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WO2024167522A1 - Système de détection d'anomalie valvulaire et structurale non invasive basé sur des aberrations d'écoulement - Google Patents

Système de détection d'anomalie valvulaire et structurale non invasive basé sur des aberrations d'écoulement Download PDF

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WO2024167522A1
WO2024167522A1 PCT/US2023/062068 US2023062068W WO2024167522A1 WO 2024167522 A1 WO2024167522 A1 WO 2024167522A1 US 2023062068 W US2023062068 W US 2023062068W WO 2024167522 A1 WO2024167522 A1 WO 2024167522A1
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left ventricular
outflow tract
ventricular outflow
measurement
pulse
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Mark Ries Robinson
Elena A. ALLEN
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Medici Technologies LLC
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Medici Technologies LLC
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Priority to US18/618,730 priority patent/US20240268694A1/en
Publication of WO2024167522A1 publication Critical patent/WO2024167522A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus, e.g. for MRI, optical tomography or impedance tomography apparatus; Arrangements of imaging apparatus in a room
    • A61B5/0035—Features or image-related aspects of imaging apparatus, e.g. for MRI, optical tomography or impedance tomography apparatus; Arrangements of imaging apparatus in a room adapted for acquisition of images from more than one imaging mode, e.g. combining MRI and optical tomography
    • 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
    • A61B5/02416—Measuring pulse rate or heart rate using photoplethysmograph signals, e.g. generated by infrared radiation
    • 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
    • A61B5/026—Measuring blood flow
    • A61B5/0261—Measuring blood flow using optical means, e.g. infrared light
    • 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
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6814—Head
    • A61B5/6815—Ear
    • A61B5/6817—Ear canal
    • 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
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6814—Head
    • A61B5/6821—Eye
    • 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
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6823—Trunk, e.g., chest, back, abdomen, hip
    • 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
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6825—Hand
    • A61B5/6826—Finger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7271—Specific aspects of physiological measurement analysis
    • A61B5/7282—Event detection, e.g. detecting unique waveforms indicative of a medical condition
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B27/00—Optical systems or apparatus not provided for by any of the groups G02B1/00 - G02B26/00, G02B30/00
    • G02B27/48—Laser speckle optics

Definitions

  • the present invention relates to the noninvasive determination of structural and valvular abnormalities in the left ventricular outflow tract by analysis of noninvasive optical pulse plethysmogram.
  • the noninvasive system enables testing in the clinic and does not require expensive direct assessment of blood flow characteristics at the location of the abnormality.
  • FIG. 1 is an illustration of aortic stenosis progression and flow impact, and illustrates flow compromise as the valvular area becomes restricted.
  • the narrowing requires increased pressure within the heart to pump blood across a smaller opening. This is similar to attaching smaller and smaller nozzles to the end of a garden hose (bottom row of the figure). The narrowing of the nozzle slows the forward flow of water, creates a jet of flow with higher velocities, and results in pressure buildup within the garden hose.
  • Aortic stenosis is the most common of type of left ventricular outflow tract obstruction in developed countries.
  • the typical course of AS involves a long asymptomatic period— many patients with severe AS are asymptomatic. Once symptoms begin, mortality increases. Without surgery, 40% to 50% of patients with classic symptoms die within 1 year.
  • FIG. 2 reproduced from the paper by Carabello et al., graphically illustrates the consequences of aortic stenosis with significant mortality after the development of symptoms. The table illustrated the ability of the heart to maintain cardiac output even in the presence of diminished valvular area. (Carabello, Blase A., and Walter J. Paulus.
  • LVOT Left ventricular outflow tract
  • LVOT abnormalities are conditions that affect the structure or function of the left ventricular outflow tract, which is the part of the heart that carries blood from the left ventricle (the heart's main pumping chamber) to the rest of the body. These abnormalities can range from mild to severe and significantly impact heart function and overall health.
  • Stenosis This is a narrowing of the left ventricular outflow tract, which can reduce the amount of blood that is able to flow out of the left ventricle and into the body. Stenosis can be caused by a variety of factors, including scar tissue, plaque buildup, or congenital defects.
  • Hypertrophy This is an abnormal thickening of the walls of the left ventricle, which can lead to an enlarged left ventricular outflow tract. Hypertrophy can be caused by high blood pressure, heart disease, or other conditions.
  • Aneurysm This is a bulge or ballooning in the wall of the left ventricle, which can cause the left ventricular outflow tract to become enlarged and weakened. A variety of factors, including coronary artery disease, high blood pressure, and genetics, can cause aneurysms.
  • Coarctation This is a condition in which the left ventricular outflow tract is constricted or narrowed, which can reduce blood flow to the body. A variety of factors, including congenital defects and scar tissue can cause coarctation.
  • Valvular stenosis is the most common type and constitutes approximately 65 to 75% of cases, whereas subvalvular and supravalvular stenosis constitutes approximately 15% to 20% and 5% to 10% of cases, respectively.
  • HCM hypertrophic cardiomyopathy
  • Aortic stenosis is a common disease that usually affects older patients. Aortic stenosis is a narrowing of the aortic valve opening. Aortic stenosis restricts the blood flow from the left ventricle to the aorta and may also affect the pressure in the left atrium. Although some people have aortic stenosis because of a congenital heart defect called a bicuspid aortic valve, this condition more commonly develops during aging as calcium or scarring damages the valve and restricts the amount of blood flowing through the left ventricular outflow tract.
  • supravalvular left ventricular outflow tract obstruction is a narrowing (stenosis) of the large blood vessel that carries blood from the heart to the rest of the body (the aorta).
  • the condition is described as supravalvular because the section of the aorta that is narrowed is located just above the valve that connects the aorta with the heart (the aortic valve).
  • Degenerative valvular heart disease includes aortic valve stenosis, mitral regurgitation, aortic regurgitation, and mitral stenosis.
  • the diagnosis and evaluation of valvular disease is challenging due to various pitfalls. These include discrepancies between the severity of valve dysfunction and patient symptoms.
  • a number of confounding factors and technical issues affect the assessment, including the presence of concurrent conditions such as uncontrolled hypertension, rapid atrial fibrillation, left ventricular dysfunction, and other valvular dysfunctions.
  • auscultation in which a healthcare provider listens to the heart with a stethoscope to determine if any abnormal sounds may indicate aortic stenosis.
  • auscultation there are several limitations to the use of auscultation for this purpose.
  • One limitation is that the accuracy of auscultation for diagnosing aortic stenosis can vary depending on the individual's body habitus and the presence of other conditions that may affect the sounds heard through the stethoscope. For example, obesity or the presence of lung disease can make it more difficult to interpret the sounds heard during auscultation accurately.
  • auscultation can be a useful tool for diagnosing aortic stenosis, it should be combined with other tests, such as echocardiography or cardiac catheterization to ensure an accurate diagnosis.
  • Echocardiography or ultrasound, is the most common test used to diagnose aortic stenosis. This test uses sound waves to create a visual image of the heart and can provide detailed information about the size and function of the aortic valve. However, the accuracy of echocardiography may be limited in cases where the patient has poor acoustic windows or when there are calcifications or other abnormalities in the aortic valve that can affect the accuracy of the image.
  • Magnetic resonance imaging is another test that can be used to diagnose aortic stenosis. This test uses a powerful magnetic field and radio waves to create detailed images of the heart and surrounding structures. While MRI is generally very accurate and provides detailed images, it is not always feasible for patients with certain medical implants or conditions that may be affected by the magnetic field.
  • Cardiac catheterization also known as angiography
  • angiography is a more invasive test that involves inserting a small tube (catheter) into a blood vessel and injecting a contrast agent to visualize the blood vessels and heart.
  • This test can provide detailed information about the anatomy of the aortic valve and the blood flow through it. However, it does involve some risks and is generally reserved for cases where other tests are inconclusive or when treatment is being planned.
  • Computed tomography is another test that can be used to diagnose aortic stenosis. This test uses x- rays to create detailed images of the heart and surrounding structures. While CT is generally very accurate and provides detailed images, it does expose the patient to radiation and may not be suitable for patients who are pregnant or have certain medical conditions. A comparison of the diagnostic modalities is shown in FIG. 3 and includes catheterization, CT, and MRI. [26] Due to the difficulty of detecting left ventricular outflow tract obstructions via clinical exam and the cost associated with ultrasound determination, there is a need for a simple screening test that could be administered in the patient's home or the outpatient clinic.
  • Embodiments of the present invention provide an apparatus for determining the presence of a structural or valvular heart abnormality in the left ventricular outflow tract of a patient, comprising: a peripherally attached noninvasive speckle sensor system comprising one or more optical sensors configured to measure an optical pulse plethysmogram sensitive to both the systolic pulse wave and reflected pulse waves; a sensor control system configured to operate the noninvasive speckle sensor system during a measurement period comprising at least one cardiac cycle to produce a measurement signal during the systolic and diastolic phases of the at least one cardiac cycle; a left ventricular outflow tract assessment system comprising a programmed data processor and memory, wherein the programmed data processor is programmed to implement a mapping function between the measurement signal and the presence or absence of a left ventricular outflow tract anomaly; a left ventricular outflow tract reporting system configured to report the presence or absence of a left ventricular outflow tract abnormality.
  • a peripherally attached noninvasive speckle sensor system comprising one or more
  • the programmed data processor is programmed to use morphologic waveform analysis to create a prediction model, and to use the prediction model to determine the presence or absence of a left ventricular tract anomaly. In some embodiments, the programmed data processor is programmed to use a matching model to determine the presence or absence of a left ventricular tract anomaly. In some embodiments, the programmed data processor is programmed to use a set of parameters that define a mapping function between the measurement signal and the left ventricular outflow tract abnormality. In some embodiments, the programmed data processor is programmed to use a set of parameters defining a mapping function between the measured signals and the area of the aortic valve and to determine the severity of aortic stenosis.
  • the sensor control system is configured to operate the sensor system during a measurement period comprising a period during which the patient performs one or more volitional maneuvers, and wherein the left ventricular outflow tract assessment system is configured to determine the presence or absence of a left ventricular outflow tract anomaly based the measurement signal. In some embodiments, the left ventricular outflow tract assessment system is configured to determine the presence or absence of a left ventricular outflow tract anomaly based on morphologic waveform analysis of the measurement signal.
  • Embodiments of the present invention provide an apparatus for determining the presence of a left ventricular outflow tract abnormality of a patient, comprising: an optical measurement system comprising (I) one or more optical emitters configured to emit light toward a measurement region of the user and (II) one or more detectors configured such that light reaches the detectors from the one or more emitters after the light from the emitters has interacted with the measurement region; a sensor control system configured to operate the sensor system at a first set of operational parameters to detect changes in blood flow or blood volume to produce a first measurement signal that is sensitive to the systolic pulse wave and reflected pulse waves during at least one cardiac cycle; a left ventricular outflow tract assessment system comprising a programmed data processor and memory, wherein the programmed data processor is programmed to implement a mapping function between the first measurement signal and the presence or absence of a left ventricular outflow tract abnormality; a left ventricular outflow tract reporting system configured to report the presence or absence of a left ventricular outflow tract abnormality.
  • the noninvasive flow sensor system is a speckle plethysmograph. In some embodiments, the noninvasive flow sensor system is a photo plethysmograph. In some embodiments, the noninvasive flow sensor system comprises a speckle and a photo plethysmograph. In some embodiments, the left ventricular outflow tract assessment is configured to use morphologic waveform analysis to create a prediction model, and to use the prediction model to determine the presence or absence of a left ventricular tract anomaly. In some embodiments, the left ventricular outflow tract assessment is configured to use a matching model to determine the presence or absence of a left ventricular tract anomaly.
  • Embodiments of the present invention provide a method for determining the presence of structural or valvular heart abnormalities in the left ventricular outflow tract of a patient, comprising: providing a noninvasive optical sensor system configured to detect changes in blood volume or blood flow in a measurement region of the user, where the changes are sensitive to the systolic pulse wave and reflected pulse waves; mounting the sensor in optical communication with a peripheral location of the body; acquiring a measurement signal from the noninvasive sensor system during a data acquisition period of at least one cardiac cycle of the patient to obtain an optical pulse plethysmogram; determining the presence of left ventricular outflow tract obstruction by evaluation of the optical pulse plethysmogram using a left ventricular outflow tract assessment system; providing the output of the left ventricular outflow tract assessment system to a user .
  • the left ventricular outflow tract assessment system further considers ancillary information in determining the presence of left ventricular outflow tract obstruction.
  • the optical measurement system uses pulse enhancement techniques to improve signal quality.
  • Some embodiments further comprise causing the patient to perform one or more volitional patient maneuvers to alter venous return during the data acquisition period.
  • the one or more volitional patient maneuvers comprises a change in body position
  • Some embodiments further comprise providing a resistance breathing device, and wherein the one or more volitional patient maneuvers comprises the patient using the resistance breathing device.
  • the peripheral location of the body is a finger. In some embodiments, the peripheral location of the body is the ear or ear canal.
  • the peripheral location of the body is the retinal of the eye.
  • the left ventricular outflow analysis system comprises a prediction model that maps the optical pulse plethysmogram to the type of left ventricular outflow tract abnormality.
  • the prediction model comprises multiple hierarchical layers.
  • providing an optical measurement system comprises providing a noninvasive speckle sensor system sensitive to flow in peripheral arteries during both systolic and diastolic phases of the cardiac cycle.
  • FIG. 1 is an illustration of aortic stenosis and the flow impacts
  • FIG. 2 is a figure illustrating the silent progression of aortic stenosis
  • FIG. 3 is a table of current methods used to access aortic stenosis
  • FIG. 4 is a graph showing the differences between moderate and severe aortic stenosis
  • FIG. 5 is a pictorial representation of the aortic valves used in the in silico simulation
  • FIG. 6 is an in silico simulation of aortic stenosis at peripheral sites illustrating pressure and PPG waves
  • FIG. 7 is an in silico simulation of aortic stenosis at peripheral sites illustrating flow and PPG waves
  • FIG. 8 is an illustrative example of the impact of vascular aging on pulse waveforms
  • FIG. 9 is an illustration showing the impact of vasoconstriction and vasodilation on reflected waves
  • Fig. 10 is an illustration showing the size and shape impacts of changes in vascular tone
  • FIG. 11 is an illustration of a finger bases speckle measurement system
  • FIG. 12 is a graph showing representative SPG and PPG waveforms
  • FIG. 13 is an example of an eye imaging system using a mobile phone
  • FIG. 14 is an illustration of sampling in the ear canal with a pulse plethysmography system
  • FIG. 15 is an illustration of the impact of controlled breathing on cardiac function
  • FIG. 16 is a flow chart showing how volitional maneuvers could be used to improve diagnostic information
  • FIG. 17 is an illustration showing the impact of positional changes on blood distribution
  • FIG. 18 illustrates the relationships between pressure and volume during the cardiac cycle
  • FIG. 19 shows the relationships between EKG, PCG, and PPG and their associated time intervals
  • FIG. 20 shows the impact of hydrostatic pressure differences on pulse size
  • FIG. 21 shows the impact of hydrostatic pressure differences on pulse size
  • FIG. 22 is a diagram showing the measurement configuration elements
  • FIG. 23 is a flow chart of an example measurement process
  • FIG. 24 is a pictorial representation of the finger SPG measurement configuration
  • FIG. 25 is the detailed measurement configuration associated with the finger SPG measurement
  • FIG. 26 is a pictorial representation of the ear PPG measurement configuration
  • FIG. 27 Is the detailed measurement configuration associated with the ear PPG measurement configuration
  • FIG. 28 is a diagram showing a potential breathing protocol
  • FIG. 29 is a pictorial representation of the eye laser contrast speckle imaging configuration
  • FIG. 30 is the detailed measurement configuration associated with the eye laser contrast speckle imaging configuration
  • FIG. 31 is a pictorial representation of the dual eye measurement configuration
  • FIG. 32 is the detailed measurement configuration associated with the dual eye measurement configuration
  • FIG. 33 is an optical system layout enabling dual sampling of the retina
  • FIG. 34 is a pictorial representation of the chest PPG measurement configuration
  • FIG. 35 is the detailed measurement configuration associated with the chest PPG measurement configuration
  • FIG. 36 is a pictorial representation of the face iSPG measurement configuration
  • FIG. 37 is the detailed measurement configuration associated with the face iSPG measurement configuration.
  • FIG. 38 is an illustration showing outflow tract disease progression in two patients
  • FIG. 39 is a detailed measurement configuration illustrating the ability to create different measurement system based on measurement needs [75] Brief Description of the Invention.
  • the invention provides apparatuses and methods for determining structural and valvular abnormalities of the left ventricular outflow tract from noninvasive, peripherally obtained optical pulse plethysmogram.
  • the invention does not require direct imaging of the heart or invasively obtained pressure and flow measurements but rather uses peripherally located, noninvasive measurements of flow, volume, or a combination thereof.
  • the invention addresses historical limitations in noninvasive optical determination of structural and valvular abnormalities in the left ventricular outflow tract by (1) utilizing improved optical measurement systems, (2) sampling locations that maximize the information content of the pulse waveform, (3) conducting volitional patient maneuvers to improve the diagnostic ability of the system, and (4) utilizing pulse enhancement techniques. Unlike many other diagnostic methods that focus solely on the early systolic phase of the cardiac cycle, the invention can utilize the information for both the systolic and diastolic phases of the cardiac cycle.
  • Measuring or measurement process refers to the process of obtaining a signal from a sensor.
  • a measurement signal or measured signal is the raw data or information obtained from the sensor system during a measurement process. Analysis and assessment systems process measurement signals for desired measurement results.
  • a parameter is a value that characterizes, summarizes, defines, or describes the properties of an entity.
  • a parameter can be calculated from a measurement signal to describe the properties of the signal.
  • a parameter can also describe the properties of an individual (e.g., age, gender, weight, or the presence of a medical condition).
  • a plethysmogram is the time series of data enabling a graphical representation of either blood volume or blood flow changes over time.
  • a plethysmogram is synonymous with a waveform.
  • a plethysmograph is a device that measures and records plethysmograms.
  • Plethysmography is the process of using a plethysmograph to measure and record plethysmograms.
  • Noninvasive sensors refers to a class of sensors that can be used outside the body and are sensitive to blood flow and blood volume, cardiac function, and physiological signals.
  • Electrocardiogram is a test that records the electrical activity of the heart.
  • the measured signals can be used in both physiological assessments and the determination of cardiac fitness.
  • Phonocardiogram is a recording of the sounds made by the heart and are related to the mechanical activities of the heart. The measured signals can be used in both physiological assessments and the determination of cardiac fitness.
  • Seismocardiogram is a technique for recording and analyzing cardiac vibratory activity as a measure of cardiac contractile functions. The measured signals can be used in both physiological assessments and the determination of cardiac fitness.
  • Ballistocardiography is a technique for producing a graphical representation of the reaction of the body to cardiac ejection forces or the reaction of the body to the blood mass ejected by the heart with each contraction associated with arterial circulation. The measured signals can be used in both physiological assessments and the determination of cardiac fitness.
  • Vibrational and acoustic measures refers to those measurement technologies that are sensitive to the vibration generated by the heart and include phonocardiogram, seismocardiogram, ballistocardiography, or any other method that is sensitive to the vibrations or sound created by the heart.
  • Echocardiography is the use of ultrasound to investigate the action and functioning of the heart.
  • the measured signals can be used in both physiological assessments and the determination of cardiac fitness.
  • Speckle plethysmograph is a non-invasive device used to measure blood flow in the body. It works by using a laser or other light source to illuminate the skin and tissue, and then analyzing the scattered light patterns, or speckles, that are produced. This technique can be used to measure blood flow in various parts of the body, such as the hand, foot, or brain, and can provide important information about the function of the circulatory system and the health of tissues and organs.
  • a speckle sensor system creates a plethysmograph representing changes in blood flow.
  • Photo plethysmograph is an optical measurement system that measures changes in blood volume using changes in light absorption and can be used to measure blood volume in a transmission sampling mode and reflection sampling mode.
  • the measured signals, a plethysmogram can be used to calculate both physiological and cardiometric parameters for both physiological assessments and the determination of cardiac fitness.
  • Radar plethysmograph is a noninvasive millimeter-wave, radar-based device for the accurate measurement of arterial pulse waveforms. Radar plethysmography can be utilized at any location on the body where a pulse creates a detectable movement of the skin or tissue. A common location is to use the system as a wrist-worn device that positions the radar near the radial artery without touching the skin, allowing for interrogation of the pulse at close range without perturbing the pulse waveform.
  • Optical sensors refers to any optically based system that can be used to capture signals related to changes in blood volume, flow, or pressure in a measurement region of the individual, which changes are indicative of cardiac function.
  • Optical pulse plethysmogram is the graphical representation and associated data stream or signal obtained noninvasively via the use of optical systems that are sensitive to changes in blood volume or blood flow in a region of the body resulting from cardiac activity over the entire cardiac cycle.
  • Noninvasive optical sensor system is a noninvasive system for acquiring optical pulse plethysmogram data.
  • Ancillary information defines additional information used in the measurement process to include demographic parameters, health status measures, and other additional information that allows a more accurate and meaningful assessment.
  • Ancillary information can include medical history, physical examination findings, blood pressure, age, weight, gender, health status, disease conditions, medications, and height.
  • Ancillary signals pertain to different measurement methods and signals that provide additional information regarding cardiac or respiratory function. Examples include but are not limited to electrocardiogram, phonocardiogram, seismocardiogram, ballistocardiography, anemometry, and spirometry.
  • Volitional patient maneuvers are volitional actions performed by the patient that modify cardiac performance in a deterministic fashion by changing filling pressure, afterload pressure, or heart rate.
  • Resistance breathing refers to any breathing method that increases, decreases, or changes intrathoracic pressure over normal breathing and alters venous return.
  • a resistance breathing test can include inhalation resistance breathing or exhalation resistance breathing, independently or in combination. Resistance breathing is a method that can be used to change venous return to the heart and influences end-diastolic volume.
  • Paced breathing is a general term that applies to any method that defines a breathing rate and can include depth of breathing.
  • Controlled breathing is the process of combining elements of paced breathing with resistance breathing.
  • Hydrostatic positional change is a general term that applies to any process that changes the hydrostatic pressure in a vessel due to positional changes.
  • Vascular tone as used herein, are changes in the size of the arteries that impacts both the shape and the size of the arterial pulse waveform. Locations with reduced vascular tone changes include locations with highly consistent perfusion and reduced sensitivity to autonomic changes relative to peripheral sites such as the wrist and finger. Such locations are typically those supplied by the arterials supporting the brain. Specific examples include the ear canal, tympanic membrane, retinal vessels, inter-month vasculature, and the nasal septum.
  • Tri-layered vessels refers to blood vessels comprised of three layers: the tunica intima, the tunica media, and the tunica adventitia. Tri-layered vessels include arteries, arterioles, venules, and veins but do not include capillaries, which are comprised of a single layer of endothelial cells.
  • Transmission dominant sampling refers to optical sampling of the tissue where the majority of photons penetrate and travel through the tissue, interacting with (i.e., reflected by, scattered by, or absorbed by) tri-layered vessels.
  • Transmural pressure adjustment refers to the ability to adjust the transmural pressure at the sight of sampling based on anatomical and physiological characteristics. For example, the physical size of the finger can impact the pressure exerted by a spring, and the patient's blood pressure will impact the ideal transmural pressure for optimal signal quality.
  • Peripheral sampling locations refers to the areas of the body that are farther from the center, such as the limbs and extremities.
  • the peripheral sampling locations also include organs and tissues that are located away from the central nervous system, such as the muscles, skin, and blood vessels in the limbs.
  • Central body location refers to the core of the body, which includes the brain, spinal cord, and other organs and tissues located near the center of the body, such as the heart, lungs, and liver.
  • LVOT Left ventricular outflow tract
  • Structural and valvular heart abnormalities in the left ventricular outflow tract refer to abnormalities that create deviations from normal left ventricular flow.
  • Structural obstructions are commonly defined based on the location of the obstruction and include entities located at the aortic valve level (valvular), in the ascending aorta (supravalvular), and in the proximal portion of the left ventricular outflow tract (subvalvular).
  • Valvular abnormalities can include aortic valve stenosis, mitral regurgitation, aortic regurgitation, and mitral stenosis.
  • Left ventricular outflow tract anomaly is any abnormality that impacts blood flow during ventricular contraction.
  • the systolic pulse wave is the pulse wave that is generated by the contraction of the left ventricle of the heart. When the left ventricle contracts, it pumps blood out into the aorta, creating a pressure wave that moves from the aortic value to the ascending aorta and into the periphery.
  • the reflected pulse waves or reflected waves are waves of pressure that are generated when blood flows through the arteries in the human body. As the blood flows through the arteries, it encounters bifurcations, elasticity changes, and changes in the diameter of the arterial lumen, which can cause the pulse wave to be reflected.
  • Arterial tree transformations are the changes in the shape of the aortic pulse waveform that occur as the pulse travels away from the heart.
  • the transformation of the pulse waveform is due to many parameters, including the length of travel, the pressure in the vessel, and the characteristics of the conduit vessel, including stiffness.
  • Patient-specific transformations are those transformations influenced by the anatomical and functional characteristics of the individual.
  • Anatomical differences can refer to the vessels' size, length, and shape.
  • Functional differences can include differences in stiffness/elasticity. These functional properties are influenced by age, gender, the presence of hypertension, and other disease conditions.
  • Late systole refers to the time from the point of maximum flow to the closure of the aortic valve.
  • a pulse waveform as used herein, is generic for waveforms resulting from cardiac activity and is not singularly associated with pressure. Pulse waveforms can be associated with pressure, volume, and flow.
  • a sensor system refers to software and hardware that measures the physical or electrical characteristics of cardiac function that enables an assessment for left ventricular outflow tract abnormalities.
  • the sensor system enables the sampling and recording of flow, volume, or pressure from a peripheral location.
  • Capabilities of the sensor system can include but are not limited to sampling, conversion, filtering, amplification, signal quality assessment, processing, and recording.
  • a sensor system for optical measurements could be composed of an emitter, detector, power supply, and microcontroller containing one or more CPUs (processor cores) along with memory and programmable input/output peripherals and RAM.
  • CPUs processor cores
  • RAM programmable input/output peripherals and RAM.
  • a sensor control system refers to software and hardware that is designed to control one or more elements of the sensor system. In most implementations, the control system regulates the operation of the sensor system based on input or logic. The logic element is often implemented via a microcontroller with associated software representing the logic needed for operation.
  • the sensor control unit may utilize a microprocessor, a programable data processor, or a computer to process and analyze data from the sensors, and to make sensor operational changes or decisions based on the data.
  • the sensor control system can modify the operation of the sensor system to enable different data acquisition modes, change the length of data acquisition, and initiate changes in the sensor used for signal measurement.
  • the data acquisition period is the time duration needed to acquire a measurement signal for subsequent assessment and analysis.
  • the left ventricular outflow tract assessment system refers to software and hardware that processes measured signals, including ancillary information, if desired, to determine the presence or absence of a left ventricular outflow tract abnormality and may determine the type of abnormality present.
  • Morphological waveform analysis is a method to provide insight into the behavior and characteristics of an underlying system by analyzing the time-varying signals produced by that system. By decomposing the signal into its constituent waveform shapes, or morphs, and analyzing the properties and characteristics of these morphs, it is possible to gain a better understanding of the processes and mechanisms that are driving the system. Morphological waveform analysis can be a valuable tool for understanding the behavior of complex systems such as the human circulatory system and for identifying patterns and trends within the signals that are produced during normal and abnormal conditions.
  • the left ventricular outflow tract reporting system refers to hardware and software that provides information back to the designated person or designated system.
  • the reporting system may use a designated graphical interface or may transmit information via Wi-Fi or Bluetooth to other display or presentation systems.
  • the designated person can be the patient, medical staff, or provider.
  • a designated system can include a screen display, printer, secondary data repository, or electronic medical record.
  • the invention relates to a simple and noninvasive screening and diagnostic test for the presence of structural and valvular heart abnormalities in the left ventricular outflow tract.
  • Left ventricular outflow tract obstruction is a condition in which there is a blockage or narrowing of the outflow tract of the left ventricle, which is the main pumping chamber of the heart. This narrowing can cause a reduction in the amount of blood that is pumped out of the heart, leading to symptoms such as shortness of breath, chest pain, fatigue, and can lead to heart failure and death.
  • aortic stenosis including auscultation murmurs
  • auscultation murmurs is specific to the systolic phase of the cardiac cycle, with the described variances being associated with a central measurement location.
  • a typical disruption of aortic stenosis describes the pulse waveform in the aorta.
  • Aortic stenosis is characterized by a diminished and delayed aortic pulse.
  • FIG. 4 shows the distinct differences between moderate and severe aortic stenosis. With further stenosis, the ejection period increases, the pressure peaks later, and the dicrotic notch become less apparent. It is important to note that the murmur often associated with aortic stenosis is a systolic ejection murmur.
  • Noninvasive Assessment at Peripheral Locations In contrast to historical approaches, the invention focuses on the changes occurring over the entire cardiac cycle with a focus on late systole and diastole.
  • Flow variances at the aortic valve are amplified as the systolic pulse wave moves to the periphery due to a combination of the ventricular-aortic interaction, pulse augmentation, and reflected pulse waves. Reflections of the pulse wave play a role in pulse amplification/augmentation in the arterial system. When the pulse wave travels through the arterial system, it encounters a series of branching vessels, changes in vessel diameter, and arterial stiffness. These changes cause reflected pulse waves, leading to the formation of multiple wave fronts.
  • the reflected pulse waves interact with the forward-moving pulse wave (systolic pulse wave) and amplify or attenuate the pressure and alter the blood flow in the arterial system. This interaction can be complex and depends on many factors, including the magnitude and timing of the reflected pulse waves, the stiffness of the arterial walls, and the flow of blood through the vessels.
  • FIG. 5 is a pictorial representation of the aortic valves simulated.
  • FIG. 6 illustrates the results of the in silico analysis for different peripheral sampling sites and shows the resulting pressure profiles and PPG waveforms. Examination of the pressure profile in the ascending aorta, 601, shows agreement with the invasive measurements reproduced in FIG. 4. Specifically, the ejection period increases, the pressure peaks later, the rise in rate of rise in aortic pressure is slower, and the dicrotic notch become less apparent.
  • PPG waveform was simulated for the area near the artery.
  • PPG is a volume-based measurement based on changes in absorbance
  • the profiles are similar but have distinct differences.
  • the stenosis PPG profile from the chest, 609 mimics previously reported in-vivo pulse profiles with a limited initial rise and a reduction in the dicrotic notch.
  • PPG waveforms for the wrist and finger, 610 show differences in the pulse waveform, but shapes are similar in form and appear to be time-shifted.
  • the PPG measurements from the eye show differences in the shape during the entire cardiac cycle, 612, and the ear, 611, as shape and inflection differences.
  • FIG. 7 is similar information but contains information on the flow characteristics on the left side of the page.
  • the inclusion of flow characteristics or flow profiles aids the determination process as it can be measured in the periphery by speckle plethysmograph and generally illustrates more distinct differences when PPG signals.
  • Aortic stenosis impacts flow, so the detection of aortic stenosis by flow bases techniques makes intuitive sense.
  • the flow rise during early systole is different with a measurable slope difference.
  • the peak of the location of maximum flow is delayed, and decreasing flow during late systole and diastole is different.
  • the flow curves of 702 can be easily scaled in the x and y dimension to create significant overlap. This fundamental difference in shape can be used to determine the presence of aortic stenosis.
  • the circle of Willis is a unique structure as most arteries are based on unidirectional flow while the circle of Willis supports bidirectional flow which can result in the collision of forward traveling waves. This complex flow pattern creates the odd flow pattern present in the ophthalmic artery, 703.
  • Pulse pressure amplification is strongly influenced by the rate of increase/ decrease in blood flow in the ascending aorta.
  • Pulse pressure amplification is a phenomenon that occurs when blood flows through a tapered artery. It refers to the increase in pulse pressure, or the difference between systolic and diastolic blood pressure, as the blood flows through the artery. This increase in pulse pressure is caused by the narrowing of the artery, which leads to an increase in arterial resistance and a decrease in arterial compliance. As the blood flows through the narrow section of the artery, it encounters increased resistance and is forced to exert a greater pressure to continue flowing. This results in an increase in systolic blood pressure, while the diastolic blood pressure remains relatively unchanged.
  • Pulse waveform distortion in arteries is caused by reflections of the pulse wave as it travels through the arterial system. These reflections can occur at points where there are changes in the diameter or elasticity of the arterial walls, or where the arterial tree branches.
  • a pulse wave When a pulse wave is transmitted through the arterial system, it travels at a certain velocity. If the arterial walls are uniform in diameter and elasticity, the pulse wave will travel smoothly without any significant distortion. However, if there are changes in the diameter or elasticity of the arterial walls, or if the arterial tree branches, the pulse wave will be reflected back towards the heart. These reflections can cause the pulse waveform to become distorted, resulting in changes in the shape and amplitude of the pulse wave.
  • FIG. 8 is an illustrative example of the impact of vascular aging and the stiffening with age that occurs. As can be seen in the figure, the pulse pressure peaks earlier in the younger individual, and the pulse pressure is increased in the older patient.
  • an element of the invention is the procurement of signals and information as well as analysis methods that allow the system to determine the difference due to aging or that resulting from a left ventricular outflow tract obstruction.
  • the invention seeks to mitigate the measurement impact of patient-specific differences
  • the left ventricular outflow tract assessment system may use ancillary information to include both anatomical and functional information to compensate for these differences.
  • Within-patient pulse transformations can occur with changes in physiological status. These changes can impact cardiac function resulting in pulse wave changes unassociated with left ventricular outflow tract abnormalities.
  • Physiological parameters include but are not limited to blood pressure, body temperature, breathing rate, interbeat time interval, heart rate, blood oxygen saturation, body position, interbeat time interval variability, cardiorespiratory phase, and sympathetic and parasympathetic tone.
  • the measurement process is facilitated by having the patient in a basal physiological state.
  • a basal state is defined as resting, unstressed, with the presence of cardiac vagal control resulting in respiratory sinus arrhythmia and with venous return at or near maximum capacity.
  • Vascular tone is an important parameter as changes in vascular tone impact the peripheral pulse waveform. Changes in vascular tone impact both the shape of the waveform and also the ability to detect the wave. Peripheral vasoconstriction produces an increase in the amplitude of the reflected wave. Peripheral vasodilation reduces the amplitude of the reflected wave and delays its return, see FIG. 9. In addition to the shape changes illustrated, the size of the pulse wave changes dramatically with the vascular tone, see Error! Reference source not found.. Changes in vasodilation create additional variances in the shape of the pulse waveform and are typically more pronounced in the periphery. Thus, the invention seeks to mitigate the measurement impact of changes in vascular tone by hearting the hand or using sampling sites that have diminished changes in vascular tone.
  • Flow Measurements The ability to measure flow in the vascular system has recently been developed using optical speckle measurements.
  • Optical or laser speckle measurements are techniques used to determine blood flow in the body by analyzing the movement of red blood cells within a vessel. These techniques rely on the principles of light scattering and interference. When light is shone on a sample, it is scattered in all directions by the particles within the sample. This scattering is known as speckle, and it can be used to analyze the movement of particles within the sample. In the case of blood flow measurements, the particles being analyzed are red blood cells.
  • FIG. 11 is an illustration of a speckle based measurement system for use on a finger, where the laser diode and camera sensor are in optical communication with the finger.
  • Speckle plethysmography is a flow-based measurement and has some additional benefits relative to photoplethysmography (PPG) in that it is less sensitive to vascular changes and vascular compliance.
  • PPG photoplethysmography
  • Dunn et al. state that SPG "provides an improved signal-to-noise ratio and robustness in the presence of motion artifact and cold temperatures as compared to PPG.”
  • FIG. 12 shows the differences in pulse waveforms between SPG and PPG with an EKG as a reference element.
  • Ghijsen et al. demonstrated reduced sensitivity to vasoconstriction.
  • the SPG waveform maintained a robust signal-to-noise ratio (SNR) under conditions of significant vasoconstriction relative to PPG, which failed to provide any reading.
  • SNR signal-to-noise ratio
  • SPG Wearable speckle plethysmography
  • Speckle plethysmography can be used in several sampling configurations, including transmission sampling through the tissue, reflectance sampling, and imaging modalities.
  • Dunn et al. in a second publication demonstrate that "SPG has a much larger SNR than PPG, which may prove beneficial for noncontact, wide-field optical monitoring of cardiovascular health.” Cody E. Dunn, Ben Lertsakdadet, Christian Crouzet, Adrian Bahani, and Bernard Choi, "Comparison of speckleplethysmographic (SPG) and photoplethysmographic (PPG) imaging by Monte Carlo simulations and in vivo measurements," Biomed. Opt. Express 9, 4307-4317 (2018).
  • Laser speckle contrast imaging is a noninvasive imaging technique used to measure blood flow in many body locations including the face and retinal.
  • Laser speckle contrast imaging has the ability to determine a pulse signal in distinct retinal vessels over the cardiac cycle.
  • Laser speckle contrast imaging has demonstrated the ability to reliably reveal retinal blood flow dynamics with high spatiotemporal resolution and discriminate between arterial and venous blood flow patterns in the retina. Since retinal blood flow fluctuates over a heartbeat, monitoring the temporal dynamics of retinal vessels creates the ability to procure a pulse plethysmogram that is sampled close to the heart and in an area with exceptional temperature and vascular tone stability.
  • Laser Doppler techniques are based on the optical Doppler effect, which relies on the reflection of a high coherence laser beam scattered in vivo on vascular tissue and captures the shift of the underlying moving red blood cells.
  • the back-scattered light gives a measure of both the incident light (vessel wall) as well as the shifted light (red blood cells), thus providing a measure of relative blood flow, blood volume, and blood velocity within a specified region of the retina.
  • An absolute red blood cell velocity is obtainable by means of bidirectional laser Doppler velocimetry, when the light scattered from the erythrocytes is detected from two directions. For the volumetric blood flow rate calculation, an accurate measure of the diameter is required.
  • Laser Doppler flowmetry does not rely on vessel diameter measurement but is based on the intensity of signal derived from the red blood cell volume and velocity. Combining the laser Doppler flowmetry with laser scanning tomography, a two-dimensional mapping of retinal blood flow can be obtained, resulting from blood flow measurements based on both single and multiple scattering events from many red blood cells. Local frequency components of the reflected light are obtained at each scanning point and combined with blood velocity.
  • Other Doppler Techniques including combining OCT with the Doppler technique and laser Doppler holography, have demonstrated flow velocity measurements in the eye.
  • OCT optical coherence tomography
  • PPG Photoplethysmography
  • PPG Photoplethysmography
  • the measurement is achieved by shining a light onto the tissue and measuring the amount of light that is absorbed.
  • the absorbance of light is directly related to the amount of blood present in the tissue.
  • PPG allows for the continuous measurement of blood volume in human tissue by measuring the absorbance of light at regular intervals. The method can be used to measure changes in blood volume resulting form cardiac function.
  • Imaging photoplethysmography can be used to obtain pulse waveforms from many locations on the human body, including the hand, face, eyelids, and the eye.
  • Imaging photoplethysmogram is a remote and non-contact alternative to the conventional PPG in humans. iPPG is typically acquired using a video camera under dedicated or ambient light. The video is typically usually recorded from palm or face regions. The technique has also been used to assess retinal blood flow.
  • FIG. 13 is an example of an eye imaging PPG system using a mobile phone and an example of the resulting photoplethysmograph.
  • Video images were obtained with a handheld, non-mydriatic fundus camera.
  • the resulting video was processed by amplifying the pulse signal using RGB color panels and processing a region of interest around the optic nerve.
  • the resulting signal was high-pass filtered, and eye blinks were removed.
  • the resulting signal for a person with no left ventricular outflow tract abnormality shows a pulse with a clear dicrotic notch, identified by the arrows.
  • a variety of camera and optical systems can be used to obtain an image-based photoplethysmograph by capturing a series of fundoscopic images or a video that enables subsequent processing for determining a pulse plethysmogram.
  • a standard fundoscopic camera that can take repeat images at an adequate sampling rate enables the creation of a pulse waveform that can be used to screen for left ventricular outflow tract abnormalities.
  • Morgan, William H., et al. have also shown pulse measurements for the eye. Photoplethysmographic measurement of various retinal vascular pulsation parameters and measurement of the venous phase delay.
  • the process can be used at the individual vessel level as shown in Fig. 1 of Tornow's publication or based upon the entire image.
  • the pulse waveform can also be calculated from the pulsatile changing light reflection due to the pulsatile changing amount of blood in the retinal vessels as well as changes in the location of various tissue types.
  • the use of larger regions of interest for optical processing requires less stability of the measurement platform as it is not particular for a specific artery segment.
  • An additional system with improved measurement capabilities includes the ability to measure arterial waveforms in both eyes concurrently. Because aortic stenosis often creates peak velocity jets and there is an asymmetry in the vascular access to the eyes, the concurrent measurement of valvular pulses can provide additional diagnostic information.
  • the parallel video acquisition of both eyes simultaneously can enable the comparison of PPG signals between both eyes with a high temporal and spatial resolution for the detection or deviation from symmetry.
  • Tornow et al. have demonstrated that differences in eye pulse asymmetries can occur in the presence of carotid artery stenosis. Tornow, Ralf-Peter, Jan Odstrcilik, and Radim Kolar. "Time-resolved quantitative inter-eye comparison of cardiac cycle-induced blood volume changes in the human retina.” Biomedical Optics Express 9.12 (2016): 7237-7254.
  • a system for obtaining such images can use a headset similar to a virtual reality headset such that the patient can focus on a moderately dark screen with limited eye movement.
  • the use of a moderately dark screen facilitates pupil dilation. Additionally, instructions associated with cardiac maneuvers can be supplied to the patient.
  • a funduscopic imaging system in the headset enables the acquisition of fundoscopic images over time as the patient views the screen.
  • Multiple processing methods are suitable for the determination of pulse waveforms for the eye. These methods can use a single location, a single vessel, a region of interest, or the entire image. Additionally, these data can be acquired with no pressure applied to the eye or a small increase in intraocular pressure to further facilitate a decrease in arterial transmural pressure and reduce contributions from venous sources.
  • Ear canal sampling The ear, specifically the auditory canal, is a desirable sampling location due to its proximity to the heart, consistent perfusion with minimal changes in vascular tone, and decreased transmural pressure when standing or sitting.
  • FIG. 14 illustrates the sampling location in the auditory canal where the sensor and detector are in optical communication with the tissue. Additionally, waveform differences resulting from reflections were evident in the in silico simulations.
  • Eye Sampling The retinal vessels in the eye represent another sampling location that exhibits consistent perfusion with reduced changes to local vascular tone and decreased transmural pressure when the patient is sitting or standing. Importantly the ability to access the arteries and arterioles of the eye via an "optical window” has a multitude of advantages. Other sampling locations on the body necessitate measurement through the skin.
  • Chest The chest represents a unique sampling location due to the minimal distance traveled in the arterial vasculature. Additionally, the procurement of ancillary information including electrocardiogram, phonocardiogram, seismocardiogram, and ballistocardiography are easily obtained from the chest.
  • Cardiac maneuvers are volitional actions performed by the patient that modify cardiac function in a deterministic fashion by changing filling pressure, afterload pressure, or heart rate. For example, the Valsalva maneuver has been used during dynamic auscultation to help distinguish different cardiac conditions.
  • the murmur of aortic stenosis typically increases with maneuvers that increase left ventricular volume and contractility (e.g., leg-raising, squatting, Valsalva release, after a ventricular premature beat) and decreases with maneuvers that decrease left ventricular volume (Valsalva maneuver) or increase afterload (isometric handgrip). These dynamic maneuvers have the opposite effect on the murmur of hypertrophic cardiomyopathy, which can otherwise resemble aortic stenosis.
  • the murmur of mitral regurgitation due to prolapse of the posterior leaflet may also mimic arterial stenosis.
  • Maneuvers can be used to change the filing pressure into the hearts and the afterload in a deterministic fashion to create additional diagnostic information based on the pulse waveform.
  • the pulse waveform will change in the diseased and normal heart as the patient performs certain maneuvers.
  • the change in the pulse waveform can be used as a clinical tool during testing to aid in diagnosing the specific heart abnormality.
  • the following maneuvers create deterministic changes impacting cardiac function.
  • the type of preload or afterload change is specified with each maneuver and the typical impact on heart murmur intensity is included.
  • Handgrip Increases afterload. Hand gripping increases the strength of aortic regurgitation, mitral regurgitation, and ventricular septal defect murmurs. It decreases the intensity of murmurs due to hypertrophic obstructive cardiomyopathy and mitral valve prolapse.
  • Squatting Increases preload. Squatting increases the intensity of aortic stenosis, mitral stenosis, aortic regurgitation, and mitral regurgitation. It decreases the strength of murmurs due to hypertrophic obstructive cardiomyopathy and mitral valve prolapse.
  • Valsalva Decreases preload. Valsalva increases the strength of murmurs due to hypertrophic obstructive cardiomyopathy and mitral valve prolapse. It decreases the intensity of aortic stenosis, mitral stenosis, aortic regurgitation, mitral regurgitation, and ventricular septal defects.
  • Resistance breathing, paced breathing, or controlled breathing can be used to create deterministic changes in cardiac function. Changes in intrathoracic pressure influence the venous flow to the heart. For example, high intrathoracic pressure obtained during exhalation against resistance will decrease the venous return to the heart. Control of the rate and degree of resistance on either inhale or exhale or both creates repeatable changes to cardiac function that can be used to facilitate the detection and diagnosis of left ventricular tract obstructions.
  • a resistance breathing device is used by the patient and is used to create systematic airway pressure changes.
  • a resistance breathing device can be used to create exhalation resistance to create an abnormal increase in intrathoracic pressure during exhalation.
  • such a device can create inhalation resistance resulting in an abnormal decrease in intrathoracic pressures.
  • the system can use different levels of resistance over the course of the protocol. Multiple methods of implementation exist for altering intrathoracic pressure above normal levels, resistance breathing devices can include the use of pressure threshold, flow-independent pressure valve, air restriction mechanisms, and any mechanism that cause an increase in pressure during normal breathing. Additionally, the term resistance breathing covers the process of creating a change in intrathoracic pressure where little or no air movement occurs for a period of time.
  • Paced breathing applies to any method that defines a breathing rate and can include depth of breathing. Paced breathing is typically slow at a rate between 5 and 7 breaths per minute. With normal breathing, the rate is about 12 to 14 breaths a minute. Paced breathing can include defined changes in the rate and an asymmetric breathing profile; for example, the exhale is 8 seconds while the inhale is 5 seconds.
  • Controlled breathing is the process of combining resistance and paced breathing to influence cardiac changes.
  • the "controlled” aspect is a system or method of breathing that dictates breathing rate and creates an intrathoracic pressure change that is greater than normal breathing. Examples of controlled breathing include but are not limited to a mi ni-M ueller inhale against resistance using a pressure threshold, but flow independent value followed by a mini-Valsalva against resistance using a pressure threshold, but flow independent value at a rate of 7 breaths per minute.
  • the above mini-Mueller and mini-Valsalva controlled breathing system can be configured so that pressures are the same on inhalation and exhalation (symmetric) or different on inhalation and exhalation (asymmetric).
  • the resistance pressure can be modified to facilitate different defined intrathoracic pressure changes.
  • the resistance pressures can magnify normal changes in intrathoracic pressure leading to more significant changes in venous return, thus effectively creating an improved signal-to-noise measurement.
  • These larger than normal physiology changes in venous return subsequently create larger changes in stroke volume and facilitate hemodynamic assessment.
  • Controlled breathing typically at six breaths per minute, can be implemented at zero resistance or multiple defined levels.
  • a significant benefit of a controlled breathing protocol at different resistance levels is the creation of a moderately consistent breathing process with multiple levels of evaluation.
  • Kimura et al. demonstrated that changes in inspiration between diaphragmatic versus chest wall expansion influenced inferior vena cava diameter and would thus influence the venous return curve.
  • Kimura, Bruce J., et al. The effect of breathing manner on inferior vena cava diameter.” European Heart Journal-Cardiovascular Imaging 12.2 (2011): 120-123.
  • the present invention can reduce the influence of subject breathing type by using the information at two different pressure levels to help normalize subject-specific breathing differences. Additionally, as shown in the Campbell diagram previously, changes in lung volume interact with lung and chest wall compliance. Therefore, dramatic changes in tidal volume will have a direct impact on intrathoracic pressure. Therefore, a benefit of the controlled breathing system is to create a repeatable, defined intrathoracic pressure changes where tidal volume differences are minimized.
  • Exercise can also be used to induce changes in cardiac function for additional diagnostic capabilities. Exercise creates various physiological changes, including increased heart rate, heart contractility, decreased systemic vascular resistance, and increased blood pressure.
  • Amyl nitrate is a drug that decreases afterload. Amyl nitrate increases the intensity of aortic stenosis, hypertrophic obstructive cardiomyopathy, and mitral valve prolapse. It decreases the severity of aortic regurgitation, mitral regurgitation, and ventricular septal defects.
  • FIG. 16 illustrates a method where cardiac maneuvers are used to improve the diagnostic resolution of the system to identify the specific left ventricular outflow tract abnormality.
  • Positional changes are a type of volitional change that increases the filling pressure to the heart as the patient moves between standing, sitting, and supine postures. Movement from the standing position to the supine position results in the translocation of approximately 300 ml to 500 ml from the lower extremities towards the intrathoracic vessels and produces an increase in venous return and cardiac preload. According to the Frank-Starling law, there is a positive relationship between preload and systolic volume; accordingly, the greater the ventricular preload (and therefore the degree of cardiac muscle stretch), the greater the systolic volume ejected. Positional changes and their impact on cardiac function are illustrated in FIG. 17.
  • Ancillary Signals pertain to measurable signals associated with cardiac or respiratory functions. Determining left ventricular outflow tract obstructions can be enhanced through ancillary signals such as an electrocardiogram (EKG), phonocardiogram, or seismocardiogram. In the EKG, variances in T-wave and QT interval have shown some correlation to aortic stenosis. EKG measurement also enables the determination of pulse transit time, which has shown a correlation with arterial stiffness and functional properties of the arterial tree. Phonocardiography, the recording of all the sounds made by the heart during a cardiac cycle, and seismocardiography, the recording of body vibrations induced by the heart, can also be used for data augmentation.
  • EKG electrocardiogram
  • phonocardiogram phonocardiogram
  • seismocardiogram seismocardiogram
  • FIG. 18 shows a pressure, volume and timing diagram of the cardiac cycle, as well as EKG and phonocardiogram signals.
  • FIG. 19 shows the relationships between certain measured parameters and the ECK, PCG, and PPG signals and serves as reference for a variety of determined time intervals.
  • Ancillary Information Including vital signs, anatomical and functional information, physiological, and demographic information can help with the evaluation process.
  • Potential ancillary information can include blood pressure, age, gender, health status, medications, and height. This ancillary information can provide important information associated with understanding the type and degree of pulse waveform transformation expected for a similar individual with a ventricular outflow tract obstruction. As shown in FIG. 8, age is a factor in accessing the morphology of the waveform. Another important factor is blood pressure, which influences pulse wave velocity and impacts forward and reflected wave propagation.
  • TMP vascular transmural pressure
  • VAR local venoarterial reflex
  • TMP decreases in TMP trigger the myogenic response, i.e., the relaxation of the smooth muscles in artery walls
  • vessel compliance is a function of TMP
  • decreases in TMP increase arterial compliance such that a given change in arterial pressure results in a larger change in arterial volume.
  • TMP can be reduced by applying external pressure at the measurement site or raising the elevation of the measurement site relative to the heart to decrease hydrostatic pressure.
  • External pressure pulse enhancement The application of external pressure at the sampling sight can be used to reduce the TMP.
  • the optimal external pressure is typically greater than the venous pressure but less than the arterial diastolic pressure; pressures beyond this point will begin to occlude flow and distort the pulse waveform.
  • 95% of individuals aged 18-99 years have a diastolic pressure above 70 mmHg. If the sampling site is near or below the level of the heart, external pressures in the range of 50 mmHg can be appropriate to increase the magnitude of arterial pulsation.
  • FIG. 20 shows the detector signal from an adjustable PPG ring worn at the base of the finger.
  • the signal has been band-pass filtered to focus on the pulsatile component. Roughly every 45 s, the ring is tightened incrementally on the wearer's finger via a ratcheting mechanism on the ring band. These tightening events are denoted by gray rectangles, 203.
  • the wearer's reported subjective experience associated with the different levels of tightness is indicated below the graph. Initially, in period 201, the ring is reported by the user to be "very loose,” and the magnitude of the pulse is -100 detector counts. After several tightening events, the user reports that the ring makes "stable contact” with the finger.
  • the pulse size at this period (202) is -150 counts. After this point, each tightening event increasingly changes the TMP through the applied external pressure, as evidenced by the increase in pulsatile signal size. When the ring is reported by the user to be "very tight,” the pulse size increases to -1000 counts (period 203). After further tightening, the user reports feeling pulsations in the finger, an indication that the external pressure is approaching arterial diastolic pressure. Cumulatively, the tightening events produced a 10% reduction in the circumference of the ring and created a 10-fold increase in signal size is due to the decrease in arterial TMP caused by the increased external pressure at the sampling site.
  • the measurement device includes a system and mechanism for decreasing the transmural pressure (TMP) for maximal signal quality by adjusting the TMP based on patient physiology.
  • TMP transmural pressure
  • the system allows patient-specific adjustments to the TMP that compensate for anatomical differences, blood pressure differences, and other patientspecific nuances. Adjustments can be manual or automatic in nature, facilitating the procurement of high-quality pulse waveforms by increasing the TMP to a pressure that does not compromise arterial flow. It is important to note that the external pressure resulting in a maximal pulse waveform is not desired for long-term monitoring as the patient may report feeling pulsations in the finger, which may be slightly disconcerting. As the device is a designated test over a limited period, this discomfort is viewed as acceptable. The force exerted by a typical fingertip oximeter is commonly less than optimal due to potential discomfort of the user as they are used for longer term monitoring, and the spring used to hold the device on the finger is not configurable based on patient specific characteristics.
  • FIG. 21 shows a second example of the effect of TMP on pulse size, in this case, using manipulations in hydrostatic pressure to alter the TMP.
  • FIG. 21 shows a band-pass filtered detector signal from a PPG ring worn at the base of the finger. The ring size is constant throughout the experiment, but the subject undergoes changes in arm positions, indicated by gray rectangles 2105. In period 2101, the arm hangs in a relaxed position at the subject's side.
  • the sampling site is estimated to be 50 cm below the right atrium of the heart, resulting in ⁇ 37 mmHg of additive pressure distending the walls of the veins and arteries due to the hydrostatic pressure exerted by the vertical columns of blood in these vessels.
  • the pulse size in this period is just under 400 counts.
  • the subject raises their hand such that the sampling site is roughly level with the shoulder.
  • the change in vertical displacement with respect to the heart decreases the hydrostatic pressure, decreasing the TMP accordingly.
  • the pulse size therefore increases by more than a factor of 2 to nearly 1000 counts.
  • the subject extends their arm to a comfortable position above their head.
  • the sampling site is now an estimated 77 cm above the right atrium, resulting in hydrostatic pressure of roughly -50 mmHg. This height reduces the TMP, which causes a further increase in the pulse size to roughly 1500 counts.
  • the subject slowly lowers their arm down. As would be expected, the pulse size gradually decreases.
  • Vasodilation by heating Heating the hand can cause vasodilation, which is the widening of blood vessels.
  • vasodilation which is the widening of blood vessels.
  • blood vessels dilate more blood can flow through them, which leads to an increase in pulse amplitude.
  • pulse amplitude is due to the increased blood flow and volume in the blood vessels.
  • tissues is exposed to heat, the blood vessels near the surface of the skin dilate to help regulate body temperature. As the blood vessels widen, more blood flows through them, leading to an increase in pulse amplitude.
  • Optical sampling design The physical configuration of light emitters and detectors in an optical system also plays an important role in determining the optical path length and the type of vessels sampled.
  • the system seeks to maximize the SNR related to flow abnormalities or pulse waveform abnormalities by a deeper sampling of larger vessels such as arteries and arterioles.
  • the apparatus used for auditory canal sampling can be inserted into the ear canal, and the relationship (distance and angle) between the detector and emitter is optimized for measuring information-rich and maximized SNR pulse waveforms.
  • the apparatus may also be configured to fit snugly within the auditory canal or expand after insertion. The application of mild positive pressure on the inside of the auditory enables stable contact of optical components and decreases transmural pressure across the vessels of interest.
  • Supine Position To assess a left ventricular outflow tract abnormality, maximizing the amount of blood ejected per beat is beneficial. The impact of a decrease in the cross-sectional area of the aortic valve could be minimal at low stroke volumes but will increase as the amount of blood that must pass through the valve with each beat increases. Placement of the patient in the supine position maximized stroke volume and is a method for maximizing pulse size. As the patient is stationary during this activity, it was not viewed as a volitional activity but rather a pulse enhancement activity. For the purpose of repeatable testing, the patient should be in a preload independent state. Preload independence defines a physiological state where the variations in cardiac filling pressures have minimal effect on stroke volume. Preload independence occurs during conditions of high venous return when the heart is filled at or around natural capacity. The location of the body in a supine position facilitates preload independence by increasing venous return.
  • Sensor control system controls the operation of the sensor system and ensures that an adequate measurement signal is obtained. Sensor control system will also acquire ancillary information and ancillary signals as necessitated by the measurement protocol. Additionally, the sensor control system may perform quality control on the measurement signal and optimization of the sensor system for optimal performance by altering the operational parameters. Operational parameters can include the optimization of light intensity, optimization of transmural pressure decrease, changing the optical focus in imaging situations, determining the region of interest in imaging applications, changing the duration of data acquisition, and the sampling rate of data acquisition. Additionally, the sensor control system can ensure that volitional activities are completed and correctly executes via assessment of the measures signal or the use of ancillary signals.
  • the left ventricular outflow tract assessment system can perform one or more of three related functions: the determination of the presence or absence of a left ventricular outflow tract abnormality of a flow anomaly, the classification of the anomaly, and provision of a metric regarding the severity of outflow tract obstruction.
  • Anomaly detection is the identification of optical pulse plethysmographs that deviate significantly from the majority of the data or normal physiology. The result is a two-class determination, normal versus abnormal. The process can be extended to multiple classes: normal, valvular obstruction, supravalvular obstruction, or subvalvular obstruction. Additional classifications could be added if desired clinically and supported by the measurement system.
  • the assessment system can produce a continuous assessment variable associated with the degree of obstruction. For example, the assessment system could provide an assessment of the aortic value area which corelates with the severity of stenosis.
  • the left ventricular outflow tract assessment system utilizes sophisticated analysis methods for the detection of a flow anomaly and the classification of the anomaly.
  • the assessment system performs mathematical data processing steps without patient/user involvement.
  • the analysis method can include many classes of models but can be broadly broken into “prediction models” and “matching models.”
  • Prediction models are constructed by determining the relationship between data or data features and desired output.
  • the determination of relevant data features can be facilitated by morphological waveform analysis.
  • Morphological waveform analysis is a technique used to analyze and understand the behavior of a time-varying signal by decomposing the measured signal into its constituent waveform shapes or "morphs.” This can be useful for identifying patterns or trends in the signal, as well as for identifying and isolating specific features or events within the signal that are associated with the measurement output of the system.
  • the process of morphological waveform analysis typically involves three main steps:
  • Decomposition The signal is decomposed into its constituent waveform shapes, or morphs, using a morphological filter. This filter is designed to identify and extract the underlying waveform shapes within the signal, and can be applied either in the time domain or the frequency domain.
  • Classification The extracted morphs are then classified based on their shape, size, and other characteristics, such as their duration, amplitude, or frequency content.
  • Morphological waveform analysis is particularly useful for analyzing signals that are complex or noisy, as it allows analysts to extract and analyze the underlying waveform shapes that contribute to the overall signal.
  • a prediction model is a mathematical model that uses a set of data features to generate a prediction result. These data features, also known as variables or predictors, can include any measurable attributes or characteristics of the data being analyzed.
  • the model uses a set of algorithms to analyze the relationships between the data features and the prediction result, and then generates a prediction based on that analysis. Examples of prediction models include regression models, where features are mapped to outputs through linear or non-linear relationships, as well as some machine learning models.
  • the goal of the prediction model is to accurately predict the outcome of a particular event, presence or absence of a left ventricular outflow tract abnormality or the type or severity of the abnormality.
  • the prediction model may predict the valve area in aortic stenosis.
  • the model can be applied to novel data without relying on training or reference data.
  • the development of training of the prediction model can use a variety of training techniques including supervised anomaly detection techniques, semi-supervised anomaly detection techniques, and unsupervised anomaly detection techniques.
  • Matching models are used to identify and match patterns or relationships between different pulse waveforms and the clinical condition, effectively creating a function map between the input and output variables.
  • Deep learning involves the use of artificial neural networks, which are designed to mimic the way the human brain processes information. These neural networks can be trained on representative data and can learn to recognize patterns and relationships, making them particularly well-suited for matching tasks.
  • Some common deep learning techniques used in the development of matching models include convolutional neural networks, recurrent neural networks, and autoencoders.
  • Recurrent neural networks are a type of artificial neural network that are particularly well-suited for processing sequential data. They are called “recurrent” because they have a feedback loop in their architecture, allowing them to retain information from previous time steps and use it to inform their processing of the current time step. This capability makes them effective at tasks involving time series.
  • RNNs One area where RNNs have been applied is in the analysis of physiological pulse data. For example, RNNs have been used to predict heart rate and respiratory rate from pulse waveforms. In these cases, the RNN can learn patterns in the pulse data over time, allowing it to make more accurate predictions. RNNs have also been used to classify pulse waveform patterns, such as identifying the presence of arrhythmias or identifying different types of arrhythmias. Overall, RNNs offer a powerful tool for understanding and interpreting physiological pulse data and are applicable to pulse plethysmograph data.
  • the useful features and representations are essentially learned by the model in training, along with the function that maps the inputs to the desired outputs.
  • the models are developed using the measured signals from the sensor system, in raw or conditioned data representations that contain the left ventricular outflow tract abnormality and an output variable indicative of the degree or presence of the left ventricular outflow tract abnormality. Because the relationship between input and outputs is often quite complex (involving thousands of weights in multiple hierarchical layers), the engineer or architect of the model might be completely unaware of the features or information that the model has extracted or how and why that information is combined to form the output.
  • Models using hierarchical layers can divide the data into levels, with each level representing a different level of aggregation or a different aspect of the data.
  • Hierarchical models allow for the modeling of both within-level and between-level variation and can account for the dependencies between observations at different levels.
  • Hierarchical models can be more complex than other types of models and can require more computational resources to estimate, but they can be useful for handling complex data and making nuanced predictions.
  • the desired output can be a continuous variable (e.g., a degree of flow abnormality) or a binary variable that takes on values of zero/one, indicating the presence or absence of a specific condition or state (e.g., the presence of a left ventricular outflow tract abnormality).
  • Predictive algorithms use mapping functions to define a mathematical function between inputs to outputs, where the inputs are the historical data and the outputs are the predictions.
  • the mapping function of a predictive algorithm is typically defined by a set of parameters that are learned from the historical data during the training process.
  • the set of parameters defines a mathematical mapping function between the input information (pulse plethysmogram) and information on the presence or absence, type of obstruction, or severity of a left ventricular outflow tract obstruction.
  • Different types of predictive algorithms have different types of parameters and different ways of learning them. For example, linear regression models have coefficients that are learned by minimizing the sum of squared errors between the predictions and the true values.
  • Decision trees have a tree structure that is learned by recursively splitting the data into subsets based on the values of the input variables.
  • Neural networks have weights and biases that are learned by adjusting the internal parameters of the network using an optimization algorithm such as gradient descent.
  • the output of the mapping function can be a binary output, a multi-class classification output or a continuous variable output. In the case of a multi-class classification the classification can be by the type of outflow tract obstruction.
  • mapping function can be used to make predictions on new input data by applying the learned parameters to the input data.
  • the predictions made by the algorithm are estimates of the future events or outcomes based on the historical data.
  • the left ventricular outflow tract assessment system can use one or more mapping functions to define a relationship between inputs (historical data) to outputs (predictions), with the function being defined by a set of parameters that are learned from the historical data during the training process.
  • mapping functions can be used to make predictions on new input data.
  • the implementation of the left ventricular outflow tract assessment system for use on a medical device can use a number of hardware and software elements, often present in a programable data processing system, including:
  • the left ventricular outflow tract assessment system uses a moderately powerful processor, such as a central processing unit (CPU) or a graphics processing unit (GPU), to handle the computations required by the algorithm during the prediction phase.
  • a moderately powerful processor such as a central processing unit (CPU) or a graphics processing unit (GPU) to handle the computations required by the algorithm during the prediction phase.
  • CPU central processing unit
  • GPU graphics processing unit
  • RAM randomaccess memory
  • the left ventricular outflow tract assessment system uses storage space to store the mapping function such as a deep learning algorithm and any additional data required by the algorithm during execution.
  • Connectivity If the left ventricular outflow tract assessment system needs to communicate with other devices or servers to obtain or transmit data, it needs appropriate connectivity options, such as Wi-Fi or cellular connectivity.
  • the left ventricular outflow tract assessment system can have an operating system that is compatible with the deep learning framework and libraries being used.
  • the left ventricular outflow tract assessment system can have the appropriate algorithm frameworks and libraries installed in order to execute the algorithm.
  • Examples of popular deep learning frameworks are TensorFlow, PyTorch, Caffe, etc.
  • the left ventricular outflow tract assessment system can have enough power supply to run the deep learning algorithm, as running deep learning algorithms can require high computational power and can drain the battery quickly.
  • Data pre-processing The left ventricular outflow tract assessment system canhave software that pre- processes the data before it is analyzed by the deep learning algorithm.
  • the requirements can vary depending on the specific algorithm and device. For example, a device that is designed to use a prediction algorithm can have different requirements than a device that is using a deep learning algorithm.
  • the left ventricular outflow tract assessment system includes the totality of activities that process the measured data and data inputs and applies calculations or a designated set of steps to determine the presence of a flow abnormality and, to the extent possible, the structural or valvular abnormalities causing the obstruction.
  • the left ventricular outflow tract assessment system can use a variety of inputs to include flow waveforms, volume waveforms, both volume and flow waveforms, measured signals obtained during volitional maneuvers, the inclusion of ancillary information and ancillary information.
  • the ability to conveniently detect structural and valvular abnormalities of the left ventricular outflow tract remains a desirable but currently unfulfilled objective.
  • the invention addresses historical limitations in noninvasive optical determination of structural and valvular abnormalities in the left ventricular outflow tract by (1) utilizing improved optical measurement systems, (2) sampling locations that maximize the information content of the pulse waveform, (3) conducting volitional patient maneuvers to improve the diagnostic ability of the system, and (4) utilizing pulse enhancement techniques.
  • the following example embodiments specifically address these historical limitations such that effective screening for left ventricular outflow tract abnormalities can be achieved.
  • the measurement system can be configured to provide the degree of measurement resolution needed.
  • the measurement configuration used can be determined on a per patient basis, at the clinic level or at the health system level and is based in part on the desired performance of the system, the cost of the instrumentation, and the sophistication of the operator.
  • the system can be configured to provide a simple screen test for any type of left ventricular outflow tract abnormality.
  • the objective of the measurement can be to detect any abnormality so subsequent echocardiogram follow-up is initiated. In such a scenario, the objective is to have high sensitivity for left ventricular outflow tract abnormalities and reasonable specificity.
  • the objective can be to determine the location of the left ventricular outflow tract and to provide some staging information regarding severity.
  • FIG. 22 is an illustration to show the measurement configuration concept. At the top of the diagram is the measurement system to be selected for procuring the measurement signal. As the bottom of the graph is the sampling location. The schematic illustrates that one type of measurement device is used, and one location is sampled. Multiple measurement systems and locations could be used, but for communication purposes and simplicity of illustration, only single selections will be discussed. Additional or ancillary information and ancillary information is pictorially illustrated on the left side of the illustration. Correspondingly, the pulse enhancement techniques can be selected if needed from the right side of the illustration.
  • FIG. 22 shows an example of one proposed flow chart of the measurement process.
  • the measurement configuration defines the operation of the system.
  • the procurement of the measurement signal is managed by sensor control system, and the resulting data stream is processed by the left ventricular outflow tract assessment system.
  • the flow chart illustrates the possible inclusion of additional measurements and the use of volitional parameters as both an element of the configuration and included in every measurement or as additional elements if the measurement result has uncertainty and additional diagnostic information is desired.
  • FIG. 24 illustrates a simple pictorial diagram of the measurement configuration and the key elements of a Finger SPG measurement embodiment.
  • FIG. 25 illustrates the measurement configuration used for the illustrated embodiment.
  • the system uses speckle plethysmography as the measurement method to acquire an optical pulse plethysmogram with diminished sensitivity to vascular tone changes in the hand and the impact of vascular stiffness changes in the conduit arteries. Additional information including vital signs, demographics, and medications are included and used by the analysis system.
  • the pulse at the measurement site is enhanced by raising the arm above the heart, by having the patient in a supine position such that maximal filling of the heart occurs, and by having the measurement system exert additional external pressure at the measurement site, so transmural pressure is further reduced.
  • the sampling location is the finger, a readily accessible location requiring little operator expertise.
  • the resulting SPG measurement signal will be processed by the left ventricular outflow tract assessment system to determine abnormalities.
  • FIG. 26 illustrates a simple pictorial diagram of the measurement configuration and the key elements of an ear PPG measurement embodiment.
  • FIG. 27 illustrates the measurement configuration used for the illustrated embodiment.
  • the system uses photoplethysmography as the measurement method in the ear canal (2601) to acquire an optical pulse plethysmogram.
  • the ear represents a sampling location with minimal vascular tome changes. Additional information can include vital signs, demographics, and medications are included and used by the analysis system.
  • the measurement process shows a volitional activity requiring the patient to execute a breathing protocol with a resistance breathing device, 2602.
  • the breathing device uses a flow-independent pressure threshold valve on both inhalation and exhalation to create the square wave pattern shown.
  • a flow-independent pressure threshold valve is designed to provide consistent and specific pressure, regardless of how quickly or slowly patient breathes.
  • Threshold devices incorporate flow-independent one-way valves to provide consistent resistance and feature adjustable specific pressure settings.
  • the breathing device creates a constant intrathoracic pressure during these segments.
  • the resulting protocol or variances will alter the filling pressure to the heart in a deterministic fashion creating additional information for assessing left ventricular outflow tract abnormalities.
  • the pulse at the ear measurement site is enhanced by hydrostatic pressure decreasing the transmural pressure, will experience minimal changes in vascular tone, as is a sampling location rich with reflection information. The sampling location is the ear, readily accessible and requires little operator expertise.
  • the resulting PPG measured signal obtained during execution of the measurement protocol can be process by the left ventricular outflow tract assessment system in multiple ways. Specifically features can be extracted from the data stream or the totality of information used for analysis as a continuous data stream, or a combination of both.
  • the left ventricular outflow tract assessment system then provides a measurement result which could be a probability score associated with left ventricular outflow tract abnormality or a specific diagnosis and a severity score.
  • the above configuration is also suitable with modification for the sampling of the carotid artery.
  • the carotid arteries originate posterior to the sternoclavicular joints and in the neck and are contained within the carotid sheath posterior to the sternocleidomastoid muscle.
  • the arteries represent a sampling location that can be accessed by SPG or PPG using infrared light.
  • FIG. 29 illustrates a simple pictorial diagram of the measurement configuration and the key elements of an eye laser contrast speckle imaging embodiment.
  • FIG. 30 illustrates the measurement configuration used for the illustrated embodiment.
  • the system uses speckle imagining or ISPG (2901) in optical communication with the retinal as the measurement method to obtain an optical pulse plethysmogram based on blood flow in the fungus, which includes the retina, macula, fovea, and posterior pole.
  • the eye represents a location of stable vascular tone and is close to the heart. Additionally, the eye creates a unique optical access method such that larger arterial vessels can be sampled directly with a minimal scatter of the photons. Additional information can include vital signs, demographics, and medications and is used by the analysis system.
  • the measurement requires alignment of the optical system so the retina can be visualized as the patient remains still.
  • the pulse at the eye measurement site is enhanced by hydrostatic pressure decreasing the transmural pressure.
  • the sampling location is the eye which may require some specific operator training.
  • Speckle imaging allows for determining a pulse plethysmogram for a region of interest.
  • the region of interest can be a large area of the retina, freehand region of Interest (ROI), and cross-section of an artery or even a vein.
  • the resulting SPG measurement signal obtained during the execution of the measurement protocol can be processed by the left ventricular outflow tract assessment system in multiple ways. Specifically, features can be extracted from the data stream, or the totality of information used for analysis as a continuous data stream, or a combination of both. Additionally, the entire video image or a region of interest can be processed by the left ventricular outflow tract assessment system. The left ventricular outflow tract assessment system then provides measurement results which could be simply a probability score associated with a left ventricular outflow tract abnormality or a specific diagnosis and a severity score.
  • FIG. 31 illustrates a simple pictorial diagram of the measurement configuration and the key elements of a dual eye PPG imaging with ECG embodiment.
  • FIG. 32 illustrates the measurement configuration used for the illustrated embodiment.
  • FIG. 33 shows an example optical layout for creating optical communication with both eyes enabling a dual PPG or SPG sampling of the eyes.
  • the system uses photoplethysmography as the measurement method in the eye.
  • the eye represents a sampling location with minimal vascular tone changes. Additional information such as vital signs, demographics, and medications are included and used by the assessment system.
  • An EKG measurement, 3101 is also associated with the measurement to facilitate the calculation of pulse arrival time (PAT).
  • PAT pulse arrival time
  • the presence of aortic stenosis can cause variances in PAT between the right and left sides of the body.
  • the pulse at the eye measurement site is enhanced by hydrostatic pressure decreasing the transmural pressure.
  • the sampling system is located in a single headset, 3102, that creates a dark environment for pupil dilation and provide instructional information to the patient.
  • the PPG signals obtained from both eyes and the EKG information can be processed by the left ventricular outflow tract assessment system in multiple ways. Specifically, features can be extracted from the data stream or the totality of video information used for analysis as a continuous data stream, or a combination of both.
  • the left ventricular outflow tract assessment system then provides measurement results which could be a probability score associated with a left ventricular outflow tract abnormality or a specific diagnosis and a severity score.
  • FIG. 34 illustrates a simple pictorial diagram of the measurement configuration and the key elements of a chest PPG or SPG embodiment.
  • FIG. 35 illustrates the measurement configuration used for the illustrated embodiment.
  • the system uses photoplethysmography as the measurement method on the chest, 3401, to obtain an optical pulse plethysmogram.
  • the chest represents an optical sampling location with very little transit distance in the arteries from the heart. Additionally, the system can use an optical system of significant size and power consumption.
  • Such a measurement system could use a multi-detector, multi-source, and multi-wavelength configuration for the procurement of the best pulse waveform. As shown in Error!
  • the resulting PPG or SPG signals obtained from the chest will be processed by the left ventricular outflow tract assessment system in multiple ways. Specifically, features can be extracted from the data stream or the totality of video information used for analysis as a continuous data stream, or a combination of both.
  • the left ventricular outflow tract assessment system then provides a measurement result which could be simple a probability score associated with a left ventricular outflow tract abnormality or a specific diagnosis and a severity score.
  • FIG. 36 illustrates pictorially a speckle imaging application on the face of the patient.
  • PPG speckleplethysmographic
  • PPG photoplethysmographic
  • FIG. 36 illustrates a simple pictorial diagram of the measurement configuration and the key elements of the embodiment.
  • FIG. 37 illustrates the measurement configuration used for the illustrated embodiment.
  • the system uses speckle imaging as the measurement method on the face, by use of a camera or other optical system, 3701 .
  • the face is relatively close to the heart and is easily accessed for sampling. Additional information including vital signs, demographics, and medications are included and used by the analysis system.
  • the resulting SPG signals obtained from the face can be processed by the left ventricular outflow tract assessment system in multiple ways. Specifically, features can be extracted from the data stream or the totality of video information used for analysis as a continuous data stream, or a combination of both. T The left ventricular outflow tract assessment system then provides a measurement result which could be simple a probability score associated with a left ventricular outflow tract abnormality or a specific diagnosis and a severity score.
  • FIG. 37 is an illustration of this type of monitoring of two patients.
  • the Y-axis shows the estimated change in aortic valvular area from a baseline measurement taken between age 50-59.
  • the incidence of aortic stenosis is less than 0.5% in younger patients so it can serve as an effective baseline.
  • Eveborn, Gry Wisthus, et al. The evolving epidemiology of valvular aortic stenosis, the Tromso study.” Heart 99.6 (2013): 396-400.
  • Patient #1 has no evidence of aortic stenosis.
  • Patient #2 begins to develop stenosis with a significant decrease in aortic valve area.
  • the patient has a estimated aortic valve area of 50% the original baseline and has their valve replaced with a return to pre-stenosis function.
  • Additional Embodiments are contemplated as easily visualized in FIG. 39.
  • the figure illustrates that various combinations can be used to make determinations with respect to left ventricular outflow tract obstruction.
  • some configurations may be able to detect only the presence of an abnormality, while others may be able to deter the type and degree of obstruction present.
  • the measurement configuration presented are for illustrative purposes and can be tailored to meet user objective in terms of performance, expense and data acquisition difficulty.
  • a programmable apparatus can include one or more microprocessors, microcontrollers, embedded microcontrollers, programmable digital signal processors, programmable devices, programmable gate arrays, programmable array logic, memory devices, application specific integrated circuits, or the like, which can be suitably employed or configured to process computer program instructions, execute computer logic, store computer data, and so on.
  • a computer can include any and all suitable combinations of a special-purpose computer, programmable data processing apparatus, processor, processor architecture, and so on.
  • a computer can include a computer-readable storage medium that can be internal or external, removable and replaceable, or fixed.
  • Embodiments of the systems as described herein are not limited to applications involving conventional computer programs or programmable apparatuses that run them. It is contemplated, for example, that embodiments of the invention as claimed herein could include an optical computer, quantum computer, analog computer, or the like.
  • a computer program can be loaded onto a computer to produce a particular machine that can perform any and all of the depicted functions. This particular machine provides a means for carrying out any and all of the depicted functions.
  • Any combination of one or more computer readable medium(s) can be utilized.
  • the computer readable medium can be a computer readable signal medium or a computer readable storage medium.
  • a computer readable storage medium can be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing.
  • the computer readable storage medium includes the following: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing.
  • a computer readable storage medium can be any tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device.
  • Computer program instructions can be stored in a computer-readable memory capable of directing a computer or other programmable data processing apparatus to function in a particular manner.
  • the instructions stored in the computer-readable memory constitute an article of manufacture including computer-readable instructions for implementing any and all of the depicted functions.
  • a computer readable signal medium can include a propagated data signal with computer readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated signal can take any of a variety of forms, including, but not limited to, electro-magnetic, optical, or any suitable combination thereof.
  • a computer readable signal medium can be any computer readable medium that is not a computer readable storage medium and that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.
  • Program code embodied on a computer readable medium can be transmitted using any appropriate medium, including but not limited to wireless, wireline, optical fiber cable, RF, etc., or any suitable combination of the foregoing.
  • block diagrams and flowchart illustrations depict methods, apparatuses (i.e., systems), and computer program products.
  • Any and all such functions can be implemented by computer program instructions; by special-purpose, hardware-based computer systems; by combinations of special purpose hardware and computer instructions; by combinations of general purpose hardware specialized through computer instructions; and so on - any and all of which can be generally referred to herein as a "circuit,” "module,” or "system.”
  • each element in flowchart illustrations can depict a step, or group of steps, of a computer-implemented method. Further, each step can contain one or more sub-steps. For the purpose of illustration, these steps (as well as any and all other steps identified and described above) are presented in order. It will be understood that an embodiment can contain an alternate order of the steps adapted to a particular application of a technique disclosed herein. All such variations and modifications are intended to fall within the scope of this disclosure. The depiction and description of steps in any particular order is not intended to exclude embodiments having the steps in a different order, unless required by a particular application, explicitly stated, or otherwise clear from the context.

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Abstract

Des modes de réalisation de la présente invention fournissent une détermination fiable, pratique, rentable et non invasive d'anomalies structurales et valvulaires dans le tractus de sortie ventriculaire gauche. Des modes de réalisation permettent d'obtenir un pléthysmogramme d'impulsion optique non invasif à partir des phases systolique et diastolique du cycle cardiaque pour une analyse de forme d'onde morphologique ultérieure afin de déterminer des anomalies de tractus de sortie ventriculaire gauche. Les anomalies du tractus de sortie ventriculaire gauche modifient le taux d'augmentation de l'écoulement pendant la phase précoce de systole et le taux de diminution de l'écoulement pendant la phase tardive de systole. Ces variations d'écoulement au niveau de la valvule aortique sont amplifiées lorsque l'onde d'impulsion se déplace vers la périphérie en raison d'une association de l'interaction ventriculaire-aortique, de l'augmentation d'impulsion et des réflexions au niveau de vaisseaux de ramification et de changements de diamètre. Le système de test résultant peut être utilisé pour déterminer la présence d'anomalies et pour diagnostiquer le type d'anomalie.
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