Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
  • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
  • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
  • A61B5/6852—Catheters
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
  • A61B5/02007—Evaluating blood vessel condition, e.g. elasticity, compliance
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
  • A61B5/02028—Determining haemodynamic parameters not otherwise provided for, e.g. cardiac contractility or left ventricular ejection fraction
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
  • A61B5/024—Measuring pulse rate or heart rate
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/03—Measuring fluid pressure within the body other than blood pressure, e.g. cerebral pressure ; Measuring pressure in body tissues or organs
  • A61B5/032—Spinal fluid pressure
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/48—Other medical applications
  • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
  • A61B5/4839—Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B2560/00—Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
  • A61B2560/02—Operational features
  • A61B2560/0223—Operational features of calibration, e.g. protocols for calibrating sensors
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M25/00—Catheters; Hollow probes
  • A61M2025/0001—Catheters; Hollow probes for pressure measurement
  • A61M2025/0002—Catheters; Hollow probes for pressure measurement with a pressure sensor at the distal end
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M25/00—Catheters; Hollow probes
  • A61M25/01—Introducing, guiding, advancing, emplacing or holding catheters
  • A61M25/0105—Steering means as part of the catheter or advancing means; Markers for positioning
  • A61M2025/0166—Sensors, electrodes or the like for guiding the catheter to a target zone, e.g. image guided or magnetically guided
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M25/00—Catheters; Hollow probes
  • A61M25/0067—Catheters; Hollow probes characterised by the distal end, e.g. tips
  • A61M25/0082—Catheter tip comprising a tool

Definitions

• the present invention relates to systems and methods for computational medical devices able to be used in conjunction with dynamic body systems.
• Such systems and methods provide for a fuller characterization between interrelated body systems, such as the cardiovascular system and cerebrospinal system, for example. Through these better understandings of interrelationships between dynamic systems, more successful diagnostic and therapeutic measures may be employed.
• the cerebrospinal fluid flow has two components. A bulk flow from the production and absorption of cerebrospinal fluid and a pulsatile/oscillatory flow from influence of the cardiac cycle on the bulk flow. Also, there are respiratory and body positional influences on the cerebrospinal fluid flow.
• a computational catheter device including at least one lumen, at least one pressure sensor, at least one external sensor, a signal modeler, and a signal analyzer is provided.
• the pressure sensor generates a pressure signal for a dynamic body system, whereas the external sensor determines the fundamental frequency caused by cardiovascular pulsation.
• the signal modeler uses catheter location and the fundamental frequency to generate a predicted signal. This predicted signal may be compared to the actual pressure signal by the signal analyzer to generate a calibration.
• This calibration may include any of a measure of perivascular state, a waveform output which causes standing waves within the dynamic body system, a boundary condition for safe operations, and an indication of abnormal physiology for assistance in catheter navigation.
• the catheter device may also include an actuator connected to a computational circuit. The computational circuit utilizes the calibration and the actuator to achieve homeostasis by fluxing fluids.
• the catheter system also includes a microsurgical tool port, a multi-sensor array, at least one fluid pathways coupled to the lumen, a collapsible member, and/or a transducer.
• the multi-sensor array may include any of a flow meter, chemical sensor, antibody sensor, electrical resistance sensor, spectrographic sensor, and differential pressure sensor.
• the transducer may transmit either of ultrasound energy or electromagnetic energy.
• Figure 1 is an example illustration of computational catheter medical device, in accordance with some embodiments.
• Figures 2A and 2B are example diagrams illustrating signal calibration and compliance, in accordance with some embodiments.
• Figure 3 is an example diagram illustrating means for defining safe catheter navigation in the setting of an unstable plaque, in accordance with some embodiments
• Figures 4A and 4B are example illustrations of computational analysis of the arterial waveform versus cerebral spinal fluid waveform and offset, in accordance with some embodiments;
• Figure 5 is an example illustration of the perivascular space at different points during the vascular cycle, in accordance with some embodiments;
• Figure 6 is a logical block diagram for the operation of an example computational catheter medical device, in accordance with some embodiments.
• Figure 7 is an example flowchart for the process of employing the computational medical device, in accordance with some embodiments.
• the present invention relates to a novel and improved medical device that has application in computational analysis of body systems.
• a catheter device capable of sensing pressure variance within the body in order to characterize fluid dynamics of the system.
• many body systems are non-static and may be influenced by other body systems.
• the cardiovascular system produces pulsatile fluid pressure changes with far reaching impact into other systems, such as the cerebrospinal system and respiratory system. Every heart beat sends a fundamental frequency through the cardiovascular system. The interaction of the perfusion with other systems and diseases adds overtones.
• such computational medical devices may enable a number of more effective therapies, including without limitation:
• embodiments of the computational medical device are structured such that a catheter enters a cavity or pathway in the body and allows real-time diagnostics and therapeutics.
• the computational medical device employs certain associated software.
• This software contains a computer model of the associated anatomy and physiology and allows probabilistic predictions of the current state of the body system based on input from a multisensory array. The software then compares the actual recordings from the system to the predicted and can make interventions accordingly, such as alerting healthcare personnel or causing changes in actuator/micro-pump behavior to bring the system back into equilibrium.
• fluid and air filled cavities are subject to pulsatile and oscillatory waves. This can sometimes disrupt local drug delivery and surgical interventions.
• a computational medical device such as the one disclosed herein, may be able to analyze the oncoming signal, generate feedback for the waveform with micromotors thereby producing standing waves, which could facilitate local drug delivery or stable surgical interventions.
• navigating the catheter in standing wave conditions may reduce the work required for catheter advancement thereby reducing inflammation and vessel/conduit injury.
• Figure 1 is an example illustration of computational catheter medical device, shown generally at 100.
• the catheter device is illustrated by way of example, it is possible for systems to have alternate embodiments wherein the specific functionality of the illustrated catheter are decoupled from one another.
• the catheter and components in some embodiments may be on a micro- or nana- scale.
• the catheter 100 is illustrated here as including integrated microprocessors 112, it is entirely within the scope of this disclosure that such processing capabilities are instead embodied in an external computer device and may be coupled to the remainder of the catheter.
• a transducer section 102 is seen tipping the catheter. This transducer 102 may send and receive ultrasound,
• the catheter may also include one or more multisensory arrays 104.
• pressure sensor(s) including differential pressure and static pressure capabilities. Any pressure sensing technology that allows real-time analysis is acceptable for some embodiments: diaphragm, load sensor, etc.
• the pressure sensor(s) assesses changes in pressure and wave characteristics, and is analyzable with a computer for the power spectra. MEMS sensors, micro-manometers and/or load cells along the dura could detect sensitive pulsations and waveforms. The assessment of dynamic and static aspects of flow will facilitate the regulation of the bulk component and regulate the pulsatile components of the flow independently.
• these sensory arrays 104 may include chemical sensors, oxygen sensors, acoustic sensors, electromagnetic sensors, flow, capacitance and resistance sensors, optical/camera sensors, spectroscopy, antibody, laser Doppler, and/or any other sensory array useful for physiological diagnostic purposes.
• Flow sensors may include any of differential pressure, pitot tube, microcoriolis, magnetic, ultrasonic, variable area, vortex, target, thermal, or turbine sensors. While two sensor arrays 104 are illustrated, in some embodiments, only one, or more than two sensory arrays may be utilized.
• the catheter may also include one or more fluid pathways 108 for delivering and removing fluids from the body. These fluid pathways may all tie into a single lumen, thereby allowing for diffuse fluid transfers. Alternatively, the fluid pathways 108 may couple to two or more lumens (thereby enabling differing fluid flux rates at different locations of the catheter), and even simultaneous insertion and removal of fluids (thereby allowing for fluid exchange with minimal pressure or volume changes imposed upon the surrounding tissue). Note that while two fluid pathway ports 108 are illustrated, any number may be employed in the catheter as is desired.
• the catheter system may include micro-pumping actuators
• the computational circuitry 112 may be utilized to calibrate actuator 110 activities to ensure homeostasis is maintained in the patient.
• the actuator 110 may include one or more of motors, pumps, valves, microsurgical tools, and/or steering elements.
• the computational circuitry 112 may have embedded modeling system which may utilize models to generate predicted pressure signals in an intended body system, a signal analyzer capable of comparing the predicated signal vs. actual signals, feedback pathways that enable the system into homeostasis, and other algorithms for analysis and safe intervention. Models employed by the system may include variations on Marmorou and Czosnyka algorithms, for example.
• the catheter system may also include mechanical, chemical, antibody and cellular filters.
• the catheter system may include a wire interface or antennae that can collect information from external signals (such as an EKG).
• the heart pumping produces a fundamental frequency that is carried through other systems.
• This fundamental signal travels through the vascular system and is influenced by the length and stiffness of the anatomy, among other things, and can be influenced by the respiratory and body positional systems.
• This fundamental frequency is also transferred to the cerebrospinal pressure wave via the vascular pulsations of the brain.
• the coupling of the cardiovascular wave and cerebrospinal pressure wave is thought to drive fluid exchange from the substance of the brain and spinal cord, allowing removal of harmful metabolites.
• Monitoring this fundamental frequency with an oximeter, EKG, echocardiogram, etc., can provide a reference signal useful for identifying a derivative signal within noise, comparing the phase and offset of signals and timing various effectors/actuators as well as other diagnostic and therapeutic interventions.
• systems are all illustrated as being embodied upon a singular catheter device. While this may be a desired layout in some cases, it may be beneficial to have these systems physically decoupled.
• two catheters may be employed: one for sensory collection and the other for fluid pathways.
• the pumps and computational circuitry could likewise be external to the patient and coupled to the fluid pathway catheter and sensory catheter, respectively. Other permutations are likewise considered within the scope of this disclosure.
• the benefits of the catheter device 100 are that it enables real-time collection of sensory data and simultaneous computational analysis of the data in order to calibrate interventions within the individualized patient. These calibrations enable safe interventions without undue restrictions on operation. In particular, such a calibration step would be useful for interventions in system that are defined by a given compliance and outflow resistance over the arterial cycle, such as cardiovascular, respiratory and neurological systems, among others, along with a unique profile of the pathologies, such as areas of scarring or plaque-like depositions, which may be unstable. Interventions include drug delivery, cerebrospinal dialysis, hemodialysis, blood transfusions and some intravenous administrations. In the past, safety of interventions could only be ensured by taking a very conservative approach toward therapy.
• Figures 2A and 2B are example diagrams illustrating signal calibration and compliance, in accordance with some embodiments.
• Figure 2 A shows oscillatory work over time. Volume is illustrated at line 202, while pressure is illustrated at curve 208. Ascending cycles 204 and descending cycles 206 are also illustrated.
• the calibration analysis defines a hysteresis curve, with a descending leg 210 (impedance curve) and ascending leg 212 (outflow resistance curve), as seen at Figure 2B with underlying compliance curve 214 defining the safe zone 218 of intervention where max compliance curve and a danger zone 216. Interventions to increase compliance such as off cardiac cycle pressure or volume delivery are possible.
• Passive computational analysis of the heart's fundamental signal along with the overtones added by the anatomical system will provide a beat-to-beat resolution of the dynamic characteristics of a system.
• an external frequency oscillator may deliver a signal at a rate different than the heart and the response of the system can be collected and analyzed. This external signal may be an acoustic volley (e.g., infrasonic to ultrasonic) or electromagnetic (e.g., laser Doppler flowmetry) wave.
• the anatomical system is interrogated, with a known signal
• the transmitted signal may be at a higher frequency than the heart's fundamental frequency, thereby increasing the resolution of analysis.
• the pressure curve 208 defines a zone of maximal compliance 218 where safe interventions may take place. Therapeutic interventions may therefore take place at higher-than-normal equilibrium pressures, as long as the intervention remains within the targeted safe zone of 218.
• Analysis of the pressure response curve 208 will help define a danger zone 216, where small incremental changes in volume result in very large changes in pressure and system instability. The danger zone 216 could be avoided in therapeutic interventions. Real-time analysis and intermittent recalibration can help keep any diagnostic and therapeutic interventions along the safe zone and avoid the danger zone.
• Figure 3 is an example diagram illustrating means for defining safe catheter navigation in the setting of an unstable plaque, shown generally at 300. This is important because the rupture of atherosclerotic plaques leads to myocardial infarction. Complex plaque morphology and contents are associated with unstable angina. Plaque rupture and thrombus formation are dynamic processes. After rupture, reduction of coronary blood flow results from platelet aggregation, thrombosis and spasm.
• Procedural complications for percutaneous trans-luminal coronary angioplasty for unstable angina are higher than for stable angina and may result from iatrogenic plaque injury.
• a catheter itself represents a volume that is delivered to a distensible system governed by its compliance and outflow resistance. Analyzing the structure and flow characteristics of the system before, during and after intervention may be advantageous. Interrogation of the system with dynamical interventions such as catheter movements, fluid volume changes, acoustic and/or electromagnetic pulses may help define the system and comprise a calibration step defining a structural and flow profile unique to a patient. This calibration step prior to intervention may minimize untoward effects and provide a basis for continuous monitoring before, during and after a procedure.
• a vessel 302 is illustrated with the catheter 100 inserted into its luminal space. Upstream is an unstable plaque 304. Unmonitored and uncalibrated navigation and fluid delivery can dislodge the plaque leading to iatrogenic injury, as these interventions change the volume, pressure, flow and shear stresses of the system. A calibration algorithm may be utilized to guide safe intervention. A computational model can predict the anticipated waveform from fundamental heart frequency input. The vessel plaque can introduce harmonics in the signal which can be elucidated with power spectra analysis. The initial flow 306 through the vessel is very similar to the modeled pressure signal. Once the flow passes the plaque 304 the harmonics of the flow are altered thereby leading to an altered flow 308. This altered flow 308 may be compared to the expected signal to identify the plaque.
• the bounds of safe intervention can be assessed.
• One strategy would employ subtle manipulations of the volume with concurrent analysis of the response of the system by measuring the cardiac beat-to beat variations in pressure and/or flow Alternatively, an external signal faster the heart's fundamental frequency, such as a sonic (sonar) type wave or laser Doppler signal can be transmitted and received to complement the beat- to-beat analysis of waveform.
• Subtle changes in volume and response can occur with catheter translational oscillations and other stresses determined by rotational oscillations of the catheter. These vibrations can assist in determining the instability of a plaque or scar or assist with navigation along the tortuosity of small blood vessels.
• a catheter is a known volume, so entering the vessel will displace a volume of fluid. As such, outflow resistance may be assessed and coordinated fluid in/out flow can be achieved with the control system to maintain an equilibrium.
• Perivascular spaces of around 25 microns surround points of entry of arteries into the substance of the brain and spinal cord. This perivascular anatomy is thought to form a specialized lymphatic system which allows the efflux and processing of excess proteins and particles the interstitium. The perivascular spaces are not uniformly open at all times. Rather, the opening and closing of the perivascular space is thought to be due to arterial pulsations within the vessels, in effect gated by the cardiac and arterial cycles.
• the perivascular channels can become clogged with debris, leading to edema, microcyst formation, syrinxes and even untoward vascular events such as vasopasm, and other stroke and ischemia.
• perivascular spaces By analyzing the state of the perivascular spaces, it is possible to restrict pumping to when perivascular spaces are closed, which may be beneficial given that with the cardiac cycle, the opening of a large magnitude of perivascular spaces may affect sensitive measures of CSF outflow and also transiently changing the CSF compliance through the recruitment of additional volume of CSF pathways. Once the CSF is cleared of debris and back to equilibrium, pumping may be undertaken during the arterial cycle when the perivascular spaces are open to facilitate clearance of any remaining interstitial proteins and debris without fear of clogging the system.
• Beat-to- beat analysis of the response of the system could facilitate the calibration of the system, but continuous interrogation with another signal such as an acoustic pulse and/or laser Doppler flowmetry may provide even faster resolution and assessment of compliance and outflow resistance than beat-to-beat monitoring could. Such analysis could complement or replace beat-to-beat evaluation. Clearance of perivascular and microvascular debris could also be facilitated with ultrasonic energy
• FIGs 4 A and 4B are example illustrations of computational analysis of the arterial waveform versus cerebral spinal fluid (CSF) waveform and offset, in accordance with some embodiments.
• This relationship is important as the arterial phase gates the opening of perivascular spaces which allows clearance of interstitial toxins from the brain and spinal cord.
• CSF cerebral spinal fluid
• a pumping cycle would benefit from avoiding activity during the open perivascular phase as debris would be pushed deeper in the tissue causing inflammation and ischemia. Once the CSF is clear, the pumping cycle could resume during the open perivascular cycle to facilitate toxin removal.
• real-time CSF component analysis, arterial phase monitoring (which may be assessed via computer model or direct ultrasound or laser Doppler analysis via the catheter system), CSF wave, arterial / CSF offset and pump cycle all need to be coordinated with careful computational circuitry which is necessary for safe
• Drug delivery in the CSF may operate under similar analysis and action.
• Drug delivery may include any type of drug therapy desired, including insulin like growth factors, anti-inflammatory medications and the like.
• FIG. 4B is an example illustration of the perivascular space 512 at different points during the vascular cycle.
• the contracted vessel 510 is seen in drawing A as having an open perivascular space 512.
• Tissue surrounds 514 the perivascular space.
• drawing B the vessel is expanded 516 and the perivascular space is closed 518.
• FIG. 6 is a logical block diagram for the operation of an example computational catheter medical device.
• the heart 602 provides a fundamental frequency which can be assessed with an external probe 604 such as oximeter, EKG, echocardiogram, etc., which is fed into a computer i/o 606 via wire or wirelessly.
• the computer i/o 606 sends the input to an anatomical/pathological modeler 608 and transformational module 610 which transforms the input (e.g., via a transfer function) to an expected signal 612 based on the computer model of the intended physiological system, which can take into account a number of variables supplied also by internal multisensory probes.
• the actual signal 616 is measured via sensor(s) 618, and is compared to the expected signal 612 via a spectral analyzer 614. If equivalent, interventions can continue according to the calibration step described previously. If different, medical personnel are notified and/or the device autonomously seeks to restore homeostasis via algorithms and actuators under real-time analysis.
• Algorithm driven actuators 620 change the volume of a dynamic fluid system 624 by fluid delivery/removal or device movement to ensure homeostasis.
• the external fundamental frequency oscillator 622 may deliver a signal at a rate different than heart 602 and the response of the system collected and analyzed.
• This external signal may be an acoustic volley (e.g., infrasonic to ultrasonic) or electromagnetic (e.g., laser Doppler flowmetry) wave.
• the anatomical system of interest could be interrogated, whereby a known signal (comprised of an individual frequency, sweeping frequencies or band-limited noise) is transmitted and the resulting reflected signal is collected and analyzed.
• the transmitted signal of the external fundamental frequency oscillator 622 may be at a higher frequency than the heart's fundamental frequency 602, thereby increasing the resolution of analysis of the computer I/O.
• FIG. 7 is an example flowchart for the process of employing the computational medical device, in accordance with some embodiments.
• the endogenous heart frequency or external frequency generated by an oscillator
• the heart frequency is used to model expected signals in the intended physiological system (at 704).
• the actual signal from the system is measured (at 706), and the actual signal is compared to the actual signal (at 710).
• a tolerance may be based upon intended physiology. For example, in highly sensitive body systems (such as the CNS), the tolerance for signal discrepancy may be set very low, whereas for pulmonary systems a higher tolerance may be acceptable.
• the system may start or continue interventions in accordance to calibrations (at 716). The system then continues monitoring the heart frequency and actual signals to ensure continued compliance.
• the system may notify medical personnel (at 712) and actively utilize algorithms to drive actuators to restore homeostasis in the patient (at 714). Once homeostasis has been achieved, the system continues monitoring the heart frequency and actual signals to ensure continued compliance.
• the present invention provides systems and methods for a computational medical device which enables calibration of diagnostics and therapies to the pressure effects of different body systems than the one being treated.
• Such systems and methods may allow for enhanced therapy by more accurately defining safe operational parameters, improve catheter navigation, and determine best pumping schemas when changing fluid volumes.

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• 2013
  • 2013-04-19 WO PCT/US2013/037491 patent/WO2013159072A1/fr not_active Ceased

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