other tissue-engaging element operably connected to the output of the amplifier assembly.

[0109]That is, in some instances, the amplifier assembly includes a positional sensor configured to provide spatial data regarding the position of the diaphragm at a given time, e.g., during use of the amplifier assembly or system of which it forms a part. When present, any convenient positional sensor may be employed. In some instances, the diaphragm positional sensor is a Hall sensor, e.g., which may be employed in conjunction with a magnet (e.g., permanent magnet or electromagnet) or two or more magnets present at one or more fixed locations relative to the diaphragm, such as a fixed location of the amplifier assembly or a handle assembly, etc., such that the fixed magnet is positioned to modulate voltage of the Hall Sensor upon movement of the diaphragm (i.e., translation of the diaphragm in proximal and distal directions).

[0110] For example, the positional sensor may comprise a first magnet integrated into the proximal nose, a second magnet integrated into the distal waveguide at a specified distance from the first magnet, and an electrical probe located in a central region of the diaphragm. In such cases, the electrical probe is configured such that movement of the diaphragm relative to the first and second magnets causes detectable current or voltage changes, e.g., in the probe located in a central region of the diaphragm, indicative of the position of the diaphragm.

[0111] In some cases, the proximal nose comprises a first receptacle configured to hold a first magnet in a fixed position and/or the distal waveguide comprises a second receptacle to hold a second magnet in a fixed position. In embodiments, the first and second magnet receptacles provide locations for a magnet to be fixed in desired locations. Deformation features molded into the proximal nose and distal waveguide can be used to retain the magnets without the need for additional retention mechanisms or processes. Deformation features may comprise, for example, crush ribs or other protrusions designed to hold a magnet in a fixed position. Further, a rear stop limit feature may be used to locate the depth of a magnet with respect to other elements (e.g., a displacement and frequency sensor). That is, embodiments may comprise features, such as specific shapes, to constrain or otherwise precisely locate the position of one or more magnets relative to other elements of the system. In embodiments, the magnetic field of the one or more magnets induces electrical activity or properties, e.g., an electrical current and/or a change in voltage, on a Hall sensor or a probe. Such change or changes in electrical activity or properties are directly related to a distance from the poles of the magnetic fields to the Hall sensor or a probe. Such electrical activity or properties can be calibrated to measure diaphragm displacement directly and a change in volume (e.g., change in volume of fluid displaced; e.g., change in volume of the proximal and/or distal chambers) indirectly. [0112] In some cases, the proximal nose and/or distal waveguide are shaped such that first and second receptacles comprise crush ribs, i.e., protrusions or nibs capable of being compressed thereby holding a magnet under tension within the receptacle. In embodiments, the electrical probe located in a central region of the diaphragm is electrically connected to the electrical assembly, e.g., to power the sensor and/or receive data from the sensor and/or to control the sensor. In other embodiments, the position sensor comprises integrating a magnet into a central region of the diaphragm.

[0113] In other instances, the positional sensor may be an optical sensor, electric field potential sensor, resistive sensor, magnetic sensor, angle sensor, or acceleration sensor. Further, any combination of these sensors may be used to gather positional data of the diaphragm. In cases in which a combination of membrane positional sensors is employed, e.g., to ensure sensors provide correct data across a variety of frequencies, sensor data may be combined through “sensor fusion” techniques, such as those known in the art. When present, a positional sensor may be employed for a variety of different purposes, e.g., to assess vessel compliance and treatment, to assess proper filling of a balloon operably connected to an output of the amplifier assembly, to provide for a way to assess whether the diaphragm has been stretched beyond desired thresholds, etc. Fabrication methods of the positional sensor may include, but are not limited to: adhesives, direct printing, welding, embedding and the like.

[0114] As reviewed above, in connection with including a positional sensor (e.g., a Hall sensor) in an embodiment of an amplifier assembly, the diaphragm may be configured to include a flexible electronics guide and a positional sensor retaining zone where such aspects interact with an electronics assembly. In some embodiments, aspects of the positional sensor (e.g., a Hall sensor or a Hall sensor probe) is attached to the center of the diaphragm, which provides an electronic output (e.g., a voltage output) corresponding to the position of the center of the diaphragm. The position of the center of the diaphragm corresponds to the volume output of the amplifier assembly provided by the sensor.

[0115] Aspects of the positional sensor and/or electronics assembly (e.g., a flexible circuit board) may comprise a thin, rigid plate that is difficult to seal to, which makes it difficult to prevent fluid from escaping from the proximal chamber and/or the distal chamber. To create a seal, and without damaging aspects of the electronics assembly (e.g., a flexible circuit board), while also creating a seal between the proximal nose and the distal waveguide, the diaphragm may comprise a flexible electronics guide zone. Such zone may comprise creating a small slit in the diaphragm (e.g., the circumferential protrusion of the diaphragm; an exterior circumferential O-Ring of the diaphragm) which is sized and configured such that aspects of the positional sensor and/or electrical assembly (e.g., one or more electrical connections to the electronics assembly or a flexible circuit board) can be passed from the central region of the diaphragm to a space outside the proximal or distal chambers (e.g., such that a probe or other aspects of a positional sensor, such as a Hall sensor, is electrically connected to the electronics assembly while still maintaining the diaphragm seal of the proximal and distal chambers). A flexible electronics guide zone of a diaphragm may include a flexible circuit board co-molded with the diaphragm. Such zone may include heat staking to embed such a flexible circuit board within the diaphragm. In embodiments, the flexible electronics guide zone end may comprise creating multiple sealing surfaces within the diaphragm (e.g., between a groove of the proximal nose, as described herein, and a proximal side of a circumferential protrusion (e.g., an O-ring) of the diaphragm, between an inner side of the circumferential protrusion and a flexible circuit board and/or between a distal side of the circumferential protrusion and a groove of the distal waveguide, as described herein).

[0116] In embodiments, to reliably hold a positional sensor, such as a Hall sensor, on or near the diaphragm while the diaphragm translates proximally and distally or during pulsatile intravascular lithotripsy, a feature may be molded into the diaphragm to house aspects of the positional sensor, e.g., a Hall sensor. For instance, a bump or ridge may be molded onto the diaphragm that comprises a pocket such that aspects of the positional sensor (e.g., Hall sensor) can be housed inside. Such a pocket could hold the positional sensor (e.g., Hall sensor) by itself or may also comprise adhesive or very high bond strength tape. Adhesives of interest include cyanoacrylate, UV-cure adhesive or multipart adhesive or the like. In other cases, the positional sensor may be co-molded and embedded within the diaphragm altogether. In some embodiments, it is beneficial that an aspect of the positional sensor and/or electronic connection and/or aspects of the electronics assembly (e.g., flexible circuit board) comprise grooves or ridges configured to hook or grasp the diaphragm thereby creating an interlock. In other cases, aspects of the positional sensor can be heat staked or ultrasonically welded to the diaphragm.

Housing-.

[0117] The disparate components of each of the handle assembly and the amplifier assembly may be present in housings, including in some cases, a single housing. Such housings enclose the various components of the handle assembly and the amplifier assembly to protect the internal components. Such housings may substantially cover the proximal nose, the distal waveguide and the diaphragm as well as other components of the amplifier assembly, as desired. In embodiments, the housings are configured to cover and protect components held therein, i.e., protect internal components from exposure to the environment and/or from wear and tear caused by the introduction of foreign objects. While the form of the housings may vary, in some cases, the housings of the handle assembly and the amplifier assembly comprise one or more snap fit shells configured to substantially enclose the internal components, e.g., the proximal nose, the distal waveguide and the diaphragm. In an embodiment, the housings comprise a shell, a snap fit and an exit port (i.e., a port for attaching an output to the amplifier assembly; i.e., configured to allow space for a catheter or other aspect to be operably connected to, e.g., the catheter interface, to receive pulsatile energy). The housings may be configured to securely connect the amplifier assembly and the handle assembly during use. Any connection system known in the art may be employed that allows the handle assembly and the amplifier assembly to operably connect in a safe and efficient manner during use. In embodiments, the amplifier assembly and handle assembly are easily disconnected by the user releasing the snap fit lock.

[0118] When present, the housings may also cover the electrical assembly; however, the housings may be shaped such that electrical connectors of the electrical assembly are exposed or capable of being exposed in order to form connections with other assemblies or systems, e.g., a handle assembly.

[0119] In embodiments, the housings may also be configured to retain the amplifier system to a handle assembly, e.g., during use. In some cases, the housings comprise one or more flexible arms for interfacing with a handle assembly. Such one or more flexible arms may be configured to hold a proximal interface of the proximal nose in place relative to a handle assembly. In embodiments, the flexible arms are “snap fits” that are bilaterally oriented to provide “quick-connect” retaining features that “snap” into a mating receptacle (e.g., of a handle assembly) when correctly oriented and positioned. These snap fit features may be bowed outward such that during insertion (i.e., into mating receptacles of a handle assembly) they are compressed and then return to their original position when in their mating receptacle. Once the flexible arms (i.e., snap fits) return to their original position, retaining features lock into their respective receptacles (i.e., of a handle assembly) to prevent longitudinal motion (i.e., the amplifier assembly disconnecting from the handle assembly). To release the amplifier assembly, the flexible arms (i.e., the arms of snap fittings) can be compressed inwards to release the retaining features from their respective receptacles. Once the snap fit lock is released, the amplifier assembly can be disconnected from, e.g., a handle assembly.

[0120] In embodiments, the housings may be configured to provide a unit that is configured to be hand-held. In such instances, the hand-held component, e.g., hand-held amplifier assembly, is designed to be held and operated in a single adult human hand. When present in embodiments, the one or more flexible arms may be configured to provide tactile feedback for interfacing with a handle assembly.

[0121] The one or more flexible arms may comprise aspects of a snap fit groove mechanism of an amplifier assembly. In embodiments, the snap fit groove allows the flexible interlocking retaining features on the housing to be compressed during engagement and disengagement with a handle assembly. The depth (i.e., length along a long axis of the amplifier assembly) of the snap fit groove ensures sufficient travel distance for this purpose.

[0122] In some cases, the housings comprise one or more grooved sections or grip points configured for manually gripping the amplifier assembly. In particular, such grooved sections or grip points may be configured to aid in gloved manipulation of the amplifier assembly, as such may be required in an operating environment.

[0123] While the form factor of such housings may vary as desired, in some instances, such housings have a general diameter and/or length ranging from 25 mm to 100 mm, such as 40 mm to 50 mm and length ranging from 50 mm to 150 mm, such as 75 mm to 100 mm.

[0124] Additional details regarding aspects of, or components relevant to, amplifier assemblies that may be incorporated into, or used in conjunction with, embodiments of the present invention are provided in United States Patent No. 1 1 ,464,949; pending PCT Application Serial No. PCT/US2020/055458; United States Application Serial No. 63274832; pending PCT Application Serial No. PCT/US2022/014785; United States Application Serial No. 63238381 ; pending PCT Application Serial No. PCT/US2022/040586; United States Application Serial No. 63346703; pending PCT Application Serial No. PCT/US23/23533; United States Application Serial No. 63346704; pending PCT Application Serial No. PCT/US23/22685; and United States Application Serial No. 63444414; the disclosures of each of which are herein incorporated by reference.

[0125] Various aspects of amplifier assemblies of the invention being generally described above, elements of amplifier assemblies are now further reviewed in the context of specific embodiments.

Specific Embodiments:

[0126] An amplifier assembly in accordance with an embodiment of the invention is depicted in FIG. 1 B. Shown in FIG. 1 B is an isometric view of amplifier assembly 100 with a relatively proximal region of amplifier assembly 100 appearing on the right-hand side of the figure and a relatively distal region of amplifier assembly 100 appearing on the left-hand side of the figure.

[0127] Amplifier assembly 100 comprises proximal nose 110 seen in the relatively proximal region of amplifier assembly 100. Proximal nose 110 comprises proximal interface 120. As described herein, amplifier assemblies of interest interface with a handle assembly 101 (shown in FIG. 1 C) such that proximal interface 120 of proximal nose 110 meets, and operably connects with, a corresponding interface of the handle assembly. High pressure connector 123 is positioned in the center of proximal interface 120 and is configured to receive high-pressure fluid (e.g., pulses of high-pressure fluid) from a pressure source via a handle assembly operably connected to proximal interface 120 of amplifier assembly 100. High pressure connector 123 is configured to provide an interface for high pressure fluid (e.g., pulses of high-pressure fluid), such as high-pressure gas (e.g., compressed air or compressed CO2) to access a proximal chamber internal to amplifier assembly 100 facilitating the translation of the diaphragm present within amplifier assembly causing it to impart pressure in a distal chamber of amplifier assembly 100. High pressure connector 123 seals high pressure fluid within amplifier assembly 100, in part, by an O-ring present in O-ring groove 125 of high-pressure connector 123. In amplifier assembly 100, high-pressure connector 123 is a metal component molded into the plastic of proximal interface 120 of proximal nose 1 10.

[0128] Proximal interface 120 of proximal nose 1 10 can be aligned with a handle assembly 101 , in part, using alignment elements or keying elements 127 such as a keyway present on proximal interface 120. Alignment or keying elements, i.e., keyed face, 127 comprise groves present at locations near a circumference of proximal interface 120 such that corresponding alignment elements present on a handle assembly allow amplifier assembly 100 and a handle assembly to be operably connected in a specific, desired, alignment, e.g., rotational alignment. For example, alignment elements 127 may interface with corresponding elements of a handle assembly 101 such that high-pressure connector 123 properly aligns (i.e., operably aligns or aligns such that a fluidic connection is maintained) with a bore on the handle assembly, or electrical connectors 130 of an electrical assembly properly align (i.e., such that electrical connections are made) with corresponding electrical connectors on a handle assembly and maintains fluidic and electrical connections between the handle assembly 101 and amplifier assembly 100.

[0129] Electrical connectors 130 of an electrical assembly of amplifier assembly 100 are located in an upper and outer region of proximal interface 120 of proximal nose 1 10. Electrical connectors 130 of the electrical assembly comprise flat plates made of electrically conductive material, e.g., a corrosion-resistant metal. Electrical connectors 130 of the electrical assembly comprise flat plates that are located, shaped, positioned and otherwise configured to interface with ball connectors (also referred to as pin connectors) (i.e., substantially round electrical connectors the position of which are biased by springs to physically contact and electrically connect a round end of the ball connector to a plate) of a handle assembly when such a handle assembly is operably connected to amplifier assembly. Pin connectors are well known in the art and comprise substantially round electrical connectors, the position of which are biased by springs to physically contact and electrically connect a round end of the ball connector to a plate. Such plateball (i.e., plate-pin) connection makes electrical connections between components (e.g., plates of electrical connectors 130 and ball connectors of a handle assembly) in a perpendicular orientation relative to the long axis of amplifier assembly 100.

[0130] As described, embodiments of amplifier assemblies are configured to be releasably engaged to an embodiment of a handle assembly according to the invention, such that the amplifier assembly is operably connected to the handle assembly. An amplifier assembly, such as amplifier assembly 100 of FIG. 1 B in accordance with an embodiment of the invention is depicted in FIG. 1 C as well as a handle assembly 101 according to an embodiment of the present invention, illustrating the general orientation of how amplifier 100 assembly may be operably connected to the handle assembly 101 , i.e., such that a proximal interface of amplifier assembly 100 may be brought into contact with a distal interface of handle assembly 101 , such that the two assemblies are releasably engaged to form an operable connection therebetween.

[0131] Electrical connectors 130 of the electrical assembly are arranged in a pattern on an outer region of proximal interface 120 such that, when amplifier assembly 100 is engaged with a handle assembly, corresponding electrical connectors of the handle assembly (e.g., ball connectors) interface with individual plate connectors of electrical connectors 130 of electrical assembly shown in FIG. 1 B. Amplifier assembly 100 has nine individual electrical connectors that are rectangular plates, with an extended, i.e., relatively elongated, plate in the center. The center plate corresponds to a ground connection and is shaped and positioned as such in order that when making electrical connections between electrical assembly 130 of amplifier assembly 100 and a handle assembly, a ground connection is the first electrical connection made and, analogously, when disconnecting such assemblies, the ground connection is the last connection opened. Configuring electrical assembly 130 in such a manner that a ground connection is the first connection made and last connection opened is a safety feature of amplifier assembly 100 and a corresponding handle assembly intended to help ensure that, for example, any unexpected charge in amplifier assembly 100 or an operably connected handle assembly is safely discharged.

[0132] Electrical connectors 130 of electrical assembly may electrically connect outputs from sensors present on amplifier assembly 100. For example, a sensor may be integrated into amplifier assembly 100 that detects the position of the diaphragm within the proximal and distal chambers (e.g., a Hall effect-based sensor, i.e., a Hall sensor) and the output of such sensor may, ultimately, be output to an electrical connector of electrical assembly (i.e., one or more of the plates of the electrical connectors 130 in FIG. 1 B). Similarly, a sensor may be integrated into amplifier assembly 100 that detects pressure within the distal chamber of amplifier assembly 100 and the output of such sensor may, ultimately, be output to another electrical connector of electrical assembly. Other types of sensors may be present in amplifier assembly 100.

[0133] The electrical assembly, to which electrical connectors 130 are electrically connected, further comprises electronic circuitry configured to, for example, receive electrical signals output from sensors or other electrical elements of amplifier assembly 100, modulate such electrical signals as desired and output them to one or more electrical connectors 130. In some cases, the electrical assembly comprises a memory configured as desired, for example, to record sensor readings over time. Such electrical circuitry may be present on, for example, a circuit board, such as a printed circuit board, such as a flexible printed circuit board, positioned within amplifier assembly 100 such that such aspects are not visible when viewing amplifier assembly 100 from the outside. Electrical connectors 130 may also be used to receive signals transmitted from a handle assembly, such as control signals for one or more sensors or power supply for one or more sensors. [0134] In general, electrical connectors 130 may be configured for providing electrical connection to various components of amplifier assembly 100, as desired. For example, electrical connectors of electrical assembly 130 may be used to transmit data regarding diaphragm position, memory, and/or pressure and to provide power to sensors, as desired.

[0135] Distal waveguide 160 is located in amplifier assembly 100 in a relatively distal region thereof. The output of distal waveguide 160 (i.e., such output being transmitted in a relatively distal direction in amplifier assembly 100) is connected to catheter assembly 165 that comprises or is ultimately connected to one or more catheters used for transmitting energy, e.g., pressure, such as pressure pulses or static pressure, output by distal waveguide 160. That is, catheter assembly 165 receives energy, e.g., pressure, such as pressure pulses or static pressure, that, having been received and transmitted by amplifier assembly 100, are ultimately output by distal waveguide 160 of amplifier assembly. Catheter assembly 165 may comprise one or more catheters as well as a housing, e.g., tubing, to enclose such catheters. Catheter assembly 165 may further comprise one or more strain relief aspects, such as flexible tubing or reinforced tubing, e.g., flexible tubing with a metallic spring wound around the exterior or the like, in order to support arranging amplifier assembly 100 as well as related, or interconnected, components, such as a handle assembly (e.g., when an amplifier assembly is operably connected to a handle assembly), a console, and so forth, vis a vis an operating environment, such as an operating room with a patient.

[0136] Housing 190 provides a durable cover for internal elements of amplifier assembly 100, such as, for example, proximal nose 1 10 and distal waveguide 160, such that proximal nose 1 10 and distal waveguide 160 are substantially enclosed within housing 190. Housing 190 is formed by one or more elements, e.g., covers, combined to enclose aspects of amplifier assembly 100, as desired. Housing 190 is configured to protect internal elements of amplifier assembly from wear and tear through use as well as to provide a connector interface used for operably connecting amplifier assembly 100 to a handle assembly. In amplifier assembly 100, such an interface comprises flexible arm 193. Flexible arm 193 includes a ratchet element for insertion into a receptacle of the handle assembly holding amplifier assembly 100 in place relative to handle assembly and maintaining an operable connection of the amplifier assembly and handle assembly during treatment. Such ratchet element of flexible arm 193 snaps into place when operably connecting with the handle assembly, thereby providing tactile feedback, e.g., a “snap” or a “click,” when amplifier assembly 100 (in particular proximal interface 120 of proximal nose 1 10) is operably connected with a handle assembly. Flexible arm 193 and a corresponding receptacle on a handle assembly serve the additional purpose of aligning amplifier assembly 100 and the handle assembly when operably interfacing the two parts, e.g., such that electrical connectors 130 of the electrical assembly align with corresponding connectors of the handle assembly. Flexible arm 193 can be manually manipulated, e.g., manually depressed, to disconnect amplifier assembly 100 from the handle assembly. Flexible arm 193 may be made from a hardened plastic with sufficient strength and firmness to hold amplifier assembly 100 in place when interfacing with a handle assembly. Other mechanisms for reversibly attaching amplifier assembly 100 to a handle assembly are contemplated.

[0137] The exterior of housing 190 is formed to include gripping section 195 with grooves or treads or other shapes or textures to facilitate manually holding and/or manipulating amplifier assembly 100 without it slipping or rotating in an undesired or unexpected manner, even when held by a gloved hand.

[0138] FIG. 2A shows an internal view, i.e., cutaway view, of amplifier assembly 200 according to an embodiment of the invention. Amplifier assembly 200 may be, for example, amplifier assembly 100 seen in FIG. 1 B. In FIG. 2A, elements having the same or similar reference numerals have the same or similar features as corresponding elements in FIGS. 1 A-C, unless explicitly stated otherwise.

[0139] In amplifier assembly 200, diaphragm 270 is held in place within amplifier assembly 200 between proximal nose 210 and distal waveguide 260 with retaining pins 267. In embodiments pins 267 are metal pins, but any materials known in the art are envisioned. Metal pins 267 , i.e., retaining pins, present within amplifier assembly are used to hold diaphragm 270 in place, i.e., by compressing distal waveguide 260 against proximal nose 210. Metal pins 267 may be inserted into holes in, or molded into, e.g., proximal nose 210, such that they contact and abut a distal surface of distal waveguide 260. Other techniques for holding distal waveguide 260 against proximal nose 210 with diaphragm 270 therebetween may also be employed.

[0140] In another embodiment shown in FIG. 2B, diaphragm 270 is held in place within amplifier assembly 200, between proximal nose 210 and distal waveguide 260, with clip 299. FIG. 2B shows amplifier assembly 200 without housing 190. Clip 299 is configured to snap on to proximal nose 210 and distal waveguide 260 to securely hold diaphragm 270 in a sealed position. Clip 299 further comprises tabs 298 on the proximal end of clip 299 to further secure diaphragm 270. Tabs 298 may bend radially inward at hinge 297 or, alternatively, tabs 297 may rotate inwardly. In embodiments, clip 299 is a metal clip, but any materials known in the art, such as, for example, metals and polymers are envisioned.

[0141] Diaphragm 270 is held between proximal nose 210 and distal waveguide 260 such that proximal chamber 212 is sealed off on the relatively proximal side of diaphragm 270 and distal chamber 262 is sealed off on the relatively distal side of diaphragm 270. Diaphragm 270 is configured to translate back and forth (i.e., relatively proximally and relatively distally) within proximal chamber 212 and distal chamber 262. More specifically, diaphragm 270 is configured to translate back and forth (i.e., relatively proximally and relatively distally) between distal face 21 1 (of proximal nose 210) and proximal face 261 (of distal waveguide 260). Diaphragm 270 is configured to do so without producing strain on diaphragm 270. That is, diaphragm 270 is configured to do so without producing tension on diaphragm 270 or without stretching the material of diaphragm 270 or without resistance from the material of diaphragm 270 or without applying stress to the material of diaphragm 270.

[0142] In FIG. 2A, diaphragm 270 is shown in a neutral state, i.e., a relaxed state, i.e., approximately in the middle between distal face 21 1 and proximal face 261 . Such state corresponds to there being relatively equal pressures within proximal chamber 212 and distal chamber 262.

[0143] In amplifier assembly 200, diaphragm 270 comprises pleats 273 that are shaped to allow diaphragm 270 to translate between distal face 211 of proximal nose 210 and proximal face 262 the distal waveguide 260. Depending on the distance diaphragm 270 translates away from the neutral position shown in FIG. 2A, diaphragm 270 is urged to unfold pleats 273 thereby taking on a new shape allowing diaphragm 270 to occupy a new position without producing strain on diaphragm 270. For example, pleats 273 of diaphragm 270 are positioned and shaped such that when diaphragm 270 is translated fully into distal face 21 1 , such pleats unfold and substantially seamlessly contact or envelop distal face 211 . Similarly, pleats 273 of diaphragm 270 are positioned and shaped such that when diaphragm 270 is translated fully into proximal face 261 , such pleats unfold and substantially seamlessly contact or envelop proximal face 261. Diaphragm 270 comprises pleats 273 that are shaped and positioned such that diaphragm 270 can fit within the indentations or curvatures of distal face 211 as well as the indentations or curvatures of proximal face 261 , when translated to fully proximal and distal positions, respectively.

[0144] As described above, proximal nose 210 comprises distal face 21 1 present on an internal distal surface of proximal nose 210. The volume between distal face 21 1 of proximal nose 210 and diaphragm 270 forms proximal chamber 212. In embodiments, proximal chamber 212 receives energy, e.g., pressure such as pressure pulses or static pressure, from, e.g., fluid such as CO2, entering amplifier assembly 200 via high pressure connector 223 of proximal interface 220. Such energy, e.g., pressure such as pressure pulses or static pressure, from, e.g., fluid such as CO2, entering amplifier assembly 200 via high pressure connector 223, is sealed within high pressure connector 223 and proximal chamber 212 by an O-ring present in O-ring groove 225 of high-pressure connector 223. Distal face 211 of proximal nose 210 is shaped so that diaphragm 270, when translated in a fully proximal position, seats itself on distal face 211 of proximal nose 210, i.e., pleats 273 or diaphragm 270 unfold or unfurl to follow the shape of distal face 211 such that diaphragm 270 translates without producing strain on diaphragm 270.

[0145] As described above, distal waveguide 260 comprises proximal face 261 present on an internal proximal surface of distal waveguide 260. The volume between proximal face 261 of distal waveguide 260 and diaphragm 270 forms distal chamber 262. Proximal face 261 of distal waveguide 260 is shaped so that diaphragm 270, when translated in a fully distal position, seats itself on proximal face 261 of distal waveguide 260, i.e., pleats 273 of diaphragm 270 unfold or unfurl to follow the shape of proximal face 261 such that diaphragm 270 translates without producing strain on diaphragm 270.

[0146] Distal chamber 262 receives energy, e.g., pressure such as pressure pulses or static pressure, as diaphragm 270 is translated as a result of energy, e.g., pressure such as pressure pulses or static pressure, applied to proximal chamber 212. Such energy, e.g., pressure such as pressure pulses or static pressure, is transmitted along distal waveguide 260 and ultimately output to catheter assembly 265 fluidically connected to an output of distal waveguide 260 via catheter interface 264, e.g., a threaded connector or a Luer lock mechanism, such as a Luer lock or floating Luer lock, or another operable connector, as desired. Such catheter interface 264 is in fluidic communication with distal chamber 262 of distal waveguide 260. Such catheter interface 264 receives high- pressure fluid, i.e., pulses of high-pressure and/or static pressure, in each case from distal chamber 262. Such pressure may be transmitted via fluid in distal chamber 262, such as, e.g., saline.

[0147] In part, in order to seal proximal chamber 212 and distal chamber 262 (i.e., fluidically seal such chambers), diaphragm 270 comprises substantially T-shaped protrusion 275 at the outer circumference of diaphragm 270. Such protrusion is shaped to seal off a connection between proximal nose 210 and distal waveguide 260 such that fluid does not escape between these elements even when relatively high pressures, including high pressure pulses, are applied to fluid present in either chamber and/or even when diaphragm 270 is translated fully in the proximal or distal directions.

[0148] As described above, proximal nose 210 comprises proximal interface 220 for interfacing with a handle assembly. Proximal interface 220 comprises high pressure connector 223 for receiving energy, e.g., fluid such as fluid pressure pulses or static fluid pressure, where such fluid may be, for example, a gas, such as CO2 or air. Such high- pressure connector 223 is in fluidic communication with proximal chamber 212. That is, high-pressure connector 223 is configured to receive high pressure fluid, i.e., from a handle assembly, and transmit such pressure to proximal chamber 212. High-pressure connector 223 may be made of metal and/or may be molded into the material of proximal nose 210, e.g., molded into plastic of proximal nose 210. High-pressure connector 223 further comprises O-ring groove 225 configured to receive an O-ring. Also as described above, proximal interface 220 comprises alignment elements 227, i.e., keying elements such as a keyway, such as a grove or plurality of groves, configured to align amplifier assembly 200 with a handle assembly.

[0149] Electrical connectors 230 of electrical assembly 235 are shown at a relatively upper position of proximal nose 210. Electrical assembly 235 comprises a flexible printed circuit board electrically connected to electrical connectors 230 as well as outputs of various sensors described herein.

[0150] Distal waveguide 260 is shaped to allow access to a distal region of distal chamber 262 such that pressure sensor 269 can be located on distal waveguide 260 allowing pressure readings of fluid, e.g., saline, present in distal chamber 262. Any convenient pressure sensor 269 capable of measuring fluid and generating electrical signals based on such readings may be employed. Pressure sensor 269 is integrated into distal waveguide 260 in any convenient manner, e.g., via a threaded interface or the like. Pressure sensor 269 is used to sense pressure, including pressure changes, i.e., caused by pressure pulses, within distal chamber 262 and therefore transmitted, or being delivered, through catheter interface 264 and through catheter assembly 265, ultimately to a distal balloon operably connected to amplifier assembly 200. That is, pressure readings obtained by pressure sensor 269 reflect pressure applied by amplifier assembly 200 to, e.g., a distal balloon or other tissue-engaging element, and therefore, as applicable, to a lesion proximal to such balloon or other tissue-engaging element. The output of pressure sensor 269 is electrically connected to electrical assembly 235, such that pressure sensor 269 readings may be processed, stored and/or transmitted (e.g., via electrical connectors 230) by electrical assembly 235.

[0151] Amplifier assembly 200 further comprises one or more sensors for sensing a position of diaphragm 270, i.e., to what extent diaphragm 270 has translated between distal face 21 1 and proximal face 261 . Many commonly available sensors are envisioned. In the embodiment shown in FIG. 2A, amplifier 200 comprises a Hall sensor for such a positional sensor, i.e., to sense a position of diaphragm 270. Such Hall sensor comprises first magnet 276 integrated into proximal nose 210 and second magnet 266 integrated into distal waveguide 260. Such magnets are positioned such that they remain a fixed distance away from each other and in a fixed position of proximal nose 210 and distal waveguide 260, as applicable. Such magnets may be oriented in any convenient orientation with respect to magnetic polarities. The Hall sensor further comprises electrical probe 275 present in a central region of diaphragm 270. Electrical probe 275 is electrically connected to electronics assembly 235 via a “pigtail” connector, i.e., a connector with enough slack built into the length of the connector such that it can follow diaphragm’s 270 movement back and forth towards proximal face 261 and distal face 211 . Such electrical probe may be fastened to diaphragm 270 using any convenient means such as a bonding technique or glue, such as epoxy, or adhesive, so long as electrical probe 270 moves with and to the same extent that diaphragm 270 moves as a result of applying pressure, e.g., pressure pulses or static pressure to amplifier assembly 200.

[0152] The position of diaphragm 270 corresponds to a volume of (or changes in volume of) distal chamber 262, which in turn correspond to volume changes of a balloon or other tissue-engaging element operably connected, via catheter interface 264 and catheter assembly 265, to amplifier assembly 200. Such volume changes of a balloon or other tissue-engaging element provide, for example, information relevant to treatment of a lesion, e.g., potentially indicating changes in balloon volume when the same or different pressures are applied to the balloon, i.e., information relevant to vessel compliance. Proximal nose 210 comprises a first receptacle to hold the first magnet in a fixed position. Distal waveguide 260 comprises a second receptacle to hold the second magnet in a fixed position. Such receptacles may comprise any convenient technique or mechanism for holding magnets in fixed positions, such as bonding, adhesives, glue, mechanical configurations or the like. For example, first and second receptacles comprise crush ribs, meaning protrusions (i.e., ribs) around an outer circumference of a receptacle between which a magnet is positioned, thereby compressing (i.e., crushing) such ribs such that the magnet is held in tension between such ribs.

[0153] In embodiments, a positional sensor may be configured such that a magnet may be present on a central region of diaphragm 270 and one or more electrical probes may be located on a fixed position of distal waveguide 260 and/or proximal nose 210. Such configuration may represent easier manufacturing aspects or longer useful life of amplifier assembly 200 insofar as the magnet present on diaphragm 270 does not require an electrical connection to electronics assembly 235.

[0154] Housing 290 is present around the exterior of proximal nose 210, distal waveguide 260 and diaphragm 270, such that such elements are substantially enclosed by housing 290. Hosing 290 is shaped to expose proximal interface 220 for interfacing with a handle assembly and to expose the output of catheter interface 264, such that output of amplifier assembly 200 is transmitted to catheter assembly 265.

[0155] FIGS. 3A-B depict a proximal nose of an amplifier assembly according to an embodiment of the invention. In FIGS. 3A-B, elements having the same or similar reference numerals have the same or similar features as corresponding elements in FIGS. 1 -2, unless explicitly stated otherwise.

[0156] FIG. 3A depicts an exterior view of proximal nose 310 of an amplifier assembly, such as amplifier assembly 100 shown in FIG. 1 B or amplifier assembly 200 shown in FIG. 2A. The proximal-most side of proximal nose 310 is shown on the right-hand side of the figure and this side of proximal nose comprises a chamfered edge circumference. This side of proximal nose 310 is chamfered to ease alignment and forming an operable connection with a handle assembly. Holes 368 are included for inserting pins, such as metal, e.g., steel, pins, i.e. , retaining pins, such as pins 267 shown in FIG. 2A, for holding proximal nose 310 together with distal waveguide 260 (e.g., holding proximal nose 210 against distal waveguide 260 and sealing diaphragm 270 between proximal nose 210 and distal waveguide 26; e.g., compressing diaphragm 270 between proximal nose 210 and distal waveguide 2600).

[0157] The proximal side or a proximal region (shown on the right-hand side of the figure) of proximal nose 310 is configured to substantially cover or enclose proximal interface 320 including high-pressure connector 323 (i.e., high-pressure connector 323 does not protrude or extend proximally beyond proximal nose 310) such that these elements are partly protected from inadvertent damage or wear and tear.

[0158] FIG. 3B depicts a cross sectional, i.e., cutaway, view of proximal nose 310. Distal face 31 1 of proximal nose 310 defines proximal chamber 312 (which is sealed when a diaphragm is present). The shape, i.e., the curvature, of distal face 31 1 is selected to correspond to pleats or folds of a diaphragm, such that a diaphragm interfaces with distal face 31 1 in the diaphragm’s proximal-most position. Proximal interface 320 comprises high-pressure connector 323, fluidically connected to proximal chamber 312, with O-ring groove 325 for seating an O-ring that seals the interior of high-pressure connector 323 when a handle assembly is operably connected to proximal nose 310 at proximal interface 320. High-pressure connector 323 is fluidically connected to proximal chamber 312 such that energy, e.g., pressure pulses or static pressure, such as pneumatic pressure pulses or static pneumatic pressure, received via high-pressure connector 323 are transmitted to proximal chamber 312 as well as a diaphragm present at a distal region of proximal chamber 312 and sealing proximal chamber 312. High-pressure connector 323 is made from a metal integrated into the material (e.g., plastic) of proximal nose 310.

[0159] Proximal nose 310 comprises first magnet compartment or receptacle 378 for receiving a first magnet (not shown) that comprises a part of a position sensor, e.g., a Hall sensor, for sensing a diaphragm position as it translates between distal face 311 of proximal chamber 312 and a proximal face of a distal chamber. First magnet compartment or receptacle 378 comprises crush ribs 377 (i.e., pieces of first magnet compartment 378 extending out from the surface thereof) for holding a magnet in a fixed position within first magnet compartment or receptacle 378 by squeezing or crushing a magnet therebetween.

[0160] FIGS. 4A-B depict a distal waveguide of an amplifier assembly according to an embodiment of the invention. In FIGS. 4A-B, elements having the same or similar reference numerals have the same or similar features as corresponding elements in FIGS. 1 -3, unless explicitly stated otherwise.

[0161] FIG. 4A depicts an exterior view of distal waveguide 260 of an amplifier assembly, such as amplifier assembly 100 shown in FIG. 1 B or amplifier assembly 200 shown in FIG. 2A. Distal waveguide 460 is oriented such that the proximal side is depicted on the right-hand side of the figure and the distal side is depicted on the left-hand side of the figure. The proximal side of distal waveguide 460 is shaped to interface with a diaphragm. [0162] The outer circumference of the proximal side comprises rounded chamfer or shelf 463 configured to interface with a protrusion on the outer circumference of a diaphragm (such as, e.g., element 275 of diaphragm 270 shown in FIG. 2A) such that a diaphragm can be sealed between a proximal nose and distal waveguide 460, thereby sealing distal chamber 462.

[0163] Distal waveguide 460 is shaped to include a pressure sensor interface 471 that receives a pressure sensor (such as, e.g., pressure sensor 269 of FIG. 2A). Such interface 471 allows a pressure sensor to be integrated into distal waveguide 460 in any convenient manner, e.g., via a threaded interface or the like. Pressure sensor interface 471 is fluidically connected to an output of distal chamber 462 such that a pressure sensor positioned in interface 471 can sense pressure, including pressure changes, i.e., caused by pressure pulses, within distal chamber 462. Such pressure readings therefore correspond to pressure transmitted through catheter interface 464, ultimately to a distal balloon operably connected to distal waveguide 460. Pressure sensor interface 471 is located such that a pressure sensor present in such interface can be electrically connected to an electrical assembly of an amplifier assembly.

[0164] Catheter interface 464 comprises any convenient mechanism for attaching a catheter to receive output energy, e.g., pressure pulses or static pressure, e.g., of fluid such as saline fluid, transmitted from distal chamber 462 to catheter interface 464. Such mechanisms may comprise, for example, a Luer lock or a floating Luer lock or the like. In FIG. 4A, catheter interface 464 is shown comprising threading for a threaded interface to an output catheter assembly.

[0165] The exterior shape of distal waveguide 460 comprises rounded surfaces 472 shaped to receive pins, i.e., retaining pins, such as steel pins (such as pins 267 shown in FIG. 2A), that span a width of a proximal nose (such as proximal nose 210 shown in FIG. 2A) through holes therein (such as holes 368 shown in FIGS. 3A-B) thereby holding distal waveguide 460 again a proximal nose and sealing a diaphragm therebetween.

[0166] FIG. 4B depicts a cross sectional, cutaway, view of distal waveguide 460. Proximal face 461 of distal waveguide 460, together with a diaphragm define distal chamber 462. Proximal face 461 is shaped such that folds or pleats of a diaphragm can unfold to meet the surface of proximal face 461 (i.e., in the distal-most position of such diaphragm) without producing strain on such diaphragm.

[0167] Second magnet compartment or receptacle 478 is located in a distal region of distal chamber 461 and is shaped to receive a magnet (not shown) that comprises a part of a position sensor, e.g., a Hall sensor, for sensing a diaphragm position as it translates between proximal face 461 of distal chamber 462 and a distal face of a proximal chamber. Second magnet compartment or receptacle 478 comprises crush ribs 477 (i.e., protrusions from second magnet compartment 478 extending out from the surface thereof) for holding a magnet in a fixed position within second magnet compartment 478 by squeezing or crushing a magnet therebetween.

[0168] FIGS. 5A-C depict schematics of a diaphragm of an amplifier assembly according to an embodiment of the invention. In FIGS. 5A-C, elements having the same or similar reference numerals have the same or similar features as corresponding elements in FIGS. 1 -4, unless explicitly stated otherwise.

[0169] FIG. 5A depicts diaphragm 570 showing a distal surface of diaphragm 570. By distal surface, it is meant a side of diaphragm 570 that is oriented towards a distal region of an amplifier assembly when diaphragm 570 is installed therein. Such distal surface is oriented towards and can make contact with a proximal face of a distal chamber (e.g., proximal face 461 of distal chamber 462 shown in FIG. 4B). FIG. 5B depicts diaphragm 570 showing a cutaway view of diaphragm 570. FIG. 5C depicts diaphragm 570 showing a proximal surface of diaphragm 570. By proximal surface, it is meant a side of diaphragm 570 that is oriented towards a proximal region of an amplifier assembly when diaphragm 570 is installed therein. Such proximal surface is oriented towards and can make contact with a distal face of a proximal nose (e.g., distal face 311 of proximal chamber 462 shown in FIG. 3B).

[0170] Diaphragm 570 comprises folds 573. Folds 573 are shaped so that diaphragm 570, when installed in an amplifier assembly between a proximal nose and a distal waveguide, can translate between a distal face of the proximal nose and a proximal face of the distal waveguide by unfolding folds 573 thereby not producing strain, or not producing substantial strain, on diaphragm 570, i.e., without producing strain on diaphragm material or without producing tension on the diaphragm or without stretching diaphragm material or without resistance from diaphragm material or without applying stress to diaphragm material. That is, diaphragm 570 unfolds itself, taking on new shapes, ultimately conforming to a distal face of a proximal nose in the proximal-most position, and conforming to a proximal face of a distal waveguide in the distal-most position. Diaphragm 570 comprises circumferential protrusion 575 at a region of an outer circumference of diaphragm 570. Protrusion 575 is present on diaphragm 570 in order to enable diaphragm 570 to maintain its seal vis-a-vis a proximal chamber and a distal chamber, even while translating between a distal face of a proximal nose and a proximal face of a distal waveguide. Protrusion 575 is shaped to interface with, for example, shelf or chamfer 463 of a distal waveguide shown in FIGS. 4A-B.

[0171] FIGS. 6A-C depict schematics of a housing of an amplifier assembly according to an embodiment of the invention. In FIGS. 6A-C, elements having the same or similar reference numerals have the same or similar features as corresponding elements in FIGS. 1 -5, unless explicitly stated otherwise.

[0172] FIG. 6A depicts housing 690 from a bottom view, looking up at housing 690 with a relatively proximal side of housing 690 at the top of the figure and a relatively distal side of housing 690 at the bottom of the figure. FIG. 6B depicts a cutaway view of housing 690, showing the shape of internal cavity 691 of housing 690. Internal cavity 691 is shaped such that housing 690 can substantially cover a distal waveguide, a diaphragm and a proximal nose as well as other components, such as an electrical assembly. FIG. 6C depicts an isometric view of housing 690.

[0173] Housing 690 provides a durable cover for internal elements of an amplifier assembly present therein. Housing 690 is shaped to include flexible arms 693 for operably connecting an amplifier assembly enclosed within housing 690 to a handle assembly. The exterior of housing 690 is formed to include gripping sections 695 with grooves or treads or other shapes or textures to facilitate manually holding and/or manipulating an amplifier assembly present within housing 690 without it slipping or rotating in an undesired or unexpected manner.

[0174] One embodiment of an amplifier assembly may be assembled by following steps 1 through 12 depicted in FIG. 7A, which assembly instructions illustrate interconnections between elements of such embodiment. Another amplifier assembly may be assembled by following steps 1 through 13 depicted in FIG. 7B, which assembly instructions illustrate interconnections between elements of such embodiment.

HANDLE ASSEMBLIES

[0175] As reviewed above, handle assemblies for controllably transmitting energy are provided. In embodiments, handle assemblies control the transmission of first pulse energy to be delivered to the amplifier assembly. As shown in FIGS. 8A-8F, aspects of a handle assembly 800 comprises: a coupler assembly 850 operably connected to an energy source; a manifold 830, operably connected to the energy source through the coupler assembly 850 and configured to controllably transmit energy to a distal interface 810; and the distal interface 810, operably connected to an output of the manifold 830 and configured to transmit energy received from the manifold 830. In embodiments, handle assemblies are configured to be operably connected to amplifier assemblies, such as those described herein, and to transmit energy from an energy source to the amplifier assembly.

[0176] Embodiments of handle assemblies are configured to operably interface with an amplifier assembly, e.g., embodiments of amplifier assemblies described herein. In embodiments, handle assemblies 800 are configured to be releasably engaged to an amplifier assembly 200 such that the two assemblies form an operable connection. When engaged and in operation, the handle assembly delivers a first energy to the amplifier assembly. Such operable connection may, for example, be configured to facilitate the transmission of energy from the handle assembly to the amplifier assembly. Such operable connection may also, for example, be configured to facilitate certain electrical connections between the handle assembly 800 and the amplifier assembly 200, such as electrically connecting power connections, data connections, control connections or common ground connections. In embodiments, the handle assembly 800 may comprise alignment features, such as keying elements 815 or a specific shape, such as an asymmetrical shape, that allows handle and amplifier assemblies to be releasably engaged with each other in only a single specified orientation, i.e., an orientation that aligns, e.g., a high-pressure connector 223 of the amplifier assembly 200 with a bore 820 of the handle assembly 800, such that energy may be safely transmitted form the handle assembly 800 to the amplifier assembly 200. In certain cases, such alignment features further ensure the interconnection of certain electrical connectors on the handle assembly with certain electrical connectors on the amplifier, as described herein.

[0177] In embodiments, the handle assembly comprises a distal interface configured to operably interface with a proximal nose of an amplifier assembly. In some cases, an alignment feature of the distal interface is configured to interface with a corresponding alignment feature of a proximal nose of an amplifier assembly. For example, the alignment feature of the distal interface may comprise a keyed face and the proximal nose of the amplifier assembly comprises a corresponding keyed face.

[0178] Handle assemblies may be configured to be reusable or single use, as desired. In cases where the handle assembly (or aspects thereof) is reusable and could contact a patient area, such assembly can be configured to be covered in a disposable, sterile sleeve or bag such that the handle assembly may be used while not contaminating a sterile field of an operating room.

Distal Interface-.

[0179] Embodiments of the handle assembly are configured to operably connect with an amplifier assembly, such as amplifier assemblies described herein. Embodiments of the handle assembly and the amplifier assembly are configured such that the two assemblies can be aligned and connected manually, i.e., by hand or by gloved hand (as such may be required in an operating environment). In embodiments, the distal interface of the handle assembly comprises one or more alignment features configured to enable such alignment and operable connection with an amplifier assembly. In some cases, the alignment features comprise a keyed protrusion configured to align the handle assembly with an external component, such as an amplifier assembly, such as a keyed face or keyway of an amplifier assembly.

[0180] Embodiments of the distal interface are configured to operably interface with the proximal nose of an amplifier assembly. When present, an alignment feature of the distal interface may be configured to interface with a corresponding alignment feature of the proximal nose of an amplifier assembly. In embodiments, alignment features of the handle assembly, and corresponding alignment features of an amplifier assembly, may be used to align electrical connectors of an electrical assembly of the handle assembly with electrical connectors of an electrical assembly of the amplifier assembly.

[0181] In an embodiment, the distal interface of the handle assembly (which may be referred to as a receptacle of the handle assembly) retains and secures the amplifier assembly during use and prevents incorrect usage of the assemblies. The distal interface may be configured to mate with a proximal interface of the proximal nose of an amplifier assembly using, as described herein, a keyway that controls the rotational, axial, and radial position of the amplifier assembly relative to the distal interface of the handle assembly. In some cases, the distal interface of the handle assembly comprises a substantially round keyway shape with a grooved detent. However, other configurations to control position and orientation of the handle assembly relative to the amplifier assembly can be employed. [0182] In some embodiments, a key present on the distal interface of the handle assembly is configured to slide into a corresponding keyway in the proximal interface of an amplifier assembly. In some cases, the distal interface of the handle assembly is machined from a metal, such as steel, stainless steel, aluminum, brass or other metal, as desired. When present, a key on the distal interface may be substantially straight with uniform (nondrafted) walls or sides. Embodiments of a corresponding proximal interface of an amplifier assembly may be injection molded, which process may be configured to yield walls with a draft angle. Such drafts may be utilized to guide a key of the distal interface of the handle assembly into a locating keyway of the proximal interface of the amplifier assembly that ensures alignment of the amplifier assembly as it is inserted into the distal interface of the handle assembly.

[0183] In other embodiments, however, a different keying mechanism may be utilized on the handle assembly and corresponding amplifier assembly, such as having an additional keyway on the distal interface of the handle assembly and a key on the proximal interface of the amplifier assembly. In yet other embodiments, the distal interface may have alignment features within the keyway that receive the corresponding features on a key of the amplifier assembly.

[0184] In embodiments, the distal interface of the handle assembly may be configured to facilitate interfacing with an amplifier assembly. In an embodiment, openings (e.g., two, three, four, five or more openings) on a feature of the distal interface may be configured to receive mating and locking arms or snaps or other elements of a keyed interface, as convenient, of an amplifier assembly. Such openings may be through-wall or blind holes with a circular or oblong shape. Such openings may have grooves that compress snaps or snap fits or flexible arms of the amplifier assembly during insertion of the amplifier assembly into the receptacles. Edges of such openings may retain the snaps or snap fits or flexible arms while operating the handle assembly and the amplifier assembly, e.g., during pulsatile energy transmission. In some embodiments, retaining the handle assembly’s orientation and operable connection to an amplifier assembly may comprise one or more of a screw, mechanical, magnetic, or electromechanical latch, push-to- connect, or the like, which elements may be present on the distal interface of the handle assembly. [0185] As reviewed above, in embodiments, the distal interface of the handle assembly is configured to transmit energy received from the manifold. In embodiments, the distal interface is configured to transmit such energy from the handle assembly to an amplifier assembly operably connected thereto. In some embodiments, the handle assembly comprises an outlet port to transmit energy (e.g., high-pressure gas) out of the handle assembly to an amplifier assembly. In some cases, the distal interface of the handle assembly comprises a bore configured to interface with the amplifier assembly, for example, to receive and interface with a high-pressure connector (i.e., a connector nose of a high-pressure connector) of the amplifier assembly. Such bore may comprise an outlet port of the manifold (e.g., an output port of an oscillator, e.g., solenoid valve, of the manifold) and may be sized appropriately to create a seal with, for example, the connector nose of the high-pressure connector, e.g., an O-ring present on a connector nose of the high-pressure connector. In embodiments, in part to prevent misalignment between such bore of the distal interface of the handle assembly and a connector nose of a high- pressure connector of the proximal interface of an amplifier assembly, which could result in, for example, O-ring eccentricity and/or a high-pressure fluid leak (e.g., gas leak) during treatment, the distal interface and alignment features thereof (e.g., alignment key) are used to align the amplifier assembly so that desired alignment is attained at the time when the connector nose of the high-pressure connector enters the bore. In other embodiments, the bore is configured only to create a seal with the connector nose of the high-pressure connector of the amplifier assembly and not to locate the proximal connector within the receptacle.

Coupler Assembly.

[0186] As reviewed above, handle assemblies of the present invention comprise a coupler assembly operably connected to an energy source. That is, coupler assemblies are configured to receive energy from an energy source and convey such energy within the handle assembly to the manifold. In embodiments, the coupler assembly is operably connected to the manifold of the handle assembly. For example, the manifold may be operably connected to the energy source through an input coupler of the coupler assembly. In some embodiments, the coupler assembly comprises input and exhaust couplers, wherein the input coupler is operably connected to an energy source and the exhaust coupler is configured to exhaust energy from the energy source. In an embodiment, the coupler assembly comprises tubing, such as, for example, input and exhaust tubing. When present, the input tubing may be operably connected to an energy source and the exhaust tubing may be configured to exhaust energy from the energy source.

[0187] In embodiments, the handle assembly comprises a coupler assembly comprising an inlet port. In some cases, the coupler assembly (or inlet port thereof) may receive energy (e.g., high-pressure gas) from an energy source through a tube or hose in some cases with high-pressure fittings, as such are known in the art. The coupler assembly (or inlet port thereof) may be connected to one or more of a pressure sensor and a solenoid. In order to simplify a machining process involved in manufacturing embodiments of handle assemblies and reduce the need for, for example, plug fittings, a hole between a pressure sensor, when present, the coupler assembly (or inlet port thereof) and an oscillator of the manifold (e.g., a solenoid) can be created through a single bore (in an area referred to as a pressure sensor port zone). Such inlet port may comprise a filter, such as a particle filter, to minimize the likelihood that particles enter the manifold or the oscillator thereof or a fluid pathway (i.e., a gas pathway).

[0188] In some instances, the handle assembly is configured such that the coupler assembly (or an inlet port thereof) is directly aligned (e.g., substantially linearly aligned) with an outlet port of the handle assembly (e.g., the distal interface of the handle assembly and/or, when present, a bore of the handle assembly) so as to minimize the number of sharp turns the high-pressure gas must take, which reduces the energy stored in the fluid (e.g., gas).

[0189] In an embodiment, the coupler assembly comprises a relatively long, flexible tube configured to interface with an energy source such that it can carry high pressure fluid (e.g., high pressure gas) to the handle assembly and/or carry exhaust out of the handle assembly and/or carry electrical signals and/or communications to and from the handle assembly and/or power to the handle assembly, for example. The coupler assembly may be configured to have a protective seal, e.g., around the outside of aspects of the coupler assembly, to protect it from external wear and tear in an operating environment. Manifold'.

[0190] Handle assemblies of the present invention further comprise a manifold. In embodiments, the manifold is operably connected to an energy source through the coupler assembly and configured to controllably transmit energy to the distal interface of the handle assembly. In embodiments, the manifold is configured to receive high pressure fluid, e.g., high pressure gas, and controllably transmit such high-pressure fluid to the distal interface of the handle assembly.

[0191] In some embodiments, the manifold comprises an oscillator operably connected to the energy source. When present, the oscillator may be configured to transmit energy through the manifold in a first position and to exhaust energy in a second position. That is, the oscillator may be configured to transmit pulses of energy to the distal interface of the handle assembly.

[0192] In certain instances, the manifold may receive energy such as from one or more energy sources (e.g., of one or more console units comprising one or more energy sources) and distribute that energy to one or more oscillators in the manifold. In some cases, there is a one-to-one correspondence between energy sources and oscillators in the manifold. In other cases, a single energy source may deliver energy to one or more oscillators. In still other cases, one or more energy sources may deliver energy to a single oscillator, e.g., for example, such that the energies of the one or more energy sources are combined in a single oscillator.

[0193] In embodiments, energy transmitted to the oscillator comprises a regulated or unregulated fluid under pressure. The oscillator may be actuated to output a pulsatile and/or a static pressure output. In certain embodiments where the energy transmitted by the energy source is a regulated or unregulated fluid under pressure, the oscillator may comprise a solenoid valve. Such solenoid valve may comprise, for example, a two- position, three-way, normally closed solenoid valve. In such instances, the solenoid valve is configured to receive the high-pressure regulated or unregulated fluid. Such a solenoid valve may be configured to have two modes, an “on” mode and an “off” mode. Such a solenoid valve may be configured to have three ports: a port operably connected to the high-pressure regulated or unregulated fluid (i.e., an input port), a port operably connected to, ultimately, an amplifier assembly (i.e., via a distal interface), and an exhaust port (i.e., a second output port). The solenoid valve may be configured such that when turned on (i.e., in an “on” mode), the valve allows the high-pressure regulated or unregulated fluid to be transmitted, i.e., transmitted downstream in the handle assembly, such as transmitted to an amplifier assembly operably connected to the handle assembly. The valve may be further configured such that when turned off (i.e., in an “off” mode), the solenoid changes, i.e., reverses, the connected ports such that the distal side of the valve is exhausted (e.g., exhausted to atmosphere or vacuum). That is, in the “off” mode, the first output port may be connected to the second output port, thereby exhausting high pressure fluid present on the distal side of the solenoid valve.

[0194] In certain embodiments, a frequency and/or duty cycle of the oscillator may be adjusted to generate a desired output, e.g., an appropriate output for treatment, and for the amplifier assembly, including, e.g., a tissue-engaging element, e.g., a distal balloon, operably connected thereto. In various embodiments, the one or more oscillators of the manifold may be configured to oscillate at one or more frequencies and/or duty cycles. In certain instances, an oscillator configured to deliver, for example, pulsatile intravascular lithotripsy to cardiovascular tissue may be configured to oscillate at a frequency between 0 and 50 Hz, such as 1 -10 Hz or 10-20 Hz or 21 -30 Hz or 31 -40 Hz or 41 -50 Hz, and a duty cycle between 10% and 90%, such as 10% or 20% or 30% or 40% or 50% or 60% or 70% or 80% or 90%. In instances in which an oscillator is configured to use fluid pressure to deliver pulsatile pressure pulses for a treatment involving enabling vessel perfusion of cardiovascular tissue, the oscillator may be oscillated at a frequency between 0.25 Hz and 5 Hz, such as 1 Hz or 2 Hz or 3 Hz or 4 Hz or 5 Hz, and a duty cycle between 10 and 90%, such as 10% or 20% or 30% or 40% or 50% or 60% or 70% or 80% or 90%. In instances in which an oscillator is configured to deliver pulse energy comprising an optical or high voltage source, the oscillator may be oscillated at a frequency of 0.1 Hz to 1 GHz such as 1 Hz or 2 Hz or 3 Hz or 4 Hz or 5 Hz or more and a duty cycle between 0.0001 % and 90% such as 0.001% or 0.01% or 0.1 % or 1% or 10% or 20% or 30% or 40% or 50% or 60% or 70% or 80% or 90%.

[0195] In certain embodiments, output from the oscillator of the manifold, or, in embodiments with more than one oscillator, outputs from the various oscillators, can be transmitted to one or more locations. In other embodiments that comprise more than one oscillator, the oscillators can be synchronized with each other, e.g., such that pulsatile energy transmitted from each oscillator is synchronized as desired, e.g., in terms of magnitude, frequency, phase, duty cycle, etc. In other embodiments, the oscillator can be synchronized with external factors or systems or sensors such as, for example, the results of an electrocardiogram (ECG), or can be adjusted based on feedback from other aspects of the handle assembly, an amplifier assembly or other aspects of a system of which such assemblies form a part (e.g., such as volume or pressure measurements, such as volume or pressure measurements detected by sensors present on a tissueengaging element, e.g., a distal balloon, operably connected to an amplifier assembly).

[0196] As reviewed above, when present, the oscillator may be a solenoid, and such solenoid valve may be attached to other aspects of the handle assembly in any convenient configuration. In some cases, the solenoid (sometimes referred to as a solenoid valve) may be a normally shut-off solenoid (i.e., a solenoid configured to vent the outlet port to exhaust when in an “off” position and pressurize the outlet port, e.g., a bore of the distal interface, when in an “on” or “open” position). In some cases, the solenoid is configured to employ linear motion of a plunger in connection with transitioning between “on” and “off” positions. In some cases, such linear motion is achieved by the action of a spring and an electromagnetic coil. In other embodiments, side-to-side or rotary action of a plunger generates the opening and closing of the solenoid (i.e., the opening and closing of a solenoid valve).

[0197] In embodiments, aspects of the handle assembly, including, for example, the manifold can be shaped to fit and be fixed within a surrounding enclosure, i.e., a housing, as described below. Embodiments of aspects of the handle assembly, including, for example, the manifold, can be machined from solid metal (e.g., stainless steel, aluminum, brass or other metals, as desired) blocks or cast using processes such as lost wax casting with a material such as brass (or other materials, as desired) or can be injection molded from thermoplastic materials such as Nylon-12, PEEK, or ABS that can be glass or fiber- filled. Electrical assembly.

[0198] Embodiments of handle assemblies further comprise an electrical assembly (also referred to as an electronics assembly). The electrical assembly may be operably connected to any other aspects of the handle assembly, e.g., the manifold, and/or configured to be operably connected to external devices. Electrical assemblies may be configured to perform various functions, as desired, including, for example, powering various sensors throughout or external to the handle assembly, controlling such sensors, receiving data from such sensors, recording and/or transmitting, e.g., wirelessly transmitting, such data to another location, controlling various aspects of the handle assembly or aspects external to the handle assembly and/or storing information about the handle assembly or an amplifier assembly to which it is connected or other aspects of the system to which the handle assembly is connected, for example.

[0199] In some cases, the electrical assembly comprises a controller programmed to perform self-check routines confirming the safety of the amplifier assembly and/or selfdiagnostic routines, for example. In an embodiment, the electrical assembly is a flexible printed circuit board and is configured to perform several functions including, for example, creating an electrical connection to an amplifier assembly and/or storing catheter, balloon and/or other treatment specific information in a memory or reading such information therefrom.

[0200] In embodiments, the electrical assembly is configured to control the oscillator. When so configured, the electrical assembly may be configured to move the oscillator from a first position to a second position, e.g., from an “off” position to an “on” position. In some cases, the electrical assembly is configured to interface with an external component, such as, for example, an amplifier assembly or one or more energy sources or a user console or other external components, as desired. In some cases, the electrical assembly is electrically connected to a plurality of pin connectors; e.g., the handle assembly may comprise pin connectors configured to interface with plate connectors of an amplifier assembly.

[0201] In certain embodiments, the handle assembly comprises an electronics bay configured to house an electronics assembly (or aspects thereof, e.g., a printed circuit board). Such electronics bay may be configured so that electrical contacts (e.g., pins configured for electrical contact, sliding contacts, rolling contacts, flexible contacts or the like, which elements may be present on a printed circuit board) are positioned at a location and/or orientation and/or level relative to the external component to which such contacts make a connection, e.g., an amplifier assembly. In embodiments, a seal can be created between aspects of the electronics assembly (e.g., a printed circuit board) and the electronics bay. Such seal may be configured to limit, either partially or completely, the amount fluid that can enter into the handle assembly.

[0202] In an embodiment, the electrical assembly comprises a plurality of electrical connectors, comparators, logic gates and power management zones and such may be present at least in part on, for example, a printed circuit board. When present on a printed circuit board, connectors of the printed circuit board may be oriented within the handle assembly such that the connectors are positioned in a desired location of the handle assembly or the electronics bay thereof, e.g., to make an operable connection with an amplifier assembly. In some cases, the electronics assembly or printed circuit board thereof comprises one or more protective features configured to protect the connectors that interface with external components, e.g., an amplifier assembly that slides into and out of the distal interface of the handle assembly (or other receptacle of the handle assembly, as applicable). In embodiments, the electrical assembly can be configured to perform several specific functions, including, for example, (1 ) detection of and/or disconnection from an amplifier assembly; (2) power or energy delivery to LEDs, an oscillator, such as a solenoid and/or an amplifier assembly; (3) comparison of sensor readings, such as, for example, comparison of handle pressure sensor readings against a maximum pressure allocated for the amplifier assembly; (4) detection of a positional sensor (e.g., Hall sensor) limit switch (i.e., as such may be present on an amplifier assembly) detection; and/or (5) safety limit detection and power shut-off.

[0203] As described herein, embodiments of the handle assembly comprise a plurality of electrical connectors. Such connectors may be configured to interface with a handle assembly, as described herein, and configured to communicate any desired data or control signals or used to transmit power or to connect a common ground, in each case between such assemblies. In some cases, the plurality of connectors present on the handle assembly are pin connectors (also referred to as ball connectors). By pin connectors, it is meant that a cylinder made of electrically conductive material, such as any convenient metal, operably connected to a spring that urges the cylinder longitudinally toward a complementary connector on, for example, an amplifier assembly. The spring or other biasing element is configured to ensure the electrical connectors maintain a consistent physical, and therefore electrical, connection. In embodiments, the complementary connectors of the amplifier assembly comprise plate connectors, i.e., planar surfaces comprising electrically conductive materials, such as any convenient metal. In embodiments, an end of a pin connector of the handle assembly is urged to physically, and therefore electrically connect with a corresponding plate connector of the amplifier assembly. Embodiments of the handle and amplifier assemblies comprise any number of electrical connectors, e.g., any number of pin connectors or plate connectors, as applicable, such as one or more, such as five or more, such as ten or more, such as twenty or more, such as 2, 5, 10, 12, 16, 32 or 64 or more pins.

[0204] When present, pin connectors of a handle assembly may be arranged substantially in a V-shaped pattern. In such embodiments, the apex or vertex of the V-shaped pattern may be electrically connected to ground. When such arrangement is used to operably connect to an amplifier assembly comprising plate connectors, the plate connectors may be arranged to receive the V-shaped pattern of pin connectors and configured accordingly. In such cases, the plurality of pins and the plurality of plates may be arranged such that an electrical connection to ground is the initial electrical connection made upon operably connecting the amplifier assembly to the handle assembly. For example, when pin connectors are connected in a V-shaped pattern with a ground connection at the apex or vertex of the V-shape, the first electrical connection made when the handle assembly is operably connected to an amplifier assembly is a ground connection. This is because the connector at the apex or vertex of the V-shaped arrangement is located such that it is the closest to the amplifier assembly when operably connecting the two assemblies (i.e., such pin is at a distal-most position of the plurality of pins). In such cases, the plurality of pins and the plurality of plates are arranged such that an electrical connection to ground is made prior to making other electrical connections upon operably connecting the amplifier assembly to the handle assembly. Similarly, in embodiments, the plurality of pins and the plurality of plates are arranged such that an electrical connection to ground is the last electrical connection to be disconnected when disconnecting the amplifier assembly from the handle assembly. That is, in embodiments, the plurality of pins and the plurality of plates are arranged such that an electrical connection to ground is disconnected subsequent to disconnecting other electrical connections when disconnecting the amplifier assembly from the handle assembly. Such arrangement promotes device safety as it mitigates a likelihood of static buildup or an unintended closed circuit insofar as the availability of a ground connection is maintained until other electrical connections are opened between a handle assembly and an amplifier assembly.

System checks:

[0205] In embodiments, the handle assembly is configured to perform one or more system self-checks. In some cases, a system self-check is performed prior to activating the oscillator. For example, when a user initiates engaging or activating the oscillator, the handle assembly is configured to automatically first perform a self-check. System selfchecks of interest include, for example, detection of leaks from an energy source; e.g., determination of whether a leak exists within the handle assembly or one or more components external to the handle assembly. Embodiments of handle assemblies are configured to perform system checks associated with confirming a correct or expected voltage and current are present; confirming a voltage or current are within acceptable ranges; confirming electrical grounding is present; confirming a pre-programmed memory chip response is as expected or as specified; confirming zero or maximum cycle count confirmation; confirming a pressure sensor feedback is as expected or as specified; confirming an occurrence of displacement and/or change in voltage and/or current (e.g., from a displacement sensor such as a Hall sensor) is as expected or as specified when fluid (gas or liquid) pressure is applied or removed (i.e., whether an expected response is observed on a displacement sensor such as a Hall sensor when pressure is applied to, or removed from, the diaphragm). In embodiments, the handle assembly may be configured to perform system checks itself or may be configured to do so in conjunction with an amplifier assembly itself configured to perform or facilitate such system checks. In certain embodiments, the amplifier assembly may be configured to perform system checks itself and transmit results of such system tests to a handle assembly or other aspects of the system, such as an operably connected computing device or computer tablet or the like.

[0206] As described, embodiments of handle assemblies are configured to be releasably engaged with embodiments of amplifier assemblies, such that the handle assembly is operably connected with the amplifier assembly. Such operable connection allows the transmission of energy from the handle assembly to the amplifier assembly. In some cases, such operable connection further allows electrical connections between the handle assembly and the amplifier assembly, i.e., the joining of electrical connectors on the handle and amplifier assemblies. Embodiments of handle assemblies of the invention may comprise one or more safety features to ensure proper connection of the system is established and prevent operation when handle assembly and amplifier assembly are not connected properly, or one or more other safety aspects configured to prevent certain behaviors of the handle assembly and/or amplifier assembly and/or other aspects of systems of the invention. In particular, such safety aspects may be configured to prevent the operation of the handle assembly and/or amplifier assembly when the handle assembly is not releasably engaged or operably connected with the amplifier assembly, i.e., is not connected in a specified orientation that enables the safe transmission of energy from the handle assembly to the amplifier assembly. Such safety features may comprise, for example, interlock mechanisms. In embodiments, a handle assembly may comprise an interlock mechanism configured such that the handle assembly cannot transmit energy when an amplifier assembly is not properly connected or attached to the handle assembly. When present, such an interlock mechanism may be configured to prevent, for example, an embodiment of a handle assembly from transmitting energy to an amplifier assembly if the amplifier assembly appears to be not functioning correctly. For example, the handle assembly may be configured to expect a specified output from a displacement sensor (e.g., Hall sensor) attached to a diaphragm of the amplifier assembly when a specified amount of energy is transmitted by the handle assembly. When such specified displacement of the diaphragm does not occur, the handle assembly may be configured to indicate an error state and cease transmission of energy to the amplifier assembly. [0207] In some embodiments, such interlock mechanism is configured such that energy cannot be transmitted from the handle assembly to an amplifier assembly when electrical connections between the handle assembly and amplifier assembly are not connected, e.g., specified circuits are open, or a common ground is not connected or available.

[0208] In other embodiments, the handle assembly comprises an interlock mechanism comprising orienting elements, such as keying elements, configured such that the amplifier assembly and handle assembly can be releasably engaged with each other only in specified orientation that facilitates a connection between, e.g., a hydraulic system, e.g., pressurized gas, as well as electrical connections.

User Interface:

[0209] Handle assemblies may comprise user interface features, e.g., for use by an operator of the handle assembly and/or the system of which the handle assembly forms a part. Such features may comprise input and/or output features; i.e., for receiving information from or conveying information to a user, e.g., an operator.

[0210] In some cases, the user interface of the handle assembly comprises input devices or operator controls to facilitate treatment, such as, for example, one or more buttons, i.e., operator controls. For example, the user interface of the handle assembly may comprise an operator control for initiating an oscillator of the handle assembly. When present, an input device may comprise a single button or a plurality of buttons configured for receiving/reading/detecting user, e.g., operator, feedback or control information. The input features, e.g., one or more buttons, may be located in any convenient location on the exterior of the handle assembly, e.g., may be located in a position selected to promote proper usage of such input feature, or in a difficult to access location in the event the, e.g., button is for use on in infrequent circumstances and/or to avoid pressing such button mistakenly.

[0211] In embodiments, the user interface of the handle assembly comprises output devices, such as one or more lights, such as LED lights. Embodiments of output devices may comprise any visual or tactile elements to convey information to the operator, such as, for example, any type of illumination or light, such as LED lights. In embodiments, lights, such as LEDs, may be used to convey information to the user, e.g., operator, or to illuminate, i.e., highlight, certain sections of the amplifier assembly or otherwise convey information about the state of the handle assembly or amplifier assembly or other aspects of a system of which the handle assembly forms a part. In certain embodiments, the one or more lights (e.g., LEDs) may be integrated into one or more input devices, e.g., buttons, as described above. In other embodiments, the one or more lights (e.g., LEDs) may be multi-colored (i.e., wherein various current inputs create different colors). When different color lights are employed, the different colors may be used to provide information to the user, e.g., operator, e.g., indicative of various conditions or information. In other embodiments, one or more lights may emit various colors to indicate various conditions or information, and/or the one or more lights (e.g., LEDs) may be integrated into the distal interface of the handle assembly and/or integrated into aspects of the amplifier assembly; e.g., the handle assembly and the amplifier assembly may comprise lights configured for use in connection with orienting or positioning the two assemblies relative to each other or to signal a proper connection for operation.

Housing-.

[0212] Embodiments of the handle assembly further comprise a housing, wherein the manifold is present in the housing, and, when present, other aspects of the handle assembly such that disparate components of the handle assembly may be present in a single housing. Such housing may substantially cover the manifold as well as other components of the handle assembly, as desired. In embodiments, the housing is configured to cover and protect components held therein, i.e., protect internal components from exposure to the environment and/or from wear and tear caused by the introduction of foreign objects. While the form of the housing may vary, in some cases, the housing comprises one or more snap fit shells configured to substantially enclose the manifold as well as other components of the handle assembly, as desired.

[0213] In embodiments, the housing comprises a clamshell shape configured to enclose the manifold as well as other aspects, as desired, and to offer mechanical, electromagnetic, electrical, debris, and fluid protection to components inside the housing of the handle assembly. [0214] In embodiments, the housing may be configured to provide a unit that is configured to be hand-held. In such instances, the hand-held component, e.g., hand-held handle assembly, is designed to be held and operated in a single adult human hand. In embodiments, the housing may also be configured to improve the grip for a user, e.g., an operator.

[0215] In other embodiments, the housing is configured to act as a strain relief to ensure that the junction between the handle and the coupler assembly or, e.g., an element of the coupler assembly configured to operably connect the handle assembly and energy source is not damaged.

[0216] In certain instances, the housing can be injection molded using rigid, high-impact strength thermoplastics to prevent damage to the handle assembly or its internal components.

[0217] The housing may be configured to secure it to a specific “home” location. The housing may comprise one or more features to facilitate storing the handle assembly when not in use. For example, in some embodiments, the handle assembly may comprise one or more features to facilitate storing the handle assembly in, for example, a slot on a console to which the handle assembly is connected so that the handle assembly can be protected when not in use. In other embodiments, the handle assembly, or the housing thereof, comprises a magnetic latch in which ferromagnetic plates are integrated into the handle assembly housing and corresponding magnetic plates and a shaped slot are integrated in a locating feature. When such an embodiment of a handle assembly and such a storage feature come into close contact, the magnetic plates and slot align the handle assembly and/or the housing thereof into its appropriate location and hold the handle assembly in place when not in use.

[0218] As described herein, the housing of the handle assembly and/or the distal interface of the handle assembly and/or other aspects of the handle assembly may be configured to facilitate interfacing with an amplifier assembly. In an embodiment, openings (e.g., two, three, four, five or more openings) on a surface of the distal interface (e.g., a surface substantially normal to the long axis of the handle assembly) or on the housing of the handle assembly may be configured to receive mating and locking arms or snaps or other elements of a keyed interface, as convenient, of an amplifier assembly. Such openings may be through-wall or blind holes with a circular or oblong shape. Such openings may have grooves that compress snaps or snap fits or flexible arms of the amplifier assembly during insertion of the amplifier assembly into the receptacles. Edges of such openings may retain the snaps or snap fits or flexible arms while operating the handle assembly and the amplifier assembly, e.g., during pulsatile energy transmission. In some embodiments, retaining the handle assembly’s orientation and operable connection to an amplifier assembly may comprise one or more of a screw, mechanical, magnetic, or electromechanical latch, push-to-connect, or the like, which elements may be present on the distal interface of the handle and/or the housing of the handle assembly and/or other aspects of the handle assembly.

[0219] Additional details regarding aspects of, or components relevant to, handle assemblies that may be incorporated into, or used in conjunction with, embodiments of the present invention are provided in United States Patent No. 1 1 ,464,949; pending PCT Application Serial No. PCT/US2020/055458; United States Application Serial No. 63274832; pending PCT Application Serial No. PCT/US2022/014785; United States Application Serial No. 63238381 ; pending PCT Application Serial No. PCT/US2022/040586; United States Application Serial No. 63346703; pending PCT Application Serial No. PCT/US23/23533; United States Application Serial No. 63346704; pending PCT Application Serial No. PCT/US23/22685; and United States Application Serial No. 63444414; the disclosures of each of which are herein incorporated by reference.

[0220] Various aspects of handle assemblies of the invention being generally described above, elements of handle assemblies are now further reviewed in the context of specific embodiments.

Specific Embodiments:

[0221] A handle assembly in accordance with an embodiment of the invention is depicted in FIGS. 8A-F. FIGS. 8A-F depict an embodiment without a housing in place such that internal components are more easily visualized. [0222] Shown in FIG. 8A is an isometric view of handle assembly 800 with a relatively distal region of handle assembly 800 appearing on the left-hand side of the figure and a relatively proximal region of handle assembly 800 appearing on the right-hand side of the figure.

[0223] Handle assembly 800 comprises distal interface 810. As described herein, handle assemblies of interest interface with amplifier assemblies such that distal interface 810 meets, and operably connects with, a corresponding interface of the amplifier assembly (i.e., a proximal interface of the amplifier assembly), for example proximal nose 210 shown in FIG. 2A.

[0224] Keying element 815 is positioned and shaped to align handle assembly 800 with a corresponding keying element 227 (i.e., keyway) of an amplifier assembly 200 shown in FIG. 2A. Such keying features facilitate operably connecting handle assembly 800 with an amplifier assembly and circumferentially, radially and longitudinally aligning such assemblies.

[0225] Also located in an interior region of distal interface 810 is bore 820. Bore 820 is an output of handle assembly 800, i.e., configured to output energy, e.g., pulsatile energy or static energy in the form of, e.g., high-pressure gas. Bore 820 is configured to interface with, and operably connect with, an amplifier assembly, and in particular, a high-pressure connector 223 of an amplifier assembly 200.

[0226] Manifold 830 of handle assembly 800 is operably connected to an energy source through coupler assembly 850. Manifold 830 is configured to controllably transmit energy to distal interface 810, i.e., bore 820 thereof. Coupler assembly 850 is located in a relatively proximal region of handle assembly 800 and is configured to be operably connected to an energy source. As seen in handle assembly 800, the pathway from coupler assembly 850 to bore 820 is substantially linear, which configuration reduces energy dissipation as compared with a relatively more circuitous path. Receptacles 825 configured to receive snap fit flexible arms of an amplifier assembly are located on opposite sides of distal interface 810.

[0227] FIG. 8B depicts a distal view of handle assembly 800. Distal interface 810 comprises bore 820 with keying element 815 (i.e., key) above. Keying element 815 has rounded outer edges, which feature facilitates aligning keying element 815 (as well as distal interface 810 and bore 820) with corresponding keying elements 227 and high- pressure connector 223 of an amplifier assembly 200. Receptacles 825 are present on either side of distal interface 810.

[0228] FIG. 8C depicts a top view of handle assembly 800. The length of distal interface 810 is illustrated in this view. Manifold 830 is shown above and connected to distal interface 810 in this view. Above manifold 830 is coupler assembly 850. Coupler assembly is operably connected to an energy source (not shown). The substantially direct line from coupler assembly 850, where energy is input into handle assembly 800, to distal interface 810, where energy is output from handle assembly 800, is illustrated in this view.

[0229] FIG. 8D depicts a cutaway top view of handle assembly 800. The depth of a central region of distal interface 810 is illustrated in this view. Bore 820 is located in a relatively central region of distal interface 810. Manifold 830 comprises an oscillator, which in handle assembly 800 is solenoid 835 comprising a plunger that moves between two positions, the first connecting the output of coupler assembly 850 with bore 820, and the second where the output of coupler assembly 850 is not connected to bore 820. That is, in a first position of solenoid 835, energy received form an energy source via coupler assembly 850 is transmitted through handle assembly 800 such that it is output at bore 820 to a connected amplifier assembly, and in a second position of solenoid 835, energy received form an energy source via coupler assembly 850 is exhausted and not output at bore 820 to a connected amplifier assembly.

[0230] FIG. 8E depicts a side view of handle assembly 800. Distal interface 810 is shown at the bottom of the figure, with manifold 830 shown above distal interface 810, and coupler assembly 850 above manifold 830.

[0231] FIG. 8F depicts a cutaway side view of handle assembly 800. Keying element 815 (i.e., key) is located within distal interface 810. Bore 820 is also located within distal interface 810. The fluidic connection between bore 820 and an output of solenoid 835 of manifold 830 is depicted in this cutaway view. The fluidic connection between solenoid 835 of manifold 830 and an output of coupler assembly 850 is also depicted in this cutaway view. [0232] FIGS. 9A-F depict a handle assembly according to an embodiment of the invention. In FIGS. 9A-F, elements having the same or similar reference numerals have the same or similar features as corresponding elements in FIGS. 8A-F, unless explicitly stated otherwise.

[0233] FIG. 9A depicts a distal-side view of handle assembly 900. FIGS. 9B-C depict views of handle assembly 900 from perspectives along the long axis of handle assembly 900. Handle assembly 900 is depicted with housing 990 in place on handle assembly 900. FIGS. 9D-E depict isometric views of handle assembly 900 with a relatively distal side of handle assembly 900 shown on the left-hand side of the figure, and a relatively proximal side of handle assembly 900 shown on the right-hand side of the figure. FIG. 9F depicts a cutaway side view of handle assembly 900.

[0234] Distal interface 910 is present on a distal face of handle assembly 900. Receptacles 925 for retention snaps of flexible arms of an amplifier assembly are present on either side of distal interface 910. Bore 920 is present in a central region of distal interface 920 and is configured such that a high-pressure connector of an amplifier assembly can engage with it. Keying feature 915 is also present within distal interface 910 and configured to engage a corresponding keying feature of an amplifier assembly.

[0235] Housing 990 substantially covers handle assembly 900 with aspects of distal interface 910 exposed as well as a pathway for coupler assembly 950. Grip points 992 comprise a textured surface of housing 990 configured for manually manipulating handle assembly 900 and are present on either side of handle assembly 900. Button 996 is present in a central region of handle assembly for use controlling handle assembly, e.g., engaging solenoid 935 of manifold 930. Button 996 is surrounded by LED lights 994 for providing output to a user (e.g., green lighting indicating handle assembly 900 is operating without an error versus red lighting indicating handle assembly 900 is in an error state versus unilluminated when handle assembly 900 is off).

[0236] FIGS. 9E-F show additional aspects of handle assembly 900. Coupler assembly 950 comprises input and exhaust tubes 955 present at a distal region of handle assembly 900. Input and exhaust tubes 955 are operably connected to an energy source (not shown) as well as an exhaust mechanism for safely receiving exhaust. Manifold 930 comprises an oscillator that is solenoid 935 that exhausts energy when solenoid 935 is in an “off” position. When solenoid 935 is in an “on” position, energy is conveyed through manifold 930 of handle assembly 900 and output at bore 920 of distal interface 910. Connectors 957 are present on the proximal ends of input and exhaust tubes 955.

SYSTEMS FOR IMPARTING PULS TILE ENERGY

[0237] As reviewed above, systems for imparting pulsatile energy are provided. Aspects of systems include: an amplifier assembly, such as amplifier assemblies described herein, and a handle assembly, such as amplifier assemblies described herein. Some embodiments of systems further comprise a console assembly comprising an energy source operably connected to the handle assembly.

[0238] Systems of the invention, or components thereof, may be configured to be reusable or single use, as desired. In cases where a system of the invention (or aspects thereof) is reusable and could contact a patient area, such embodiment can be configured to be covered in a disposable, sterile sleeve or bag such that the system may be used while not contaminating a sterile field of an operating room.

Console Assembly.

[0239] In embodiments, systems of the present invention include a console assembly. The console assembly, also referred to as a console unit or console subsystem, is used in embodiments of systems according to the present invention to generate the required power and control for treatment of, for example, cardiovascular tissue using the system. [0240] Embodiments of console assemblies of systems according to the present invention include an energy source. Energy sources of embodiments of the invention are configured to provide energy, which may be regulated as desired by a regulator. Any convenient energy source may be employed, where examples of energy sources include voltage sources, pressure sources, electromagnetic sources, electric field sources, chemical sources, and the like. In some embodiments, the energy source is a pressure source, where examples of suitable pressure sources include, but are not limited to: compressed gas cylinders, compressors and the like. Where desired, the energy source may be operably coupled to a regulator, which serves to modulate energy from the energy source to a suitable form so that it may be further acted upon, e.g., by an oscillator of a manifold assembly. For example, where the energy source is a high- pressure gas source, the regulator may serve to regulate the pressure of the gas to a suitable value that can be input to an oscillator. In addition to positive energy sources (e.g., high-pressure gas), energy sources of interest may also include a negative potential compared with a reference or standard potential, e.g., an energy source configured to provide a vacuum potential compared to standard atmospheric conditions.

[0241] In some embodiments, the console assembly comprises more than one energy source. In embodiments that comprise more than one energy source, the energy supplied by each energy source may all be of the same type or may be a combination of different energy types. For example, each energy source may be a pressure source (at the same or different potential levels), or, alternatively, one energy source may be a pressure source and another energy source may be a voltage source.

[0242] In embodiments, console assemblies may further comprise one or more regulators (i.e., power regulators), an output port and a controller. With respect to power regulators, as described above, in embodiments, the energy of the energy source may be regulated from a first, input energy, to a second energy, e.g., an energy that is suitable for transmitting to an oscillator of the manifold assembly and ultimately for treatment of, for example, cardiovascular tissue. The energy of the energy source may be regulated to a pre-determined value, a user-set value or may be adjusted according to a variety of feedback inputs that occur during treatment. In some cases, the energy of the energy source may be dynamically regulated based at least in part on conditions related to treatment involving imparting pulsatile energy to tissue, e.g., cardiovascular tissue, e.g., based on changes in tissue compliance during treatment, as described herein. In some cases, the energy of the energy source may be regulated in real time or substantially in real time. In certain embodiments, the energy of the energy source may be adjusted to an optimal value for a certain treatment. For example, the energy of the energy source may be adjusted to an optimal value for treatment of a diseased cardiovascular tissue versus diseased peripheral tissue. In some cases, one or more inputs from one or more of the console assembly, the amplifier assembly, the handle assembly or from a source external to the system (e.g., other measurements regarding a subject, such as imaging of a subject) may be used to determine an optimal treatment condition, e.g., output energy of the energy source appropriate for the desired treatment, and then to adjust to that condition.

[0243] In embodiments that comprise a regulator (i.e., a power regulator or potential regulator) configured to regulate the energy of the energy source, such a regulator may be a passive (i.e., preset or user-adjusted regulator) or an active regulator (i.e., a regulator that is controlled with, for example, an electrical impulse or other dynamic signal from, e.g., a controller). Regulators of interest may comprise regulators typically used for fluidic regulation such as a directional or diaphragm valve, electrical regulation such as a voltage regulator, optical power regulation or the like. In embodiments that comprise more than one energy source, the potentials of the various energy sources may be regulated together or separately.

[0244] In embodiments, the regulated and/or unregulated energy (e.g., potential energy) from the energy source is output through an output port operably coupled to the manifold of a handle assembly of the system. Any convenient output port, such as commercially available connectors, such as pneumatic, hydraulic, electrical or optical connectors, may be employed in embodiments. In certain instances, the unregulated or regulated potential energy may be converted to another energy form prior to or, in some cases, after the energy is passed or otherwise transmitted to the manifold of the handle assembly.

[0245] In some cases, the console assembly may include more than one physically separate or connected units, i.e., each, a console unit, that may be operably interconnected (e.g., electrically, fluidically, using radio frequency (RF) or the like). That is, the console assembly may comprise a unitary assembly or two or more distinct, operably connected units.

[0246] In some instances, at least some of the console assembly components are present in a unit that is configured to be hand-held or manipulated, e.g., moved, by hand. While the form factor of such a unit may vary as desired, in some instances, such units may be configured substantially as a rectangular box having height ranging from 10 to 100 cm, such 20 cm to 30 cm, width from 5 to 100 cm, such as 10 to 20 cm and depth ranging from 10 to 100 cm, such as 20 to 30 cm, and a mass ranging from 1 to 20 kg, such as 5 to 8 kg. [0247] In an embodiment, a console assembly may include a first console component that houses an energy source, e.g., a pressure source, and regulator and actuator for the pressure source, e.g., a manipulatable button. The console assembly may include an electrical connector for providing electrical connection to various other components of the system, as desired. For example, an electrical connector may be used to receive data regarding, for example, balloon pressure or volume measurements, and to provide power to sensors configured to collect such data regarding treatment using the system.

[0248] In some instances, at least some of the console assembly components are present in a mountable unit that is configured to be positioned or fixed on or proximal to an operating table near a subject, i.e., a patient, so that an operator, e.g., a physician, does not need to physically interact with the console assembly (for example, the operator does not need to be physically present in an operating room and can communicate with the system via a remote control at a distance) to treat the subject. In such instances, the mountable unit is designed to be easily clamped, fixed, or independently stable on, or proximal to, the operating table and can be operated by a distal control unit. In such instances, the mountable unit may include a communicator that provides for communication between the console assembly and other controllers present within or external to the system, which may be implemented by any desired hardware and/or software configuration and may be configured to communicate using wired or wireless protocols.

[0249] Console assemblies and/or energy sources thereof that are employed in systems of the invention may be configured to be reusable or single use, as desired. Console assemblies employed in systems of the invention may be configured to receive a sterile sleeve such that the console assembly may be used while not contaminating a sterile field of an operating room.

Controller.

[0250] Embodiments of the console assembly of systems according to the present invention include a control subsystem also referred to as a controller or control assembly. Embodiments of systems may utilize a controller to control the amount and duration of energy transmitted to tissue, e.g., cardiovascular tissue. In some instances, embodiments of systems may utilize a controller to measure the effect of treatment on cardiovascular tissue, such as a degree of disruption of calcified tissue, e.g., cardiovascular tissue compliance, as described herein. In embodiments, the control assembly may be present in other components of the system, such as a handle assembly, or may be distributed among a plurality of components of the system, such as a console assembly and a handle assembly, for example.

[0251] In embodiments, the control subsystem may be connected to, receive information from, and/or adjust (i.e., control) aspects of one or more of the console assembly (such as a pressure source or a regulator), the handle assembly (such as an oscillator) or the amplifier assembly. The control subsystem may also be configured to receive information from, and/or control, external systems such as an electrocardiogram (ECG), an intravascular or external pressure monitor, a blood volume sensor, patient vitals sensors or an imaging system such as an imaging system utilizing fluoroscopy, intravascular ultrasound (IVUS) or optical coherence tomography (OCT). Further, the control subsystem may comprise multiple control units interconnected such that one or more of the units synchronize and communicate with each other.

[0252] In some cases, the control subsystem (or control units that comprise the control subsystem) may be configured to communicate with components of the system such that energy transmitted via the amplifier assembly is appropriate, i.e., appropriate for a particular treatment involving applying pulsatile energy to tissue, e.g., cardiovascular tissue.

[0253] In an embodiment, the controller is configured to receive a treatment plan, i.e., control instructions related to a specific treatment for a specific treatment of a subject. A treatment plan may include, for example, a specified potential amount, a frequency or duty cycle of the oscillator of the handle assembly. In addition, a treatment plan may include information about the type of pulsatile balloon or other tissue-engaging element to be employed, such as a size or orientation. Further details regarding treatment plans, control systems and updating the behavior of catheter-based procedures based on data collected about the procedure are described in United States Application Serial No. 63346704; and pending PCT Application Serial No. PCT/US23/22685; the disclosure of which is incorporated herein by reference. [0254] In embodiments, a controller may be configured to provide feedback to an operator of a system of the present invention in any convenient manner. In some cases, the controller is configured to provide tactile feedback to an operator by, for example, vibrating. For example, the controller may be configured to cause a handle or other interface with an operator of a system to vibrate upon a relevant change or determination, such as measurement of a sensor, for example, changes in compliance of the cardiovascular tissue. Such tactile feedback may be used in connection with indicating to an operator of an embodiment of a system to change a configuration of the system.

[0255] In embodiments, a control assembly is configured to implement a system workflow, i.e., to interact with an operator such that the system can be used to deliver pulsatile energy as specified by the operator for use in a procedure, for example. Control assembly may comprise a hardware device, such as one or more processors with one more memories operably connected thereto with instructions thereon which, when executed by the processor(s), cause the processor(s) to implement such a system workflow. Processors and memory devices of interest include commercially available general purposes processors or controllers or microcontrollers or application specific integrated circuits or the like.

[0256] FIG. 10A depicts flow diagram 1000 comprising a system activity diagram showing software states of a control assembly of a system, in each case according to embodiments of the present invention. Workflow 1000 depicts system controller states and transitions moving therebetween from Startup States 1010 through Not Ready States 1020 to Ready States 1030. Such system controller states and transitions therebetween are associated with certain specified interactions with a user, i.e., operator, such as when an operator turns on a system under certain circumstances within a Startup State 1010. Such system controller states and transitions therebetween are also associated with system functions and system behavior, such as the system performing a prime check under certain circumstances within a Ready State 1030.

[0257] In particular, flow diagram 1000 describes how a system according to an embodiment of the invention interacts with its various components. At startup corresponding to a Startup State 1010, the user interacts with the system by connecting power and turning the system on. The console and handle (if/when attached), in each case of the system, perform internal safety checks. These safety checks may include, for example, electrical and signal integrity checks; display integrity checks; pneumatic input, output, exhaust, and connection tests; and/or maintenance checks. During or after such checks are performed, an operational screen may be displayed to provide the user with feedback on the operational state of the system. One request the system might provide to the user is to connect an energy source (in this case a CO2 tank) to the system and pressurize. Once pressurized, the system senses the pressure via continuous checks to ensure pressure input integrity. Further, the user is prompted to prepare the catheter, sheath the handle in a sterile sleeve, and then to install the catheter when ready. These actions are part of Not Ready State 1020 of flow diagram 1000 corresponding to system controller states wherein the system is not ready to initiate pulsatile energy or otherwise conduct a procedure using the system.

[0258] When the system has an amplifier assembly and/or catheter assembly operably connected or otherwise attached to the system (e.g., such as an operable connection between a handle assembly and amplifier assembly, as described herein), the system is configured to recognize the amplifier assembly and/or catheter assembly and performs pre-treatment safety checks. That is, the control assembly may be configured (e.g., comprise software programmed to perform) such safety checks related to aspects of the system. Such amplifier assembly and/or catheter assembly may be referred to as disposable or disposable components in cases where the system is configured to reuse certain components (e.g., a handle assembly or a console assembly) but not reuse (i.e., dispose of) such amplifier assembly and/or catheter assembly between uses or between procedures performed by the system.

[0259] Such safety checks related to the disposable components, i.e., amplifier assembly and/or catheter assembly, include, for example: electrical integrity checks; minimum or maximum pressure checks; pneumatic integrity checks including inlet, outlet and exhaust; lifecycle and prior use and/or connection tests; prime check; indication or use-case check; and/or burst pressure rating check.

[0260] Once the controller receives feedback, such as sensor data, consistent with confirmation that the amplifier assembly and/r catheter assembly passes such safety checks, flow diagram 1000 transitions a Ready State 1030, in which the system prompts the user to prime the catheter and depress a button, e.g., a button present on a handle assembly, when ready for treatment, i.e., when ready to initiate treatment. When such button is depressed or other input is received from the user indicating a procedure should commence, the system proceeds through flow diagram 1000 to perform additional checks, including, for example: electrical integrity checks; minimum or maximum pressure checks; pneumatic integrity checks including inlet, outlet and exhaust; lifecycle and prior use and/or connection tests; prime check; indication or use-case check; burst pressure rating check; and/or initial pressure test. The control assembly may be configured to perform such checks simultaneously or substantially simultaneously or continuously or repeated on an ongoing basis.

[0261] In addition, the control assembly may be configured such that prior to, during, or after treatment using the system, the system tracks and logs various system states and sensor values for continuous learning, maintenance checks, data tagging, or the like. Such data may be stored in a local or distributed memory or may be transferred to an external computing device, such as a computer table, or uploaded to cloud-based storage, for example.

[0262] FIG. 10B depicts flow diagram 1000B of another embodiment of software control of a system according to the present invention.

[0263] An exemplary graphical user interface screen is shown in FIG. 10C according to embodiments of the present invention. In embodiments of systems of the invention, one or more elements may comprise a display screen. In certain embodiments, console units comprise a display screen and associated hardware and software configured to present graphical user interface 1050. Graphical user interface 1050 is separated into a plurality of boxes or panes. Treatment pane 1054 of graphical user interface 1050 is included to provide count down for the deployment therapy and timeout information (e.g., a forced pause in the deployment of therapy). When the system is able to treat, i.e., to perform a procedure, i.e., to generate and transmit pulsatile energy, text in the treatment pane 1054 appears a specific color, e.g., white; when the system is unable to treat, text in the treatment pane 1054 appears a different color, e.g., grey (but is still visible). When the system is engaged to deploy therapy, there is a countdown displayed in treatment pane 1054 from the maximum allowed continuous treatment time to zero; in treatment pane 1054, the countdown time is 45 seconds remaining. After treating for the full maximum allowed treatment time, treatment pane 1054 displays a countdown to reflect a system timeout where therapy cannot be deployed. The top of treatment pane 1054 displays the text “Run,” which can be updated to reflect the timeout count as well.

[0264] Priming pane 1053 of graphical user interface 1050 is highlighted when the system directs an operator or user to prime the catheter assembly of the system. When the system is not directing an operator to prime the catheter assembly, the displayed gauge and associated text in priming pane 1053 is displayed in a different color or intensity, e.g., is grayed out, and, in some cases, the priming pressure value text is replaced with another symbol,

[0265] System state pane 1051 of graphical user interface 1050 is updated to provide information of the system status and/or a software state and/or controller state. Graphical user interface 1050 may also be configured to display a logo in system state pane 1051 . [0266] Total catheter life pane 1055 of graphical user interface 1050 includes a count-up bar from zero to the total allowable treatment life of the catheter of the system. In embodiments of graphical user interface 1050, such bar is filled in a specified color, e.g., yellow, with a dot in such color, e.g., yellow, progressing from the left to the right until the dot reaches the vertical line on the right hand side of total catheter life pane 1055.

[0267] When the catheter of the system is used without uninstalling it, total catheter life pane 1055 will display a gap between pulse cycles. In embodiments, a pulse cycle is a continuous deployment of therapy (i.e., the interval of time an operator presses the button (i.e., a button on a handle assembly of the system configured to cause the system to initiate treatment) for before releasing). In embodiments, the maximum pulse cycle time is the maximum allowed continuous treatment time (the amount corresponds to the 45 seconds indicated in treatment pane 1054). If an operator uninstalls and reinstalls a catheter assembly that has been pulsed, such gap or gaps will not be present but the bar of catheter life pane 1055 will be displayed in a specified color, e.g., yellow, with the dot in a specified location. In embodiments, the system may be configured not record when a pulse cycle takes place to the catheter assembly software but instead the total number of pulses applied by the system. [0268] Notification pane 1056 of graphical user interface 1050 provides additional information about use or state or status of the system for the operator, i.e., the user. In embodiments, the color of the notification pane 1056 is reflective of the system status; i.e., the color of notification pane 1056 may change based on system status or state. In embodiments, the color of notification pane 1056 may be selected to match the color of an LED of a button of a handle assembly, when present.

[0269] Subsystem status pane 1052 of graphical user interface 1050 provides a single location for all information on each subsystem of the system (e.g., operational and/or error status of the different subsystems of the system). Such information is distributed a catheter sub-pane, a handle sub-pane, a console sub-pane and a CO2 tank sub-pane.

[0270] In a catheter sub-pane of subsystem status pane 1052, a color of the catheter icon indicates a status of the catheter. For example, in embodiments, the catheter may appear gray to indicate no catheter connected; green to indicate catheter is operational; and orange to indicate an error has occurred and/or instruct the operator, i.e., user, to replace the catheter. In embodiments, a catheter sub-pane of subsystem status pane 1052 may indicate connected/disconnected based upon an installation state of a catheter assembly of the system. In embodiments, a balloon length and/or diameter information may be updated based upon what information is retrieved from the catheter assembly (i.e., the amplifier assembly of the system has a memory that can be read by the system. In embodiments, the balloon status may have three states (i.e., unprimed, primed or delivering therapy), and such may be reflected in this aspect of graphical user interface 1050. In embodiments, a pulse count value is updated when the system is deploying therapy, and this value can coincide with values displayed in total catheter life pane 1055. [0271] In a handle sub-pane of subsystem status pane 1052, a color of the handle icon indicates a status of the handle assembly of the system. For example, the handle may be displayed as a specified color, e.g., green, to indicate the catheter is operational, or another color, e.g., orange, to indicate an error has occurred or that the handle assembly is not intended to be disconnected in normal usage, or still another color, e.g., red, to indicate an internal error has occurred and the operator should contact a service for support. The handle sub-pane of subsystem status pane 1052 may further provide a connection status of the handle assembly. [0272] In a console sub-pane of subsystem status pane 1052, a color of the console icon indicates a status of the console assembly of the system. For example, the console may be displayed as a specified color, e.g., green, to indicate the console is operational, or another color, e.g., orange, to indicate an error has occurred, or still another color, e.g., red, to indicate an internal error has occurred and the operator should contact a service for support. The console sub-pane of subsystem status pane 1052 may further provide a connection status of the console assembly.

[0273] In a CO2 tank sub-pane of subsystem status pane 1052, the graphical user interface 1050 is configured such that a tank icon fill level reflects tank pressure. In embodiments of a tank sub-pane of subsystem status pane 1052, a specified color, e.g., green, indicates pressure is a sufficient level; another specified color, e.g., orange, indicates pressure low such that an operator, i.e., user, can proceed with use of the system but will need to replace an energy source, e.g., CO2 tank, soon. Still another color, e.g., red, indicates pressure is too low and an energy source, e.g., CO2 tank, requires replacement.

[0274] Graphical user interface 1050 is further configured or designed such that error states will be displayed as popups, e.g., popup boxes on the display. In embodiments, the color of the popup reflects the urgency of the notification. For example, in embodiments, a specified color, e.g., blue, popup/notification is associated with a normal work item directing user to execute a task; another color, e.g., orange, popup/notification is associated with a requirement for user action; text may be presented in the popup to provide guidance for the operator to correct the error state. Still another color, e.g., red, indicates an internal error has occurred and the operator should contact a service for support. In embodiments, notification pane 1056 reflects a color associated with a system state; e.g., a green notification pane 1056 indicates a system state that is ready to deploy therapy and/or is deploying treatment.

[0275] FIG. 1 1 depicts aspects of a system according to an embodiment of the present invention. In FIG. 1 1 , elements having the same or similar reference numerals have the same or similar features as corresponding elements in FIGS. 1A-D, unless explicitly stated otherwise. [0276] System 1 102 comprises handle assembly 1101 shown in transparent isometric view. Handle 1101 is shown oriented relative to amplifier assembly 1100 to illustrate how handle assembly 1101 can be operably connected to amplifier assembly 1 100. Amplifier assembly 1 100 is also shown in a transparent and cutaway isometric view, such that a distal region of amplifier assembly 1 100 is depicted on the right-hand side of the figure. Console assembly 1103 is depicted in a cutaway isometric view. Console assembly 1103 may be operably connected to handle assembly 1101 such that pulsatile energy, e.g., pressurized fluid is transmitted from console assembly 1 103 to handle assembly 1 101. Console assembly 1103 is also connected to CO2 tank 1 104, a source of energy for system 1102.

[0277] FIG. 1 1 also depicts aspects of system 1 102 configured to enable and/or perform system safety checks. Such safety checks are designed to ensure that system 1 102 does not damage downstream components. System 1102 is configured to conduct safety checks related to the follow; i.e., system 1102 has the following safety checks built in: appropriately rated, tank to console connector hose is ensured by utilizing a built-in connector to prevent connection to other gases/tank styles, and pressure check valve is present to prevent user gas exposure during accidental or intentional disconnection of a tank or other energy source; a check valve inlet is utilized to prevent pneumatic system contamination; a mechanical regulator with preset inlet, tank and/or outlet pressure sensor is utilized to ensure proper inlet and outlet pressure; electronic regulator/proportional control valve is utilized to allow system 1102 to control outlet pressure (in certain embodiments, mechanical and electronic regulators can be combined into a single unit/manifold); a handle pressure sensor is utilized in order to ensure that output of electronic regulator is consistent with pressure in handle; a solenoid cracking pressure is taken into account such that, even if extremely high pressure fluid is passed down stream, the solenoid of console assembly 1103 does not output pressure downstream, but, instead, it vents fluid similar to a pressure relief valve; a solenoid control is utilized such that sensors prevent actuation of solenoid if a handle pressure sensor is out of range, i.e., out of an expected or acceptable range; amplifier 1 100 is configured such that amplifier 1100 signals or otherwise informs system 1 102 (i.e., a controller for system 1 102) of normal treatment pressure, max allowable pressure, and lifecycle of disposable components (e.g., amplifier assembly 1100 and/or a catheter assembly). In cases of a balloon burst, a Hall sensor integrated into a diaphragm of amplifier 1 100 is configured to detect burst and causes hardware in handle 1101 (e.g., a comparator to a known voltage) to prevent further treatment, i.e., to prevent further transmission of energy to amplifier assembly 1100.

[0278] A system for imparting pulsatile energy in accordance with an embodiment of the invention is depicted in FIG. 12. System 1202 includes amplifier subsystem or assembly 1200 and handle subsystem or assembly 1201 . Amplifier subsystem or assembly 1200 and handle subsystem or assembly 1201 are connected such that electrical signals, power or ground as well as pneumatic energy can be transmitted between such assemblies

[0279] Amplifier subsystem 1200 is operably connected to catheter subsystem or assembly 1205. Catheter subsystem 1205 comprises a tissue-engaging element (not shown), such as a distal balloon or heart tissue conforming element, for example.

[0280] Handle subsystem or assembly 1201 is operably connected to console 1203 such that electrical signals, power or ground and pneumatic energy can be transmitted between such components. Console subsystem 1203 receives energy in the form of pressurized gas from gas tank 1204. Console subsystem 1203 is also operably connected to electrical power source 1206.

[0281] System 1202 is depicted in schematic form to show a system deployment diagram. As described, system 1202 has four major subsystems: (1 ) console subsystem 1203, (2) handle subsystem 1201 , (3) amplifier subsystem 1200, and (4) catheter subsystem 1205. Such subsystems work together and with external power 1206 and an energy source 1204 (in this case, pressurized gas) to produce the pulsatile intravascular lithotripsy effect.

[0282] Console subsystem 1203 is configured to manage power, electrical signal, and regulation and setting of energy output. Handle subsystem 1201 is configured to manage the output and exhaust of energy and reading of user inputs to system 1202. Amplifier subsystem 1200 receives output energy from handle subsystem 1201 and converts that energy to a hydraulic shock and guides the shock to catheter subsystem 1205. Amplifier subsystem 1200 also manages and reads several sensors to ensure safe treatment. Catheter subsystem 1205 receives the shock from the amplifier 1 00, transmits it through a catheter tube, and transfers the energy from the distal balloon to the calcium, e.g., a lesion, with minimal attenuation of the input signal.

[0283] Additional details regarding aspects of, or components relevant to, systems for imparting pulsatile energy that may be incorporated into, or used in conjunction with, embodiments of the present invention, including, for example, further details regarding aspects of console units, energy sources, oscillators, regulators, etc., are provided in United States Patent No. 11 ,464,949; pending PCT Application Serial No. PCT/US2020/055458; United States Application Serial No. 63274832; pending PCT Application Serial No. PCT/US2022/014785; United States Application Serial No. 63238381 ; pending PCT Application Serial No. PCT/US2022/040586; United States Application Serial No. 63346703; pending PCT Application Serial No. PCT/US23/23533; United States Application Serial No. 63346704; pending PCT Application Serial No. PCT/US23/22685; and United States Application Serial No. 63444414; the disclosures of each of which are herein incorporated by reference.

METHODS

[0284] Systems of the invention find use in a variety of applications. In some instances, the systems find use in fracturing hardened materials embedded within an elastic conduit. For embodiments presented herein, the present disclosure describes applications related to treating atherosclerotic calcifications within an arterial conduit, such as a coronary or peripheral artery. However, the present system and teachings are not solely limited to atherosclerotic calcifications nor arterial conduits and may be generally applied to other applications as determined by those skilled in the art. For example, this is especially true for circumstances that alter arterial compliance (i.e., vessel compliance of an artery) or for cases that involve medical interventions, such as the presence of a previous stent with subsequent blockage. The compliance of the vessel is altered by the intra-luminal placement of a previous stent. Data and feedback of vessel compliance curves can be used in connection with future therapies as well as for prediction techniques, such as machine learning techniques. [0285] In some instances, the various embodiments of the systems described herein are employed in methods of dynamic balloon angioplasty (DBA), a technique that uses pressure oscillations with a generalized waveform (in some embodiments, harmonic, or frequency-specific, pressure waveform oscillations) to effectively and safely fracture calcified lesions during angioplasty. In some instances, the various embodiments of the systems described herein are employed in methods of assessing vessel compliance in- vivo, a measurable characteristic of blood vessels calculated based on a ratio of the change in vessel volume for a given change in pressure. Systems according to the present invention may be configured to assess vessel compliance by obtaining measurements in vivo of changes in volume at different pressures (or changes in pressure) applied to vessels. Such measurements of vessel compliance can be taken during treatment, for example.

[0286] Methods for imparting pulsatile energy to a tissue are also provided and similarly find benefit in the applications described herein. Methods according to the present invention comprise deploying a system comprising an amplifier assembly and a handle assembly, as described herein, so that a tissue-engaging element operably connected to the system is adjacent to tissue. Components of systems, amplifier assemblies and handle assemblies are described in detail above. By tissue-engaging element, it is meant any treatment-related element capable of receiving pulsatile or static energy in the form delivered by an amplifier assembly. Tissue-engaging elements are configured for use in treating diseased tissue. Tissue-engaging elements of interest include, for example, a distal balloon, such as a compliant or non-compliant distal balloon or modified versions thereof, or a heart-tissue-conforming element.

[0287] Methods according to the present invention further comprise engaging the system in a manner that imparts energy to the tissue. For example, such methods may comprise imparting pulsatile energy to the tissue or imparting static energy to the tissue (i.e., by inflating a distal balloon to a static pressure or volume over a period of time). In embodiments, by imparting pulsatile energy, it is meant repeatedly pressurizing a distal region (e.g., the distal chamber) of the amplifier assembly; e.g., the distal chamber of the distal waveguide is repeatedly subjected to pressure oscillations transmitted from the handle assembly through the amplifier assembly, at any convenient amplitude, frequency, duty cycle and duration. Such pressure oscillations originate from the handle assembly and are transmitted therefrom to the amplifier assembly, as described in detail above in connection with embodiments of systems and amplifier and handle assemblies. Any suitable amplitude, frequency, duty cycle and duration of pressure oscillations may be used, and such may vary.

[0288] The methods may be used for imparting pulsatile energy to tissue locations of any number of different subjects. In some instances, the subjects are “mammals” or "mammalian," where these terms are used broadly to describe organisms which are within the class mammalia, including the orders carnivore (e.g., dogs and cats), rodentia (e.g., mice, guinea pigs, and rats), and primates (e.g., humans, chimpanzees, and monkeys). In some instances, the subjects are humans.

[0289] Further details regarding methods in which embodiments of the invention may be used, including further details regarding dynamic balloon angioplasty (DBA) and vessel compliance, are found in United States Patent No. 11 ,464,949; pending PCT Application Serial No. PCT/US2020/055458; United States Application Serial No. 63274832; pending PCT Application Serial No. PCT/US2022/014785; United States Application Serial No. 63238381 ; pending PCT Application Serial No. PCT/US2022/040586; United States Application Serial No. 63346703; pending PCT Application Serial No. PCT/US23/23533; United States Application Serial No. 63346704; pending PCT Application Serial No. PCT/US23/22685; and United States Application Serial No. 63444414; the disclosures of each of which are herein incorporated by reference.

KITS

[0290] Also provided are kits that include assemblies or systems, or one or more components thereof, e.g., as described above. As such, kits may include, in some instances, one or more of, an amplifier assembly or a handle assembly or a system comprise an amplifier assembly and a handle assembly, in each case, with or without a console and/or an energy source, e.g., a pressure source, or components thereof. The kit components may be present in packaging, which packaging may be sterile, as desired. Components of the kit may be disposable or reusable, as desired. In some cases, kits may comprise a plurality of components including multiple versions of the same component in different sizes, such as, for example, multiple amplifier assemblies or multiple catheters of varying sizes.

[0291] Also present in the kit may be instructions for using the kit components. The instructions may be recorded on a suitable recording medium. For example, the instructions may be printed on a substrate, such as paper or plastic, etc. As such, the instructions may be present in the kits as a package insert, in the labeling of the container of the kit or components thereof (i.e., associated with the packaging or sub-packaging) etc. In other embodiments, the instructions are present as an electronic storage data file present on a suitable computer readable storage medium, e.g., portable flash drive, DVD- or CD-ROM, etc. The instructions may take any form, including complete instructions for how to use the device or as a website address with which instructions posted on the world wide web may be accessed.

[0292] The following exemplary embodiments is/are offered by way of illustration and not by way of limitation.

ADDITIONAL EXEMPLARY EMBODIMENTS

[0293] FIG. 13 shows a prototype exemplary embodiment of proximal nose 1300 of an amplifier assembly according to the present invention. Proximal nose 1300 includes high- pressure connector 1301 . Proximal nose 1300 and high-pressure connector are formed from dissimilar materials (a plastic and a metal, respectively).

[0294] FIG. 14 shows a prototype exemplary embodiment of distal waveguide 1400 of an amplifier assembly according to the present invention. Distal waveguide 1400 comprises a substantially bell-jar shape with proximal face 1401 present on a proximal side of distal waveguide 1400.

[0295] FIGS. 15A-B show a prototype exemplary embodiment of a diaphragm 1500 of an amplifier assembly according to the present invention. Diaphragm 1500 is integrated with a Hall sensor and associated electronics assembly 1501. Hall sensor 1500 comprises probe 1502 located near the center of diaphragm 1500. Diaphragm 1500 comprises a shape with pleats or folds 1503 such that diaphragm is configured to translate between a distal face of a proximal nose and proximal face of a distal waveguide without producing strain on diaphragm 1500.

[0296] FIG. 16 shows a prototype exemplary embodiment of a proximal nose 1600 of an amplifier assembly according to the present invention. Proximal nose 1600 is integrated with electronics package 1602 of diaphragm 1601.

[0297] FIGS. 17A-D show assembly of an amplifier assembly 1700 according to the present invention. Amplifier assembly 1700 includes electronics assembly 1702. Electronics assembly 1702 includes connector plates 1703 oriented on an outer surface of amplifier assembly 1700 such that amplifier assembly 1700 can be reliably associated with a handle assembly (not shown) and such electrical connectors interconnected with corresponding connectors of a handle assembly. Amplifier assembly 1700 also includes pins 1704 inserted through amplifier assembly 1700 in order to compress the diaphragm (not shown) between the proximal nose and the distal waveguide thereby sealing a proximal chamber from a distal chamber. Amplifier assembly 1700 comprises high- pressure connector with O-ring 1705.

[0298] Notwithstanding the appended claims, the disclosure is also defined by the following clauses:

1 . An amplifier assembly, the assembly comprising: a proximal nose, comprising a distal face; a distal waveguide, comprising a proximal face; and a diaphragm compressed between the proximal nose and the distal waveguide thereby sealing a proximal chamber from a distal chamber, wherein the diaphragm is configured to translate between the distal face of the proximal nose and proximal face of the distal waveguide without producing strain on the diaphragm.

2. The amplifier assembly of clause 1 , wherein the proximal chamber is defined by a first volume between the diaphragm and the distal face of the proximal nose. 3. The amplifier assembly of any of the preceding clauses, wherein the distal chamber is defined by a second volume between the diaphragm and the proximal face of the distal waveguide.

4. The amplifier assembly of any of the preceding clauses, wherein the diaphragm is configured to occupy different positions between the distal face of the proximal nose and the proximal face of the distal waveguide.

5. The amplifier assembly of any of the preceding clauses, wherein the diaphragm is configured to occupy different positions between the distal face of the proximal nose and the proximal face of the distal waveguide without producing strain on diaphragm material.

6. The amplifier assembly of any of the preceding clauses, wherein the diaphragm is configured to conform to new shapes and thereby to occupy different positions between the distal face of the proximal nose and the proximal face of the distal waveguide.

7. The amplifier assembly of any of the preceding clauses, wherein the diaphragm is configured to conform to the distal face of the proximal nose in a proximal position of the diaphragm and to conform to the proximal face of the distal waveguide in a distal position of the diaphragm.

8. The amplifier assembly of clause 7, wherein the diaphragm comprises a shape that conforms to the distal face of the proximal nose in a proximal position of the diaphragm and to conform to the proximal face of the distal waveguide in a distal position of the diaphragm.

9. The amplifier assembly of any of the preceding clauses, wherein the diaphragm comprises folds.

10. The amplifier assembly of any of the preceding clauses, wherein the diaphragm comprises pleats.

1 1 . The amplifier assembly of any of the preceding clauses, wherein the diaphragm comprises pleated bellows.

12. The amplifier assembly of any of the preceding clauses, wherein the diaphragm comprises a shape that fits within indentations of the distal face of the proximal nose and within indentations of the proximal face of the distal waveguide. 13. The amplifier assembly of any of the preceding clauses, wherein without producing strain on the diaphragm comprises without producing tension on the diaphragm.

14. The amplifier assembly of any of the preceding clauses, wherein without producing strain on the diaphragm comprises without stretching diaphragm material.

15. The amplifier assembly of any of the preceding clauses, wherein the diaphragm is configured to translate without resistance from diaphragm material.

16. The amplifier assembly of any of the preceding clauses, wherein the diaphragm is configured to translate without applying stress to diaphragm material.

17. The amplifier assembly of any of the preceding clauses, wherein an outer ring of the diaphragm seals an interface between the proximal nose and the distal waveguide.

18. The amplifier assembly of any of the preceding clauses, wherein the diaphragm comprises a circumferential protrusion configured to enable the diaphragm to maintain its seal while translating between the distal face of the proximal nose and the proximal face of the distal waveguide.

19. The amplifier assembly of clause 18, wherein the circumferential protrusion is a T-shaped edge.

20. The amplifier assembly of any of the preceding clauses, wherein the proximal nose comprises a proximal interface located at a proximal region of the proximal nose.

21 . The amplifier assembly of clause 20, wherein the proximal interface comprises a high-pressure connector.

22. The amplifier assembly of clause 21 , wherein the high-pressure connector is in fluidic communication with the proximal chamber.

23. The amplifier assembly of clause 21 , wherein the high-pressure connector is configured to receive high-pressure fluid.

24. The amplifier assembly of clause 21 , wherein the high-pressure connector is configured to receive pulses of high-pressure fluid.

25. The amplifier assembly of any of clauses 23 to 24, wherein the high- pressure fluid comprises a gas. 26. The amplifier assembly of any of clauses 23 to 25, wherein the high- pressure fluid comprises air.

27. The amplifier assembly of any of clauses 21 to 26, wherein the high- pressure connector comprises metal.

28. The amplifier assembly of clause 27, wherein the metal of the high- pressure connector is molded into plastic of the proximal interface.

29. The amplifier assembly of any of clauses 21 to 28, wherein the high- pressure connector comprises an O-ring groove configured to receive an O-ring.

30. The amplifier assembly of clause 29, wherein the high-pressure connector comprises an O-ring disposed on the O-ring groove.

31 . The amplifier assembly of any of the preceding clauses, wherein the proximal interface comprises a keyed face.

32. The amplifier assembly of clause 31 , wherein the keyed face comprises one or more of: a grooved detent, an asymmetrical channel, an oblong shape and a rectangular prism.

33. The amplifier assembly of any of the preceding clauses, further comprising an electrical assembly integrated into one or more of the proximal nose, the distal waveguide and the diaphragm.

34. The amplifier assembly of clause 33, wherein the electrical assembly comprises a plurality of electrical connectors integrated into the proximal interface.

35. The amplifier assembly of any of clauses 33 to 34, wherein the proximal interface is configured such that the electrical connectors make electrical connections perpendicular to a long axis of the amplifier assembly.

36. The amplifier assembly of any of clauses 33 to 35, wherein the electrical connectors comprise a plurality of plates configured to interface with a plurality of ball connectors.

37. The amplifier assembly of any of clauses 33 to 36, wherein the electrical connectors comprise a ground plate that spans the entire length of the plurality of electrical connectors.

38. The amplifier assembly of any of clauses 33 to 37, wherein the electrical assembly comprises circuitry. 39. The amplifier assembly of any of clauses 33 to 38, wherein the electrical assembly comprises memory.

40. The amplifier assembly of clause 39, wherein the memory comprises one or more of: positional sensor readings and pressure sensor readings.

41 . The amplifier assembly of any of the preceding clauses, wherein the distal waveguide comprises a catheter interface located at a distal region of the distal waveguide.

42. The amplifier assembly of clause 41 , wherein the catheter interface is in fluidic communication with the distal chamber.

43. The amplifier assembly of any of clauses 41 to 42, wherein the catheter interface comprises a Luer lock.

44. The amplifier assembly of clause 43, wherein the Luer lock is a floating Luer lock.

45. The amplifier assembly of any of clauses 41 to 44, wherein the catheter interface is configured to receive high-pressure fluid.

46. The amplifier assembly of any of clauses 41 to 45, wherein the catheter interface is configured to receive pulses of high-pressure fluid.

47. The amplifier assembly of clause 46, wherein the high-pressure fluid comprises saline.

48. The amplifier assembly of any of the preceding clauses, further comprising pins configured to hold the distal waveguide compressed against the diaphragm and proximal nose.

49. The amplifier assembly of clause 48, wherein the pins are steel pins.

50. The amplifier assembly of any of the preceding clauses, further comprising a pressure sensor configured to sense fluid pressure within the distal waveguide.

51 . The amplifier assembly of clause 50, wherein the pressure sensor is integrated into the distal waveguide.

52. The amplifier assembly of any of clauses 50 to 51 , wherein the pressure sensor is configured to sense pressure within the distal chamber.

53. The amplifier assembly of any of clauses 50 to 52, wherein the pressure sensor is electrically connected to the electrical assembly. 54. The amplifier assembly of any of the preceding clauses, further comprising a sensor configured to sense to the position of the diaphragm.

55. The amplifier assembly of clause 54, wherein the sensor is a Hall sensor.

56. The amplifier assembly of any of clauses 54 to 55, wherein the sensor comprises: a first magnet integrated into the proximal nose; a second magnet integrated into the distal waveguide at a specified distance from the first magnet; and an electrical probe located in a central region of the diaphragm.

57. The amplifier assembly of clause 56, wherein the proximal nose comprises a first receptacle configured to hold the first magnet in a fixed position.

58. The amplifier assembly of any of the preceding clauses, wherein the distal waveguide comprises a second receptacle to hold the second magnet in a fixed position.

59. The amplifier assembly of clause 58, wherein the first and second receptacles comprise crush ribs.

60. The amplifier assembly of any of clauses 56 to 59, wherein the electrical probe is electrically connected to the electrical assembly.

61 . The amplifier assembly of any of the preceding clauses, further comprising a magnet integrated into a central region of the diaphragm.

62. The amplifier assembly of any of the preceding clauses, further comprising: a housing, wherein the proximal nose, the distal waveguide and the diaphragm are present within the housing.

63. The amplifier assembly of clause 62, wherein the housing comprises one or more snap fit shells configured to substantially enclose the proximal nose, the distal waveguide and the diaphragm.

64. The amplifier assembly of any of clauses 61 to 63, wherein the housing comprises one or more flexible arms for interfacing with a handle assembly. 65. The amplifier assembly of clause 64, wherein the one or more flexible arms are configured to hold a proximal interface of the proximal nose in place relative to a handle assembly.

66. The amplifier assembly of any of clauses 64 to 65, wherein the one or more flexible arms are configured to provide tactile feedback for interfacing with a handle assembly.

67. The amplifier assembly of any of clauses 62 to 66, wherein the housing comprises one or more grooved sections configured for manually gripping the amplifier assembly.

68. A handle assembly for controllably transmitting energy, the assembly comprising: a coupler assembly operably connected to an energy source; a manifold, operably connected to the energy source through the coupler assembly and configured to controllably transmit energy to a distal interface; and the distal interface, operably connected to an output of the manifold and configured to transmit energy received from the manifold.

69. The handle assembly of clause 68, wherein the manifold comprises an oscillator operably connected to the energy source.

70. The handle assembly of clause 69, wherein the oscillator is configured to transmit energy through the manifold in a first position and to exhaust energy in a second position.

71 . The handle assembly of any of clauses 69 to 70, wherein the oscillator is a solenoid.

72. The handle assembly of any of clauses 68 to 71 , wherein the coupler assembly comprises input and exhaust couplers, wherein the input coupler is operably connected to an energy source and the exhaust coupler is configured to exhaust energy from the energy source.

73. The handle assembly of any of clauses 68 to 72, wherein the coupler assembly comprises tubing.

74. The handle assembly of clause 73, wherein the coupler assembly comprises input and exhaust tubing. 75. The handle assembly of clause 74, wherein the input tubing is operably connected to an energy source and the exhaust tubing is configured to exhaust energy from the energy source.

76. The handle assembly of any of clauses 68 to 75, wherein the manifold is operably connected to the energy source through an input coupler of the coupler assembly.

77. The handle assembly of any of clauses 68 to 76, further comprising an electrical assembly electrically connected to aspects of the manifold.

78. The handle assembly of clause 77, wherein the electrical assembly is configured to control the oscillator.

79. The handle assembly of clause 78, wherein the electrical assembly is configured to move the oscillator from a first position to a second position.

80. The handle assembly of any of clauses 77 to 79, wherein the electrical assembly is configured to interface with an external component.

81 . The handle assembly of any of clauses 77 to 80, wherein the electrical assembly is configured to receive input from an external component.

82. The handle assembly of any of clauses 77 to 81 , wherein the electrical assembly is electrically connected to a plurality of pin connectors.

83. The handle assembly of any of clauses 68 to 82, wherein the handle is configured to be held by an operator.

84. The handle assembly of clause 83, wherein the handle is configured to be held by an operator during use.

85. The handle assembly of any of clauses 68 to 84, wherein the handle weighs between 0.5 lbs. and 2.5 lbs.

86. The handle assembly of any of clauses 68 to 85, wherein the handle has a circumference of between 1 .5 in and 5.0 in.

87. The handle assembly of any of clauses 68 to 86, wherein the handle has a length of between 4.0 in and 8.0 in.

88. The handle assembly of any of clauses 68 to 87, wherein the handle comprises one or more tactile features. 89. The handle assembly of clause 88, wherein the tactile features comprise groves or indentations.

90. The handle assembly of any of clauses 68 to 89, further comprising a housing, wherein the manifold is present in the housing.

91 . The handle assembly of any of clauses 68 to 90, further comprising operator controls.

92. The handle assembly of clause 91 , wherein operator controls comprise a button.

93. The handle assembly of any of clauses 91 to 92, wherein the operator controls are configured to activate the oscillator.

94. The handle assembly of any of clauses 91 to 93, wherein operator controls comprise an output element.

95. The handle assembly of clause 94, wherein the output element indicates handle state.

96. The handle assembly of any of clauses 94 to 95, wherein the output element comprises one or more lights.

97. The handle assembly of any of clauses 94 to 96, wherein the output element is integrated into the button.

98. The handle assembly of any of clauses 68 to 97, configured to perform a system self-check.

99. The handle assembly of clause 98, wherein the system self-check is performed prior to activating the oscillator.

100. The handle assembly of any of clauses 98 to 99, wherein the system selfcheck detects leaks from the energy source.

101 . The handle assembly of any of clauses 98 to 100, wherein the system self-check detects leaks from the energy source in one or more external components to which the handle is operably connected.

102. The handle assembly of any of clauses 98 to 101 , wherein the system self-check evaluates whether an amplifier assembly according to any of clauses 1 to 67 is operably connected to the handle assembly. 103. The handle assembly of any of clauses 98 to 102, wherein the system self-check evaluates whether an amplifier assembly according to any of clauses 1 to 67 operably connected to the handle assembly functions as specified.

104. The handle assembly of any of clauses 98 to 103, wherein the system self-check evaluates whether an amplifier assembly according to any of clauses 1 to 67 functions as specified.

105. The handle assembly of any of clauses 98 to 104, wherein the system self-check evaluates whether a diaphragm of an amplifier assembly according to any of clauses 1 to 67 is displaced in connection with transmitting energy from the handle assembly to the amplifier assembly.

106. The handle assembly of clause 105, wherein the diaphragm is displaced a specified amount.

107. The handle assembly of any of clauses 68 to 106, wherein the distal interface comprises one or more alignment features.

108. The handle assembly of clause 107, wherein the alignment features comprise a keyed protrusion.

109. The handle assembly of any of clauses 68 to 108, wherein the distal interface is configured to operably interface with an external component.

1 10. The handle assembly of any of clauses 68 to 109, configured to operably interface with an amplifier assembly of any of clauses 1 to 67.

1 1 1. The handle assembly of any of clauses 68 to 110, wherein the handle assembly comprises one or more aspects configured to operably interface with an amplifier assembly of any of clauses 1 to 67.

1 12. The handle assembly of any of clauses 68 to 111 , wherein the handle assembly comprises a shape configured to releasably associate with an amplifier assembly of any of clauses 1 to 67.

1 13. The handle assembly of any of clauses 68 to 112, wherein the handle assembly comprises one or more aspects configured to operably connect with an amplifier assembly of any of clauses 1 to 67. 1 14. The handle assembly of any of clauses 68 to 113, wherein the handle assembly comprises a fluidic connection with an amplifier assembly of any of clauses 1 to 67.

1 15. The handle assembly of any of clauses 68 to 114, wherein the handle assembly comprises an electrical connection with an amplifier assembly of any of clauses 1 to 67.

1 16. The handle assembly of any of clauses 68 to 115, wherein the handle assembly comprises an interlock.

1 17. The handle assembly of clause 116, wherein the interlock is configured to disable transmission of energy in a case where the handle assembly cannot detect an amplifier assembly.

1 18. The handle assembly of any of clauses 1 16 to 117, wherein the interlock is configured to ensure an amplifier is operably connected to the handle assembly.

1 19. The handle assembly of any of clauses 1 16 to 118, wherein the interlock is configured to allow the handle assembly to transmit energy to an amplifier assembly in a case where the amplifier assembly is operably connected to the handle assembly.

120. The handle assembly of any of clauses 1 16 to 119, wherein the interlock is configured to prevent the handle assembly from transmitting energy to an amplifier assembly in a case where the amplifier assembly is not operably connected to the handle assembly.

121 . The handle assembly of any of clauses 68 to 120, wherein the distal interface is configured to operably interface with the proximal nose of the amplifier assembly.

122. The handle assembly of any of clauses 68 to 121 , wherein an alignment feature of the distal interface is configured to interface with a corresponding alignment feature of the proximal nose of the amplifier assembly.

123. The handle assembly of clause 122, wherein the alignment feature of the proximal nose of the amplifier assembly comprises a keyed face.

124. The handle assembly of any of clauses 68 to 123, wherein an electrical assembly of the handle assembly is configured to electrically connect to an electrical assembly of the amplifier assembly. 125. The handle assembly of clause 124, wherein the electrical assembly of the handle assembly comprises a plurality of electrical connectors.

126. The handle assembly of clause 125, wherein the electrical connectors comprise a plurality of pins.

127. The handle assembly of clause 126, wherein the electrical assembly of the handle assembly comprises between 2 and 25 pins.

128. The handle assembly of any of clauses 126 to 127, wherein the plurality of pins electrically connect to a plurality of plates of the electrical assembly of the amplifier assembly.

129. The handle assembly of any of clauses 126 to 128, wherein the plurality of pins are arranged on the handle assembly.

130. The handle assembly of any of clauses 126 to 129, wherein the plurality of pins are configured in a V-shaped arrangement.

131 . The handle assembly of clause 130, wherein a pin at the apex of the V- shaped plurality of pins is electrically connected to ground.

132. The handle assembly of any of clauses 128 to 131 , wherein the plurality of pins and the plurality of plates are arranged such that an electrical connection to ground is initially made upon operably connecting the amplifier assembly to the handle assembly.

133. The handle assembly of any of clauses 128 to 132, wherein the plurality of pins and the plurality of plates are arranged such that an electrical connection to ground is made prior to making other electrical connections upon operably connecting the amplifier assembly to the handle assembly.

134. The handle assembly of any of clauses 128 to 133, wherein the plurality of pins and the plurality of plates are arranged such that an electrical connection to ground is the last electrical connection to be disconnected when disconnecting the amplifier assembly from the handle assembly.

135. The handle assembly of any of clauses 128 to 134, wherein the plurality of pins and the plurality of plates are arranged such that an electrical connection to ground is disconnected subsequent to disconnecting other electrical connections when disconnecting the amplifier assembly from the handle assembly. 136. A system for imparting pulsatile energy, the system comprising: an amplifier assembly of any of clauses 1 to 67; and a handle assembly of any of clauses 68 to 135.

137. The system of clause 136, further comprising: a console assembly comprising an energy source operably connected to the handle assembly.

138. The system of clause 137, wherein the console assembly further comprises a regulator.

139. The system of any of clauses 137 to 138, wherein the energy source of the console assembly is a voltage potential or an electromagnetic potential or a pressure potential.

140. The system of any of clauses 137 to 139, wherein the console assembly comprises a regulator configured to regulate a first energy from the energy source to a second energy.

141 . The system of clause 140, wherein the regulator is an active regulator configured to be controlled by an electrical signal.

142. The system of clause 141 , wherein the regulator is a passive regulator configured to be preset to a specific output.

143. The system of any of clauses 137 to 142, wherein the console assembly further comprises a controller configured to: receive input from at least one of the console assembly, the handle assembly and the amplifier assembly, and adjust a configuration of the console assembly based at least in part on the input received.

144. The system of clause 143, wherein the controller is further configured to receive input from a source that is external to the system.

145. The system of any of clauses 143 to 144, wherein the controller is configured to receive input from at least one of: results of an electrocardiogram, an intravascular pressure monitor, a blood volume monitor or an imaging system. 146. The system of any of clauses 143 to 145, wherein the console assembly is a first console assembly, and the system comprises a plurality of operably connected console assemblies.

147. A method for imparting pulsatile energy to a tissue, the method comprising: deploying a pulsatile balloon catheter system according to any of clauses 136 to 146 so that a tissue-engaging element operably connected to the system is adjacent to tissue; and engaging the system in a manner that imparts energy to the tissue.

148. The method of clause 147, wherein the tissue-engaging element comprises a distal balloon.

149. The method of any of clauses 147 to 148, wherein the tissue-engaging element comprises a heart-tissue-conforming element.

150. The method of any of clauses 147 to 149, wherein the tissue-engaging element is operably connected to an output of the distal waveguide of the amplifier assembly of the system.

151 . The method according to any of clauses 147 to 150, wherein the method is a method of performing dynamic balloon angioplasty.

152. The method according to any of clauses 147 to 151 , wherein the method is a method of assessing vessel compliance.

153. A kit comprising an amplifier assembly of any of clauses 1 to 68.

154. The kit according to clause 153, further comprising a handle assembly of any of clauses 68 to 135.

155. The kit according to any of clauses 153 to 154, further comprising a console assembly of any of clauses 137 to 146.

156. The kit according to any of clauses 153 to 155, wherein one or more components of the kit are re-usable.

157. The kit according to clause 156, wherein the handle assembly is reusable.

158. The kit according to any of clauses 153 to 157, wherein one or more components of the kit are sterile. 159. The kit according to any of clauses 153 to 158, further comprising packaging.

[0299] In at least some of the previously described embodiments, one or more elements used in an embodiment can interchangeably be used in another embodiment unless such a replacement is not technically feasible. It will be appreciated by those skilled in the art that various other omissions, additions and modifications may be made to the methods and structures described above without departing from the scope of the claimed subject matter. All such modifications and changes are intended to fall within the scope of the subject matter, as defined by the appended claims.

[0300] It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “ a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.”

[0301] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0302] As will be understood by one skilled in the art, for any and all purposes, such as in terms of providing a written description, all ranges disclosed herein also encompass any and all possible sub-ranges and combinations of sub-ranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a nonlimiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1 -3 articles refers to groups having 1 , 2, or 3 articles. Similarly, a group having 1 -5 articles refers to groups having 1 , 2, 3, 4, or 5 articles, and so forth.

[0303] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.

[0304] Accordingly, the preceding merely illustrates the principles of the invention. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors to furthering the art and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and embodiments of the invention as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims.

[0305] The scope of the present invention, therefore, is not intended to be limited to the exemplary embodiments shown and described herein. Rather, the scope and spirit of present invention is embodied by the appended claims. In the claims, 35 U.S.C. §1 12(f) or 35 U.S.C. §1 12(6) is expressly defined as being invoked for a limitation in the claim only when the exact phrase “means for” or the exact phrase “step for” is recited at the beginning of such limitation in the claim; if such exact phrase is not used in a limitation in the claim, then 35 U.S.C. § 112 (f) or 35 U.S.C. §1 12(6) is not invoked.

Claims

WHAT IS CLAIMED IS:

1 . An amplifier assembly, the assembly comprising: a proximal nose, comprising a distal face; a distal waveguide, comprising a proximal face; and a diaphragm sealed between the proximal nose and the distal waveguide separating a proximal chamber from a distal chamber, wherein the diaphragm is configured to: translate between the distal face of the proximal nose and proximal face of the distal waveguide, conform to the distal face of the proximal nose in a proximal position of the diaphragm, and conform to the proximal face of the distal waveguide in a distal position of the diaphragm.

2. The amplifier assembly according to claim 1 , wherein the diaphragm comprises a shape that conforms to the distal face of the proximal nose in a proximal position of the diaphragm and conforms to the proximal face of the distal waveguide in a distal position of the diaphragm.

3. The amplifier assembly according to any of the preceding claims, wherein the diaphragm comprises one or more of: folds, pleats and pleated bellows.

4. The amplifier assembly according to any of the preceding claims, wherein the distal waveguide is configured to produce smooth fluid flow from the diaphragm to a distal region of the distal waveguide.

5. The amplifier assembly according to any of the preceding claims, wherein the distal waveguide comprises a shape configured reduce turbulence of fluid flow from the diaphragm to a distal region of the distal waveguide.

6. The amplifier assembly according to any of the preceding claims, wherein the distal waveguide comprises a funnel-like geometry.

7. The amplifier assembly according to any of the preceding claims, wherein the proximal nose comprises a proximal interface located at a proximal region of the proximal nose.

8. The amplifier assembly according to claim 7, wherein the proximal interface comprises a high-pressure connector.

9. The amplifier assembly according to any of the preceding claims, further comprising an electrical assembly integrated into one or more of the proximal nose, the distal waveguide and the diaphragm.

10. The amplifier assembly according to any of the preceding claims, further comprising a pressure sensor configured to sense fluid pressure within the distal waveguide.

1 1 . The amplifier assembly according to claim 10, wherein the pressure sensor is integrated into the distal waveguide.

12. The amplifier assembly according to any of the preceding claims, further comprising a sensor configured to sense to the position of the diaphragm.

13. The amplifier assembly according to claim 12, wherein the sensor is a Hall sensor.

14. The amplifier assembly according to any of the preceding claims, wherein the amplifier assembly further comprises a balloon catheter operably connected to the distal waveguide.

15. The amplifier assembly according to claim 14, where the amplifier assembly is operably connected to an energy source.

16. The amplifier assembly according to claim 15, wherein the energy source comprises a pulse generator.

17. A system comprising an energy source operably coupled to an amplifier assembly according to claim 14.

18. The system according to claim 17, wherein the energy source comprises a pulse generator.

19. The system according to claim 18, wherein the pulse generator comprises a console and a handle.

20. A method comprising operably connecting an amplifier assembly according to claim 14 to an energy source.

21 . The method according to claim 17, wherein the energy source comprises a pulse generator.

22. The method according to any of claims 17 to 18, wherein the method further comprises positioning a balloon of the balloon catheter adjacent to a tissue.

23. The method according to claim 19, wherein the method further comprises imparting energy to the tissue.