Patient monitoring system using ultrasound and bioimpedance

Abstract

Patient monitoring for cardiophysiological function can include receiving an ultrasound waveform from a pulsed-wave ultrasound transducer array. The transducer array can be fixed externally on a patient to monitor a target vessel. Waveform fiducials can be identified from the ultrasound waveform indicating patient blood flow characteristics. Based on these fiducials, an ultrasound diagnostic indication of left ventricular ejection time (LVET) can be determined. A patient's cardiophysiological function can be assessed by combining the ultrasound diagnostic indication with bioimpedance cardiac waveform data.

Description

Docket No. 6582.001WO1 PATIENT MONITORING SYSTEM USING ULTRASOUND AND BIOIMPEDANCE CLAIM OF PRIORITY

[0001] This application claims priority to US provisional Application Serial No. 63 / 629,922, filed on December 14, 2023, which is incorporated by reference herein in its entirety, and the benefit of priority of which is claimed herein. BACKGROUND

[0002] Cardiac physiology monitoring can enable clinicians to assess various aspects of cardiovascular function through different measurement modalities. Ultrasound technology can provide certain information in medical diagnostics, such as to facilitate non-invasive visualization and measurement of internal patient anatomy. Similarly, bioimpedance cardiography can facilitate monitoring of cardiac function. BRIEF DESCRIPTION OF THE DRAWINGS

[0003] In the drawings, which are not necessarily drawn to scale, like numerals can describe similar components in different views. Like numerals having different letter suffixes can represent different instances of similar components. The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present document.

[0004] FIG. 1A is a block diagram for an example of portions of a system for patient monitoring using ultrasound and bioimpedance.

[0005] FIG. 1B is a flowchart showing an example of processing involving various sensors for patient monitoring using ultrasound and bioimpedance.

[0006] FIG. 1C is a chart showing an example of a Doppler ultrasound waveform indicating velocity of blood flow in vasculature over time.

[0007] FIG. 1D is a chart showing an example of a pulsed-wave (PW) spectral ultrasound waveform indicating velocity of blood flow in vasculature over time.Docket No. 6582.001WO1

[0008] FIG. 2A is a schematic diagram of an example of an ultrasonic transducer.

[0009] FIG. 2B depicts positioning of an ultrasonic probe toward a suprasternal notch of a human patient to facilitate sensing of a patient aorta.

[0010] FIG. 2C depicts an example of blood velocity directionality discrimination via an ultrasonic waveform.

[0011] FIG. 3A depicts an example of a pulsed-wave ultrasound transducer array.

[0012] FIG. 3B depicts an example of a pulsed-wave ultrasound transducer array.

[0013] FIG. 3C depicts an example of a pulsed-wave ultrasound transducer array.

[0014] FIG. 4A depicts an example of various sensors externally arranged on an adult patient for monitoring using ultrasound and bioimpedance.

[0015] FIG. 4B depicts an example of various sensors externally arranged on a neonate patient for monitoring using ultrasound and bioimpedance.

[0016] FIG. 5A is a chart showing an example of an ideal impedance cardiography waveform and a corresponding phonocardiographic (PCG) waveform over time.

[0017] FIG. 5B is a chart showing an example of an typical impedance cardiography waveform and a corresponding phonocardiographic (PCG) waveform over time.

[0018] FIG. 5C is a chart showing wall pressure, bioimpedance change curve (Zt), and impedance cardiography (ICG) waveforms corresponding with a carotid artery of a patient.

[0019] FIG. 5D is a chart showing a validated or adjusted bioimpedance cardiac waveform based on an ultrasound diagnostic indication as an input.

[0020] FIG. 6 is a chart showing ultrasound blood flow velocity time integrals for carotid artery and aorta during passive leg raise maneuver to assess fluid status.

[0021] FIG. 7 is a flowchart describing a process for deriving a cardiac output from patient carotid blood flow measured by an ultrasound waveform.Docket No. 6582.001WO1

[0022] FIG. 8 is a flowchart showing a process for patient monitoring using ultrasound and bioimpedance.

[0023] FIG. 9 is a block diagram of a machine. DETAILED DESCRIPTION

[0024] Several diseases and disorders can affect cardiac function and thus benefit from approaches to cardiac physiology monitoring. For example, these can include heart failure, kidney disease, fluid overload, sepsis, shock, and cardiorenal syndrome, such as in an adult, pediatric, or neonatal patients. Cardiorenal syndrome can be characterized as “any acute or chronic problem in the heart or kidneys that could result in an acute or chronic problem of the other.” For example, subtypes of cardio renal syndrome can include a sharp decline in cardiac function that results in an acute decrease in renal function, chronic cardiac dysfunction that results in a sustained reduction in renal function, a sharp decline in renal function that results in an acute reduction in cardiac function, a chronic decline in kidney function that results in chronic cardiac dysfunction, and systemic diseases that result in both cardiac and renal dysfunction. A prevalence of either cardiac or renal dysfunction is correlated with increased the incidence of the other.

[0025] Certain approaches to cardiac physiology monitoring, such as determining stroke volume (SV) or cardiac output (CO) include echocardiography, magnetic resonance angiography, thermodilution, arterial pressure line pulse contour analysis, impedance cardiography, non-invasive pulse contour analysis, among others. Such approaches introduce challenges of being invasive, expensive, time consuming, suffering from user variability, and being uncomfortable or unfeasible for certain patients (e.g., neonates). Bioimpedance cardiography is an approach for noninvasively monitoring cardiac function by measuring the electrical conductivity of thoracic tissue, which varies with blood volume changes during the cardiac cycle. Techniques for measuring bioimpedance can involve measuring bioreactance, single frequency impedance, multi-frequency impedance, or performing bioimpedance vector analysis. Such techniques can be implemented in thoracic impedance devices (e.g., including electrodes primarily placed on the thorax) or regional bioimpedance (e.g., including an electrode placed on theDocket No. 6582.001WO1 distal limbs). The aforementioned invasive and noninvasive approaches to cardiac physiology monitoring generally involve single-modality measurement or estimating of one or more indicators of cardiac function. For example, indicators of cardiac function can include SV, heart rate (HR), CO, respiratory rate, systemic vascular resistance, cardiac power, total body water, thoracic fluid content, left ventricular ejection time (LVET), and certain indicators can be interrelated. Such indicators of cardiac function can be used to help diagnose, monitor, and guide treatment for heart failure, kidney disease, cardiorenal syndrome, fluid overload, sepsis, shock, hypertension, pre-eclampsia, and many other disease states.

[0026] Certain noninvasive technologies (e.g., pulse contour analysis, certain approaches to bioimpedance cardiography, etc.), when performed alone can present challenges of undesirably low precision and accuracy. For example, certain bioimpedance based devices generally provide waveforms from patients exhibiting “noise” and other artifacts, which can be worsened based on patient-related factors such as obesity, edema, arrhythmias, patient motion artifacts, or variable skin / tissue moisture content. Certain bioimpedance approaches involve calculating CO or SV, in part, based on left ventricular ejection time (LVET). LVET, in such approaches, can be estimated from the impedance waveform based on identifying morphological landmarks or fiducials (e.g., a minimum point on the waveform). Noisy signals can confound an ability to reliably and consistently register systolic and diastolic time points in the cardiac cycle. Certain bioimpedance approaches can attempt to mitigate such challenges via signal processing (e.g., filtering) techniques to make the signal appear like its prototype thus helping in the correct identification of fiducials. However, such signal processing techniques alone can still result in significantly inaccurate or imprecise LVET estimation.

[0027] The present inventors have recognized the benefits of a technique for monitoring cardiophysiological function using a combination of ultrasound and bioimpedance technologies. The systems and methods described herein can utilize a pulsed-wave ultrasound transducer array that can be fixed at an external target body location of a patient to monitor blood flow in a target vessel. The transducer array can obtain ultrasound waveforms over a defined period, from which multiple waveform fiducials can be identified to provideDocket No. 6582.001WO1 detailed information about patient blood flow patterns. In an example, left ventricular ejection time (LVET) can be determined, e.g., based on the identified waveform fiducials from the ultrasound measurements. This ultrasound diagnostic indication can be used to inform bioimpedance cardiac waveform data, such as to provide a comprehensive assessment of the patient's cardiophysiological function.

[0028] For example, the system can be configured to receive bioimpedance cardiac waveform data over an extended period that encompasses the ultrasound measurement period. This allows for validation and adjustment of bioimpedance waveform fiducials based on time-corresponding ultrasound fiducials, enhancing measurement accuracy. In an example, a pulsed-wave ultrasound transducer array can be used to sense heart wall motion at a patient's suprasternal aortic notch. Here, the system can determine aortic diameter through imaging, and processes the ultrasound waveform to assess cardiac cycle characteristics based on calculated aortic area, independent of bioimpedance cardiography measurements.

[0029] The pulsed-wave ultrasound transducer array can include multiple elements that can be selectively energized to control the target region location (e.g., a depth and / or angle) for sensing. This can facilitate dynamic adjustment of the measurement focus by establishing or adjusting energy levels at different elements, such as to move between different target regions. In an example, the ultrasound transducer array can measure a vessel size by detecting a wall-to-wall region of blood flow via ultrasound pulses. The pulsed-wave ultrasound transducer array can include individual elements oriented in different directions for optimal monitoring of structures, such as a carotid artery of a patient. The ultrasound transducer array can include, e.g., non-imaging Doppler or non-imaging ultrasound technology. The pulsed- wave ultrasound transducer array can additionally or alternatively include one or more specialized configurations such as a concentric, circular array surrounding a rectangular matrix. In an example, in addition to the pulsed- wave ultrasound transducer array, the system can also include at least one continuous wave ultrasound transducer, e.g., to provide sensing at relatively higher maximum blood velocities as compared to the pulsed-wave ultrasound transducer array.Docket No. 6582.001WO1

[0030] In an example, the system can include or use each of a phonocardiogram, a pulsed-wave ultrasound transducer array, and a bioimpedance electrode. Such a multimodal system can rely entirely on noninvasive sensors and can combine at least two of an ultrasound waveform, a bioimpedance waveform, and an electrocardiogram (ECG) waveform, such as to create a composite measurement of systolic and diastolic time intervals, fiducials, heart valve status, SV, CO, or one or more other derived parameters. The at least two waveforms can be time-synchronized, such as to help ensure correlation with respect to important morphological landmarks and fiducials validated by each of the two waveforms. In certain instances, each of the ultrasound waveform, the bioimpedance waveform, and the ECG waveform can be monitored, time-correlated, and used to recurrently or continuously validate, correct, or calibrate one another. Such a multimodality system can leverage respective advantages of each type of waveform to achieve an accuracy of precision of composite measurement of cardiac fiducials, which can be used to calculate and monitor SV, CO, and other indicators of cardiophysiological function.

[0031] FIG. 1A is a block diagram for a system for patient monitoring using ultrasound and bioimpedance. A patient monitoring system 100 for assessing cardiophysiological function can include a monitoring unit 102, processing circuitry 104, a bioreactance impedance cardiograph 114, and an ultrasound receiver 116. The monitoring unit 102 can receive an output from a plurality of non-invasive sensors, configured to be worn on external target body location of a human patient (e.g., a bioimpedance electrode 108, a pulsed- wave ultrasound transducer 110, or a microphone 106). The system 100 can monitor at least two of an ultrasound waveform, a bioimpedance waveform, and an ECG waveform from the non-invasive sensors over time, and determine a composite measurement based on the at least two waveforms indicative of a cardiophysiological function of the patient without a need for invasive sensing such as from a catheter (such as an esophageal bioimpedance catheter, esophageal ultrasound / doppler catheter, etc.), insertion probe, or any device configured for invasively measuring arterial blood pressure (ABP) (such as an intraarterial probe). In an example, the system 100 can determineDocket No. 6582.001WO1 the composite measurement without a need for auxiliary sensing via pulse oximetry or impedance obtained from the peripheral vasculature of the patient.

[0032] The pulsed-wave ultrasound transducer 110 can be configured to be fixed at a first external target body location of the patient. For example, the pulsed-wave ultrasound transducer 110 can be externally positioned to monitor a patient vessel and can provide ultrasound waveform data over a first time period to processing circuitry 104. The processing circuitry 104 can identify a plurality of fiducials from the received ultrasound waveform, with at least one fiducial of the plurality providing specific information about one or more patient blood flow characteristics. For example, the at least one fiducial can indicate a start of systole, an end of systole, or an amplitude during LVET. Based on these identified fiducials, the processing circuitry 104 can determine an ultrasound diagnostic indication of left ventricular ejection time (LVET). As explained further below, the processing circuitry 104 can also combine this indication of LVET with bioimpedance cardiac waveform data, e.g., to generate an overall indication of the patient's cardiophysiological function.

[0033] In an example, the pulsed-wave ultrasound transducer 110 can be a transducer array including a plurality of individually controllable elements such as piezoelectric crystals. These elements can be selectively energized (e.g., via a control signal from the processing circuitry 104) to control the target region location, depth, or angle of patient tissue for sensing. For example, the pulsed-wave ultrasound transducer 110 can module a depth of the target region location based on ultrasonic wave travel time. In an example, the processing circuitry 104 can adjust energy levels at different elements to move the measurement focus between different target regions, such as to measure a vessel size by sensing wall-to-wall blood flow for the vessel. Individual elements within the array can be oriented in different directions, the directionality configured for monitoring a relatively fine structure such as a patient carotid artery from the external target body location. The array can implement, e.g., non-imaging Doppler or non-imaging ultrasound elements. In an example, the system 100 can include a continuous-wave ultrasound transducer 144, configured to provide additional ultrasound waveform data over the first period, offering capability to sense higher maximum bloodDocket No. 6582.001WO1 velocities than the via pulsed-wave ultrasound transducer 110 alone. By contrast to the pulsed-wave ultrasound transducer 110,, the depth for a continuous-wave ultrasound transducer 144 can be controlled or set based on an angulation of individual transducer elements or crystals.

[0034] The pulsed-wave ultrasound transducer 110, the continuous-wave ultrasound transducer 144 can, or both can be communicatively coupled with the ultrasound receiver 116. In an example, the ultrasound receiver 116 can include an ultrasound flow meter configured to determine blood flow velocity information (as a component of waveform information more generally). In an example, the ultrasound receiver 116 can be configured to provide ultrasonic data such as M-mode ultrasonic echocardiography, pulsed-wave (PW) Doppler ultrasonography, or color-flow ultrasonography. Data from the ultrasound receiver 116 can be captured digitally by the system 100 (e.g., as a digital audio signal). In an example, the data can be broadcast via a transceiver 118 or alternatively directly by the ultrasound receiver 116 for remote digital analysis, such as by a distant location processing unit or a computing cloud.

[0035] The system 100 can include at least two bioimpedance electrodes 108 that can be fixed on the human patient at a second external target body location. This bioimpedance electrode 108 can provide bioimpedance cardiac waveform data corresponding to the patient vessel over a second time period. For example, the second time period can be longer than and encompass the first period of ultrasound monitoring, such as where ultrasonic sensing is performed at intervals during continuous bioimpedance sensing. The processing circuitry 104 can use time-corresponding ultrasound waveform fiducials to validate or adjust the bioimpedance waveform fiducials, such as to calibrate the bioimpedance waveform or to determine a composite measurement of LVET, CO, SV, or another parameter. In an example, the bioimpedance electrode 108 can be communicatively coupled with the bioreactance impedance cardiograph 114. The bioreactance impedance cardiograph 114 componentry can include an analog-to-digital converter (ADC) and a processor (e.g., a digital signal processor) configured to estimate the bioimpedance waveform fiducials.Docket No. 6582.001WO1

[0036] In an example, the system 100 can include or use an imager 142 configured to provide imaging data of internal patient anatomy when positioned at or near the first external target location. Such auxiliary imaging can help facilitate sensing a vessel wall property (e.g., vessel wall motion or aortic diameter), e.g., at a suprasternal aortic notch or other target vessel, via the pulsed-wave ultrasound transducer 110. For example, such auxiliary imaging can involve determining aortic diameter via A-mode scanning or B- mode scanning. The processing circuitry 104 can receive the imaging data and the non-imaging ultrasound waveforms, calculate aortic area, and can determine cardiac cycle characteristics independent of the bioimpedance measurements.

[0037] In an example, the system 100 can include a user interface 122 configured displaying cardiac output indicators and other diagnostic information. The user interface 122 can be a graphical display formatted for usability and data access by a human user. In an example, the user interface 122 can convey certain information such as a series of alphanumeric reports, including indicia (such as waveforms, plots, tables, bars, histograms, pie charts, illustrations, animations, or numeric fields), conveying clinical outcomes to report altogether at different detection times (corresponding to an ultrasound detection or a bioimpedance detection). Such a presentation can relate to, e.g., direct cardiac function assessments, non-cardiac / cardiac outcomes over time, or historical procedure outcomes. Input by the user can be received by user interface 122 for use by system 100 such as to initiate or continue performing diagnostic monitoring in certain contexts, such as surgery procedures or rehabilitation procedures. In an example, information from the patient or bioimpedance and ultrasound devices can be presented via the user interface 122 in real time (e.g., concurrently with receiving the ultrasound waveform or the bioimpedance waveform) to facilitate monitoring a clinical procedure.

[0038] Optionally, the system 100 can include or use the phonocardiogram 112 and the microphone 106. As described further with respect to FIG. 6, the microphone 106 can be placed on the patient to record a PCGs signal, e.g., to capture heart sounds from the patient corresponding with specified waveform fiducials. The microphone 106 can be a microphone chip, diaphragmDocket No. 6582.001WO1 microphone, capacitive microphone, piezoelectric microphone, optoelectric (fiber optic) microphone, or any other capacitive-type microphone. The phonocardiogram 112 can include an ADC and a processor configured to identify specified sound patterns such as a systolic or a diastolic murmur rule for cardiac sound detection.

[0039] FIG. 1B is a flowchart showing an example of processing involving various sensors for patient monitoring using ultrasound and bioimpedance. The system 100 can receive one or more of an ICG signal 124, a PCG signal 128, a doppler / ultrasound signal 130, or an ECG signal 126, and the processing circuitry 104 can process the one or more signals via respective operations 132, 134, and 138 or filtering 136 to determine a composite measurement of cardiac fiducials 140.

[0040] The following equations and derivations demonstrate the correspondence between changes in electrical impedance in the thorax or body generally to volumetric changes (e.g., cardiac output, stroke volume, or the like). In an example, the processing circuitry 104 can include instructions that when executed by a processor, cause the processor to perform one or more of below Equations 1-27 (e.g., as a part of an algorithm to calculate the composite measurement 140) and likewise any of Equations 28-32 described with respect to FIG. 2A.

[0041] Equation 1 includes total body impedance (Zt), impedance of the thorax (Zth), and impedance of the blood of the patient (Zb):

[0042] Equation

[0043] Equation 2 defines the impedance of the body other than the thorax(Zb). Equation 2 includes the resistivity of blood ( ), length of the body (l),and area of the body other than thorax (Ab). In some examples, the system 100can monitor changes in the resistivity of blood ( ) based on changes in thetotal body impedance (Zb).

[0044] Equation

[0045] Equation 3 defines the volume of the body of the patient (Vb).

[0046] EquationDocket No. 6582.001WO1

[0047] Equation 4 is the partial derivative of Zt with respect to Zb. Algebraically manipulating Equation 4 yields Equation 5.

[0048] Equation

[0049] Equation

[0050] Equation 6 includes algebraically manipulating Equation 2 and substituting the algebraically manipulated Equation 2 into Equation 3.

[0051] Equation

[0052] Equation 7 is the partial derivative of Vb with respect to Zb.

[0053] Equation

[0054] Equation 8 multiplies Equation 7 and Equation 5. Algebraically manipulating Equation 8 yields Equation 9. Additionally, algebraically manipulating Equation 9 yields Equation 10.

[0055] Equation

[0056] Equation

[0057] Equation

[0058] Equation 11 includes algebraically manipulating Equation 10 and taking the partial derivative of Vb with respect to time (t).

[0060] Accordingly, Equation 11 describes a change in volume with respect to time. Applying Equation 11 to an aorta of a patient yields Equation 12. Equation 12 describes the volume of blood pumped into the aorta of the patient with each heartbeat of the patient. In another example, Equation 12 describes the stroke volume of the patient.

[0061] Equation 12:Docket No. 6582.001WO1

[0062] Equation 12 includes a duration of ventricular ejection (tejection). In another example, tejection corresponds with the left ventricular ejection time (LVET). Accordingly, Equation 13 substitutes LVET for tejection in Equation 12. In an example, as explained further below with respect to FIG. 5C and 5D,( *l2) ÷ ((Zt)2) of Equation 12 can be treated as a constant (k) which can beloosely related to a particular patient’s height, weight, sex, age, or BMI. As explained below, devices and systems described herein can actually measure“k” (i.e., ( *l2) ÷ ((Zt)2)), rather than relying on estimates based on patientinformation.

[0063] Equation 13:

[0064] Equation 13 shows the physiological parameters that affect stroke volume (SV) using the ICG signal 124. For example, the LVET can have a direct proportional effect on the SV (e.g., calculated by the processing circuitry 104).

[0065] Equation 14 defines the cardiac output of the patient. The cardiac output of the patient is equal to the stroke volume of the patient multiplied by the heart rate of the patient.

[0066] Equation 14:

[0067] In an example, the system 100 can use the ICG signal 124 to determine a heart rate of the patient. Accordingly, the processing circuitry 104 can receive a signal from the bioreactance impedance cardiograph 114 or the bioimpedance electrode 108, such as to determine the cardiac output of the patient. For instance, the bioreactance impedance cardiograph 114 can monitor one or more of the baseline total body impedance (Zt), the bloodresistivity ( ), or the heart rate of the patient using the bioimpedanceelectrode 108. The processing circuitry 104 can use monitored physiological parameters to determine the cardiac output of the patient. The processing circuitry 104 can improve an accuracy of the cardiac output determination by monitoring one or more of the baseline total body impedance (Zt), the bloodresistivity ( ), or the heart rate of the patient.

[0068] The system 100 can determine the ejection time (or LVET) at least in part using the ICG signal 124. Alternatively or additionally, the system 100Docket No. 6582.001WO1 can receive a doppler / ultrasound signal 130 from the pulsed-wave ultrasound transducer 110 and use the signal 130 to determine, at least in part, the LVET of the patient. In an example, determining the LVET including using the doppler / ultrasound signal 130 can be more accurate than determining the ejection time using the ICG signal 124 alone. For example, the processing circuitry 104 can determine the LVET based on a monitored velocity of blood flow in the carotid artery. Here, the processing circuitry 104 can identify a first heart sound (S1) of the patient using the pulsed-wave ultrasound transducer 110. The first heart sound (S1) can, e.g., correspond with closure of mitral and tricuspid valves (e.g., associated with the start of systole). The processing circuitry 104 can also identify a second heart sound (S2) of the patient using the pulsed-wave ultrasound transducer 110, S2 corresponding with a closure of the aortic and pulmonic valves (e.g., associated with the end of systole). In an example, the processing circuitry 104 can calibrate, validate, or adjust a timing of S1 or S2 based on the PCG signal 128, such as to compensate for a time delay of monitoring cardiac events at or near the aorta or carotid artery and via the pulsed-wave ultrasound transducer 110. In an example, the LVET can be calculated by the processing circuitry 104 based on a difference between the first heart sound (S1) and the second heart sound (S2).

[0069] Figure 1C shows an example of a velocity waveform corresponding to the monitored velocity of blood flow in vasculature, e.g., velocity of blood flow in a carotid artery of a patient. FIG. 1D shows a similar example of a velocity waveform, received from a spectral ultrasound transducer and over several cardiac cycles. The doppler / ultrasound 130 from the pulsed-wave ultrasound transducer 110 can be used by the processing circuitry 104 to determine the velocity of blood flow in the carotid artery. In an example, the processing circuitry 104 can identify one or more inflection points (e.g., peak systole, dicrotic notch, etc.) in the velocity waveform corresponding to a specified heart sound of the patient. For example, the inflection points can include one or more of a change in magnitude of a derivative of the velocity waveform, such as an increase in the rate that the slope is decreasing a change in sign of the slope of the velocity waveform a change in sign of the derivative of velocity waveform, peaks and valleys, etc.Docket No. 6582.001WO1

[0070] In an example, the processing circuitry 104 can determine physiological parameters of the patient, such as cardiac power of the patient. Generally, the cardiac power of the patient can equal the cardiac output of the patient multiplied by the mean arterial pressure of the patient. Here, the mean arterial pressure can be determined be based on an indication of systolic pressure and an indication of diastolic pressure of a patient, e.g., determined based on the ICG signal 124, the ECG signal 126, the 128, or the doppler / ultrasound signal 130.

[0071] Equation 15 defines an approach to calculating mean arterial pressure (MAP).

[0072] Equation 15:

[0073] Equation 16 defines another approach to calculating MAP, such as in an adult patient, based on diastolic pressure (DBP) and pulse pressure (PP).

[0074] Equation 16:

[0075] Equation 17 defines a similar approach to calculating MAP, such as in a pediatric patient.

[0076] Equation 17:

[0077] Equation 18 defines a similar approach to calculating MAP, such as in a neonate patient.

[0078] Equation 18:

[0079] Alternatively or additionally, during receiving information related to the neonate’s radial arterial line, mean arterial pressure can be approximated by averaging the systolic and diastolic blood pressure.

[0080] Equation 20 defines an approach to estimating systemic vascular resistance (SVR).

[0081] Equation 20:

[0082] Certain single-modality bioimpedance systems rely on an assumed value for central venous pressure (CVP). This can present challenges in accurately estimating SVR, as CVP can significantly vary from patient to patient and can be, e.g., elevated based on a disease state. In an example, the system 100 can facilitate measuring CVP rather than assume CVP based onDocket No. 6582.001WO1 other patient data (e.g., height, weight, age, sex, BMI, etc.). In an example, the ultrasound receiver 116 can receive an input from a cuff, configured to be wrapped around a patient limb, the cuff including a distal Doppler transducer configured to measure venous pressure in the arm (PVP) in a similar manner to measurement of arterial pressure. For example, the cuff can be inflated until the ultrasound receiver 116 determines that a Doppler flow signal from the cuff is obliterated, and subsequently the cuff can be deflated until venous Doppler signal re-emerges. Alternatively or additionally, the ultrasound receiver 116 can receive either a pulsed-wave or continuous wave ultrasound signal from an auxiliary ultrasound transducer placed at or near a patient cubital fossa. Here, an arm cuff can be applied to the patient, and the 116 can facilitate measurement of peripheral venous pressure via the ultrasound signal from the auxiliary ultrasound transducer to record obliteration of the signal during cuff inflation and return of signal during cuff deflation. In an example, the processing circuitry 104 or an operator can trigger such a measurement of CVP periodically (e.g., during the second period of continuous bioimpedance sensing) to continually reinform the system 100.

[0083] Figure 2B shows a schematic diagram of an example of an ultrasonic transducer. Details discussed below with respect to the exemplary ultrasonic transducer 212 can similarly apply to the pulsed-wave ultrasound transducer 110 and continuous-wave ultrasound transducer 144 of FIG. 1A. In an example, the ultrasonic transducer 212 includes a transmitter 202 and a receiver 204. The transmitter 202 can generate a signal, such as an ultrasonic wave, and transmits the signal through the blood in a patient vessel. The signal is scattered by constituents of the blood, and the scattered signal can be received (e.g., by the receiver 204). The ultrasonic transducer 212 can determine the velocity of the red blood cell 200 using the scattered signal received by the receiver 204. In an example such as in the case of a pulsed- wave ultrasonic transducer (e.g., the pulsed-wave ultrasound transducer 110), a single element (e.g., element 202) can both transmit and receive ultrasonic wave pulses to similarly determine the velocity of the red blood cell 200. As further discussed below with respect to FIG. 3A, FIG. 3B, and FIG. 3C, a “focal point” 206 of such an ultrasound transducer 212 can be adjusted viaDocket No. 6582.001WO1 phase modulation or ultrasonic crystal multiplexing such as focus the ultrasound waveform on a target vessel.

[0084] The velocity of the red blood cell 200 flowing through a vessel 201 can be determined according to the following equations including the variables: velocity of the red blood cell 200 (v), speed of sound in blood (c), the frequency of the signal transmitted by the transmitter 202 (fo), the Doppler shifted frequency of the signal transmitted by the transmitter 202 (f’), the angle between a longitudinal axis of the vessel 201 and the transducer The Doppler shift frequency (fd) can be equal to the difference between fo and f’. Equation 21 is the Doppler shift equation and includes the following variables: the velocity of sound (Vc), velocity of observer (Vob), and the velocity of source of emitted sound waves (Vs).

[0086] Applying Equation 22 to the ultrasonic transducer 1512 and the red blood cell 200 yields Equation 22:

[0087] Equation 22:

[0088]

[0089] Equation 23:

[0090] Equation 24:

[0091] Substituting Equations 23 and 24 into Equation 22 yields Equation 25:

[0092] Equation 25:

[0093] As described herein, the Doppler shift frequency (fd) is equal to the difference between fo and f’:

[0095] Substituting Equation 25 into Equation 26 yields Equation 27:

[0096] Equation 27:Docket No. 6582.001WO1

[0097] Algebraically manipulating Equation 27 yields Equation 28:

[0098] Equation 28:

[0099] Equation 28 may be algebraically manipulated to yield Equation 29:

[0100] Equation 29:

[0101] Algebraically manipulating Equation 29 yields Equation 30:

[0102] Equation 30:

[0103]

[0104] Equation 31:

[0105] Equation 31 may be algebraically manipulated to determine the velocity of the red blood cell 200 (v) in Equation 32:

[0106] Equation 32:

[0107] FIG. 2B depicts a manual positioning of an ultrasonic probe toward a suprasternal notch of a human patient to facilitate sensing of a patient aorta. FIG. 2C depicts an example of blood velocity directionality discrimination via an ultrasonic waveform. As depicted in FIG. 2B, an ultrasound transducer (e.g., the pulsed-wave ultrasound transducer 110 of FIG. 1A) can be placed at an external target body location of a patient to examine at least one of a carotid artery or an aorta of the patient. Generally, due to the proximity of the central aorta and the carotid circulation, there is no significant difference between central aortic and carotid artery pressures. Thus herein, certain techniques regarding ultrasonic sensing of the aorta (e.g., at the suprasternal notch as shown in FIG. 2C) can similarly apply to ultrasonic sensing at the carotid artery. Here, the Doppler shift frequency (fd) can be equal to the difference between fTand fR. Based on whether a positive or negative shift is detected, a directionality of blood flow can be determined.

[0108] FIG. 3A, FIG. 3B, and FIG. 3C each depict an example (110A, 110B, 110C, respectively) of a pulsed-wave ultrasound transducer array. One or more of these transducer arrays, 110A, 110B, 110C can be used with theDocket No. 6582.001WO1 system 100 as described in FIG. 1A. Each of the transducer arrays 110A, 110B, 110C include a plurality of elements 350, collectively arranged to provide control of a specified target region location at which the ultrasound waveform is sensing. In an example, each element 350 is a discrete piezoelectric crystal or other ceramic material with piezoelectric properties.

[0109] As depicted in FIG. 3A, the pulsed-wave ultrasound transducer array 110A can include a plurality of element 350 arranged in a grid and oriented in multiple directions with respect to one another. Here, the pulsed-wave ultrasound transducer array 110A can be formed on a wearable adhesive patch, such that it can be e.g., attached directly to patient skin on a patient neck. In an example, each element 350 in the pulsed-wave ultrasound transducer 110 can be communicatively coupled with a multiplexer (e.g., on a printed circuit board (PCB) included in the pulsed-wave ultrasound transducer 110A or included in the ultrasound receiver 116), and the multiplexer can select one or more of the element 350 to control a spatial position where the ultrasound waveform is focused. For example, the multiplexer can modulate activation of the elements 350 in order to search for a viable signal from a target vessel. Such an automatic focusing of a pulsed-wave ultrasound signal can limit a need to manual reposition the pulsed-wave ultrasound transducer array 110A and can facilitate capturing an optimized ultrasound signal at the target vessel. In an example, the pulsed-wave ultrasound transducer array 110A can include at least 12 elements 350, such as at least 20 elements 350, such as at least 30 elements 350, such as at least 25 elements 350, such as at least 50 elements 350, such as at least 100 elements 350, such as at least 200 elements 350, such as at least 500 elements 350. In an example, each element 350 of the plurality of elements can be oriented in a different direction than one another. In an example, the pulsed-wave ultrasound transducer 110 can be used by the processing circuitry 104 (as depicted in FIG. 1A) to measure a diameter of the target vessel. For example, the elements 350 can be controllably activated (e.g., multiplexed) such as to measure a wall-to-wall area where flow is present, and from that measurement the vessel diameter can be derived. Such a measurement of vessel diameter via wall tracking can provide a more accurate measurement of flow rate through the vessel as compared with otherDocket No. 6582.001WO1 approaches that estimate vessel diameter based on height, weight, BMI, sex, or age of the patient.

[0110] FIG. 3B and FIG. 3C each provide alternative orientations of a plurality of elements 350 of a transducer array. For example, in FIG. 3B, the elements 350 can form an annular array of concentric rings. Such rings can exhibit a time delay with respect to one another, and the rings can be multiplexed such as to control a focal depth of the beam which can be adjusted electronically (e.g., via the ultrasound receiver 116 or the processing circuitry 104 as depicted in FIG. 1A). The orientation of elements 350 shown in FIG. 3C can provide a similar level of control, as the elements 350 are arrange in a concentric array surrounding a small rectangular matrix. Such an orientation can facilitate capturing a useful ultrasound signal of the target vessel regardless of an orientation of the pulsed-wave ultrasound transducer array 110B as a whole. Such a level of electronic control can limit an amount that a user must manually adjust a position of the 110B.

[0111] Additional techniques for controlling activation of the elements 350 of arrays 110A, 110B, and 110C can be performed to facilitate ultrasonic “searching” across different depths in the patient tissue. For example, such techniques can involve a measurement of ultrasonic wave travel time. In an example, the relationship of “wait time” of a pulsed ultrasound signal to tissue depth is about 13 microseconds per centimeter (µsec / cm). Further, controlling a signal phase of individual elements 350, can provide an ability to steer a focus of the ultrasound waveform toward a target vessel. In an example, the processing circuitry 104 can measure a plurality signals over time, each signal corresponding with a different element 350, and algorithmically pick or average from these signals such as to help determine LVET or using a correlation function to select from the signals for a viable signal, such as by looking for a time-synchronization between bioimpedance and ultrasonic signals.

[0112] FIG. 4A and FIG. 4B each depicts an example of various sensors externally arranged on a patient for monitoring using ultrasound and bioimpedance. In an example, the system 100 (as depicted in FIG. 1A) can include or use a plurality of impedance electrodes, including located at two orDocket No. 6582.001WO1 more of a patient forehead (bioimpedance electrode 108A), a base of a patient neck (bioimpedance electrode 108B), a left or right side of center on soft tissue at or near the patient clavicle (bioimpedance electrode 108C), or on an upper torso of the patient at or near a bottom of a patient sternum, or on a lower torso at or near iliac crest (bioimpedance electrode 108D). Here, the pulsed-wave ultrasound transducer array 110A can be an adhesive patch configured to be placed on a patient neck and adhering directly to patient skin. With regard to certain neonate patients (e.g., the patient depicted in FIG. 4B), a top bioimpedance electrode 108A can be placed on the forehead (as depicted) or rather on a patient neck, such that at least two bioimpedance electrodes are located at the neonate patient neck.

[0113] Optionally, the system 100 can include or use the microphone 106 to provide an ICG signal 124 (as shown in FIG. 1B), such as place at or near a patient thorax to identify cardiac cycle events (e.g. aortic valve closure). In an example, the ICG signal 124 can be used by the system 100 to help identify accurate fiducials in the presence of interfering, other signals. In an example, an ultrasonic signal (e.g., from the pulsed-wave ultrasound transducer array 110A or the continuous-wave ultrasound transducer 144) can be used to help a healthcare provider to properly place the microphone 106 to provide a desired, viable ICG signal 124. Here, once the system 100 can determine a reliable ultrasonic signal from at least one of the carotid artery or the aorta and use that signal as a reference for cardiac cycle events. In an example, the provider can be directed, via the reliable ultrasound signal, as to manually positioning the surface microphone 106 until it is placed in a location for providing a desired ICG signal 124.

[0114] FIG. 5A and FIG. 5B are each charts showing an example of an impedance cardiography waveform and a corresponding phonocardiographic (PCG) waveform over time. FIG. 5C is a chart showing wall pressure, bioimpedance change curve (Zt), and impedance cardiography (ICG) waveforms corresponding with a carotid artery of a patient. FIG. 5D is a chart showing a validated or adjusted bioimpedance cardiac waveform (bottom) based on an ultrasound diagnostic indication (e.g., Paorta) as an input.Docket No. 6582.001WO1

[0115] In an example, as shown in FIG. 5A, the system 100 (as shown in FIG 1A) can include or use a phonocardiogram (PCG) signal 512 to help identify the timing of heart valve closures (e.g., S1 and S2), such as to help calibrate, adjust, or validate a time-corresponding fiducial of a bioimpedance signal 510 or an ultrasound signal. While FIG. 5A depicts an “ideal” capture of a bioimpedance signal 510, FIG. 5B depicts a more typical capture of the bioimpedance signal 510 in operation and use, which can present challenges to hemodynamic assessment due to signal artifacts and noise.

[0116] In a similar fashion, as shown in FIG. 5C, the system 100 can calculate, based on a doppler / ultrasound signal 130 (as shown in FIG. 1B) a wall pressure over time (Paorta) to help calibrate, adjust, or validate a time- corresponding fiducial the ICG signal 124. With specific regard to FIG. 5C and FIG. 5D, an ultrasound velocity waveform (such as carotid or aortic velocity waveform) which is received from a pulsed-wave ultrasound transducer can provide a reliable, repeatable measurement which can be used to correct the ICG signal 124, which can be vulnerable to noise or artifacts introduced by patient motion (e.g., as shown in FIG. 5B). Such an advantage of the doppler / ultrasound signal 130, over the ICG signal 124, can be used to periodically correct inaccuracies of the ICG signal 124 and thus to better identify LVET. In obtaining a more accurate and precise measure for LVET, the system 100 can likewise calculate stroke volume (SV) and cardiac output (CO). Further, the doppler / ultrasound signal 130 or a derivative thereof (e.g., a wall tracking waveform such as Paorta) can also be used to identify a start and an end of ventricular ejection in a way that is superior to doing so strictly from the ICG waveform.

[0117] In an example, (as related to Equation 12, above), a formula forcalculating LVET can involve a parameter “k” (i.e., ( *l2) ÷ ((Zt)2)), whichcan be assumed to be constant. Generally, other approaches to measuring LVET using only bioimpedance can involve estimating “k”, such as based on a particular patient’s characteristics such as height, weight, age, sex, or BMI. The present devices and methods can involve independent measurement of“k” (i.e.,For example, independent measurement of “k”can involve measuring cardiac output (CO) in a patient aorta via a pulsed- wave ultrasound transducer. A heart rate (HR) can also be concurrentlyDocket No. 6582.001WO1 measured, and the CO can be divided by the HR to calculate stroke volume (SV)ultrasound. In an example, the (SV)ultrasound can be compared with a stroke volume calculated by bioimedance, “(SV)bioimpedance”, an “k” can be derived from the comparison. Such an independent measurement of “k” is distinct from certain other bioimpedance devices, and can be used for more accurate patient hemodynamic assessment, particularly in neonate patients for which “k” can not be as-accurately estimated.

[0118] In an example, the system 100 can calculate an O / C ratio based on the various signals represented in FIG. 5A, FIG. 5B, FIG. 5C, and FIG. 5D the O / C ratio defined as the amplitude of the impedance cardiogram during diastole (O) divided by the maximum height during systole (C). Such an O / C ratio can exhibit a significant correlation with, and serve as a proxy indication of, pulmonary capillary wedge pressure (PCWP) which is generally only directly measured using invasive techniques.

[0119] FIG. 6 is a chart showing ultrasound blood flow velocity time integrals for carotid artery and aorta during passive leg raise maneuver to assess fluid status. In an example, the processing circuitry 104 (as depicted in FIG. 1A) can include calibration functionality that compares ultrasound and bioimpedance measurements with each other, following physical stimuli such as a passive leg raise (PLR), to facilitate optimization of measurement accuracy across both ultrasound and bioimpedance monitoring modalities. For example, a calibration approach can involve a straight comparison and adjustment between an ultrasonic measurement of flow against a time- correlated bioimpedance measurement of flow, such as at a baseline and after a physical stimulus (e.g., PLR).

[0120] FIG. 7 is a flowchart describing a process for deriving a cardiac output from patient carotid blood flow measured by an ultrasound waveform. In an example, the system 100 (as depicted in FIG. 1A) can predict cardiac output (CO) solely based on a carotid artery flow determined via an ultrasound signal. Such a projected CO can subsequently be used, e.g., for the calibration of an ICG signal.

[0121] For example, in adults normal typical cerebral blood flow (e.g., for carotid arteries and basilar arteries) is about 15-16%. In pediatric andDocket No. 6582.001WO1 neonates, cerebral blood flow can vary over a wide range of ages, particularlyup to about 50% in newborns. The flow can be divided into the anteriorcirculations (carotid arteries) and posterior circulations (basilar) arteries. There exists a relationship of about 30% of the 16% (resulting in about 5%)of cardiac output that is the flow in one carotid in adults. The age varyingcerebral blood flow percent of cardiac output in pediatric and neonatal patients is about 30% on average, and 30% of the 30% (resulting in about 9%) of cardiac output that is the flow in one carotid in pediatric patients (>1 year old) and 30% of the 50% (resulting in about 15%) of cardiac output that is the flow in one carotid in newborns.

[0122] Such a relationship for the single carotid artery can be represented byseveral equations, listed below.

[0123] Equation 33 is a Dubois formula for calculating body surface area(BSA).

[0124] Equation 33:

[0125] Any individual’s cardiac output is dependent upon their metabolicrate. The metabolic rate is directly related to the BSA. Alternatively oradditionally a formula for calculating BSA in adults and non-infant pediatrics is the Mosteller formula. For example, BSA is about 1.9 m2for the normal 30 year old 70 kg adult male.

[0126] Equation 34 is the Mosteller formula for calculating BSA.

[0127] Equation 34:

[0128] Equation 35 is a Meban formula for calculating BSA, particularly innewborns.

[0129] Equation 35:

[0130]

[0131] Equation 36 shows how a normal cardiac index, based on BSA, canbe calculated, assuming an adult with a VO2 of 126 mL O2 / min / m2, Hb of 15g / dL, SaO2 of 99%, and SvO2 of 75.Docket No. 6582.001WO1

[0132] Equation 36:

[0133] Equation 37 shows a VO2 normalized for BSA, the cardiac index (CI).

[0134] Equation 37:

[0135] Unlike in the adult and pediatric patient, where CO is normalized forBSA, cardiac output in neonates can be normalized instead based on bodymass or weight. Cerebral blood flow can be tightly autoregulated over most ofblood pressure ranges with some influence by carbon dioxide and oxygen levels and their impacts on vascular reactivity. However, cardiac output canalso be well controlled over most of the range of blood pressure. Other thanacute and temporary changes in arterial pressure, blood pressure values can be generally independent of cardiac output.

[0136] In an example, the system 100 (as depicted in FIG. 1A) can include acomputer readable medium including instructions that, when executed by a processor (e.g., the processing circuitry 104) cause the processor to perform a process for derivation of individual BSA and age-specific cardiac output fromultrasound measured single carotid blood flow. The process can involve analgorithm that performs calculations according to Equations 33-37, or any of the above Equations 1-32.

[0137] At 702, the process 700 can include calculated an expected cardiacoutput (CO) and an expected carotid blood flow percentage 702. Such acalculation can be based on a BSA for the particular patient (e.g., calculated via Equation 33, Equation 34, or Equation 35) and a normalized, age-specific BSA-based expected cardiac output (e.g., using cardiac index calculated viaEquation 36 and Equation 37). In an example, by multiplying normalizedexpected cardiac output by an expected single carotid blood flow percentage,a normalized carotid flow can be determined.Docket No. 6582.001WO1

[0138] At 704, the process 700 can include measuring, via a pulsed-wave ultrasound transducer array, actual single carotid flow at or near a patient carotid artery.

[0139] At 706, the process 700 can include determining a translated cardiac output from an actual single carotid flow. For example, the translated cardiac output can be determined using a model for translation of single carotid blood flow to cardiac output. Such an operation can involve, e.g., multiplying normalized expected cardiac output by a cardiac output factor to determine the translated cardiac output from carotid flow.

[0140] At 708, the process 700 can include calibrating an impedance cardiography (ICG) signal (e.g., the ICG signal 124 of FIG. 1B) based on the translated cardiac output.

[0141] FIG. 8 is a flowchart describing a process for patient monitoring to assess cardiophysiological function of a human patient. For example, the process 800 can be performed using the system 100 of FIG. 1A.

[0142] At 802, an ultrasound waveform from can be received a pulsed-wave ultrasound transducer array that is fixed at an external target body location of the patient and oriented toward a patient vessel. The ultrasound waveform can be obtained over a first time period. In an example, the process can involve receiving a corresponding (e.g., time-correlated) bioimpedance cardiac waveform data corresponding to the patient vessel during a second time period that encompasses the first period.

[0143] At 804, a plurality of waveform fiducials can be identified from the received ultrasound waveform, where an individual ultrasound waveform fiducial provides specific information about patient blood flow characteristics.

[0144] At 806, based on the identified waveform fiducials, the process can involve determining an ultrasound diagnostic indication of at least left ventricular ejection time (LVET) of the patient (step 230). This determination can include, e.g., sensing wall motion at the suprasternal aortic notch of the patient aorta using the pulsed-wave ultrasound transducer array. The process can also include measuring a diameter and cross-sectional area of the suprasternal aortic notch, e.g., via A-mode or B-mode scanning from an imager.Docket No. 6582.001WO1

[0145] At 808, the process can involve providing an indication of cardiophysiological function of the patient, such as based on a bioimpedance cardiac waveform and the ultrasound diagnostic indication as an input. For example, the plurality of identified fiducials can be used to validate or adjust the bioimpedance waveform fiducials, such as based on time-corresponding relationships.

[0146] In an example, process can involve controlling ultrasonic sensing via selective energization of individual elements within the transducer array. This can include establishing or adjusting energy levels at various elements to move the target region location between different positions, while sensing vessel size through detection of blood flow regions. The process can also include receiving additional ultrasound waveform data, e.g., from a continuous wave ultrasound transducer during the first period. Here, the continuous wave ultrasound transducer can provide sensing of higher maximum blood velocities compared to the pulsed-wave array alone. In an example, the process includes providing physical stimuli to the patient, such as a passive leg raise. In response to the physical stimuli, the process can involve comparison of ultrasound-derived blood flow indicators with time- correlate bioimpedance measurements. Based on this comparison, at least one of the ultrasound waveform or the bioimpedance cardiac waveform can be established or adjusted.

[0147] FIG. 9 illustrates generally an example of a block diagram of a machine 901 upon which any one or more of the techniques (e.g., methodologies) discussed herein may perform in accordance with some examples. In alternative embodiments, the machine 901 may operate as a standalone device or may be connected (e.g., networked) to other machines. In a networked deployment, the machine 901 may operate in the capacity of a server machine, a client machine, or both in server-client network environments. In an example, the machine 901 may act as a peer machine in peer-to-peer (P2P) (or other distributed) network environment. The machine 901 may be a personal computer (PC), a tablet PC, a set-top box (STB), a personal digital assistant (PDA), a mobile telephone, a web appliance, a network router, switch or bridge, or any machine capable of executing instructions (sequential or otherwise) that specify actions to be taken by thatDocket No. 6582.001WO1 machine. Further, while only a single machine is illustrated, the term “machine” shall also be taken to include any collection of machines that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methodologies discussed herein, such as cloud computing, software as a service (SaaS), other computer cluster configurations.

[0148] Examples, as described herein, may include, or may operate on, logic or a number of components, modules, or mechanisms. Modules are tangible entities (e.g., hardware) capable of performing specified operations when operating. A module includes hardware. In an example, the hardware may be specifically configured to carry out a specific operation (e.g., hardwired). In an example, the hardware may include configurable execution units (e.g., transistors, circuits, etc.) and a computer readable medium containing instructions, where the instructions configure the execution units to carry out a specific operation when in operation. The configuring may occur under the direction of the executions units or a loading mechanism. Accordingly, the execution units are communicatively coupled to the computer readable medium when the device is operating. In this example, the execution units may be a member of more than one module. For example, under operation, the execution units may be configured by a first set of instructions to implement a first module at one point in time and reconfigured by a second set of instructions to implement a second module.

[0149] Machine (e.g., computer system) 901 may include a hardware processor 902 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), a hardware processor core, or any combination thereof), a main memory 903 and a static memory 904, some or all of which may communicate with each other via an interlink (e.g., bus) 905. The machine 901 may further include a display unit 906, an alphanumeric input device 907 (e.g., a keyboard), and a user interface (UI) navigation device 908 (e.g., a mouse). In an example, the display unit 906, alphanumeric input device 907 and UI navigation device 908 may be a touch screen display. The machine 901 may additionally include a storage device (e.g., drive unit) 909, a signal generation device 910 (e.g., a speaker), a network interface device 911, and one or more sensors 912, such as a global positioning system (GPS) sensor, compass,Docket No. 6582.001WO1 accelerometer, or another sensor. The machine 901 may include an output controller 916, such as a serial (e.g., universal serial bus (USB), parallel, or other wired or wireless (e.g., infrared (IR), near field communication (NFC), etc.) connection to communicate or control one or more peripheral devices (e.g., a printer, card reader, etc.).

[0150] The storage device 909 may include a machine readable medium 913 that is non-transitory on which is stored one or more sets of data structures or instructions 914 (e.g., software) embodying or utilized by any one or more of the techniques or functions described herein. The instructions 914 may also reside, completely or at least partially, within the main memory 903, within static memory 904, or within the hardware processor 902 during execution thereof by the machine 901. In an example, one or any combination of the hardware processor 902, the main memory 903, the static memory 904, or the storage device 909 may constitute machine readable media.

[0151] While the machine readable medium 913 is illustrated as a single medium, the term “machine readable medium” may include a single medium or multiple media (e.g., a centralized or distributed database, or associated caches and servers) configured to store the one or more instructions 914.

[0152] The term “machine readable medium” may include any medium that is capable of storing, encoding, or carrying instructions for execution by the machine 901 and that cause the machine 901 to perform any one or more of the techniques of the present disclosure, or that is capable of storing, encoding or carrying data structures used by or associated with such instructions. Non- limiting machine-readable medium examples may include solid-state memories, and optical and magnetic media. Specific examples of machine- readable media may include: non-volatile memory, such as semiconductor memory devices (e.g., Electrically Programmable Read-Only Memory (EPROM), Electrically Erasable Programmable Read-Only Memory (EEPROM)) and flash memory devices; magnetic disks, such as internal hard disks and removable disks; magneto-optical disks; and CD-ROM and DVD- ROM disks.

[0153] The instructions 914 may further be transmitted or received over a communications network 915 using a transmission medium via the networkDocket No. 6582.001WO1 interface device 911 utilizing any one of a number of transfer protocols (e.g., frame relay, internet protocol (IP), transmission control protocol (TCP), user datagram protocol (UDP), hypertext transfer protocol (HTTP), etc.). Example communication networks may include a local area network (LAN), a wide area network (WAN), a packet data network (e.g., the Internet), mobile telephone networks (e.g., cellular networks), Plain Old Telephone (POTS) networks, and wireless data networks (e.g., Institute of Electrical and Electronics Engineers (IEEE) 802.11 family of standards known as Wi-Fi®, IEEE 802.16 family of standards known as WiMax®), IEEE 802.15.4 family of standards, peer-to- peer (P2P) networks, among others. In an example, the network interface device 911 may include one or more physical jacks (e.g., Ethernet, coaxial, or phone jacks) or one or more antennas to connect to the communications network 915. In an example, the network interface device 911 may include a plurality of antennas to wirelessly communicate using at least one of single- input multiple-output (SIMO), multiple-input multiple-output (MIMO), or multiple-input single-output (MISO) techniques. The term “transmission medium” shall be taken to include any intangible medium that is capable of storing, encoding or carrying instructions for execution by the machine 901, and includes digital or analog communications signals or other intangible medium to facilitate communication of such software.

[0154] The above Detailed Description can include references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention can be practiced. These embodiments are also referred to herein as “examples.” Such examples can include elements in addition to those shown or described. However, the present inventors also contemplate examples in which only those elements shown or described are provided. Moreover, the present inventors also contemplate examples using any combination or permutation of those elements shown or described (or one or more aspects thereof), either with respect to a particular example (or one or more aspects thereof), or with respect to other examples (or one or more aspects thereof) shown or described herein.

[0155] In the event of inconsistent usages between this document and any documents so incorporated by reference, the usage in this document controls.Docket No. 6582.001WO1 In this document, the terms “including” and “in which” are used as the plain- English equivalents of the respective terms “comprising” and “wherein.” Also, in the following claims, the terms “including” and “comprising” are open-ended, that is, a system, device, article, composition, formulation, or process that can include elements in addition to those listed after such a term in a claim are still deemed to fall within the scope of that claim.

[0156] In this document, the terms “a” or “an” are used, as is common in patent documents, to include one or more than one, independent of any other instances or usages of “at least one” or “one or more.” In this document, the term “or” is used to refer to a nonexclusive or, such that “A or B” can include “A but not B,” “B but not A,” and “A and B,” unless otherwise indicated. In this document, the terms “including” and “in which” are used as the plain- English equivalents of the respective terms “comprising” and “wherein.” Also, in the following claims, the terms “including” and “comprising” are open-ended, that is, a system, device, article, composition, formulation, or process that can include elements in addition to those listed after such a term in a claim are still deemed to fall within the scope of that claim. Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are used merely as labels, and are not intended to impose numerical requirements on their objects.

[0157] The above description is intended to be illustrative, and not restrictive. For example, the above-described examples (or one or more aspects thereof) can be used in combination with each other. Other embodiments can be used, such as by one of ordinary skill in the art upon reviewing the above description. The Abstract is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. Also, in the above Detailed Description, various features can be grouped together to streamline the disclosure. This should not be interpreted as intending that an unclaimed disclosed feature is essential to any claim. Rather, inventive subject matter can lie in less than all features of a particular disclosed embodiment. Thus, the following claims are hereby incorporated into the Detailed Description as examples or embodiments, with each claim standing on its own as a separate embodiment, and it isDocket No. 6582.001WO1 contemplated that such embodiments can be combined with each other in various combinations or permutations. The scope of the invention should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

Docket No. 6582.001WO1 CLAIMS What is claimed is:

1. A method for patient monitoring to assess cardiophysiological function of a human patient, the method comprising: receiving, from a pulsed-wave ultrasound transducer array, fixed at an external target body location of the patient toward a patient vessel, an ultrasound waveform obtained over a first period; identifying a plurality of waveform fiducials of the ultrasound waveform, an individual ultrasound waveform fiducial providing an indication of patient blood flow; determining, based on the plurality of waveform fiducials, an ultrasound diagnostic indication of at least left ventricular contraction time (LVET) of the patient; and providing an indication of the cardiophysiological function of the patient, based on a bioimpedance cardiac waveform and the ultrasound diagnostic indication as an input.

2. The method of claim 1, comprising: receiving the bioimpedance cardiac waveform corresponding with the patient vessel during a second period, the second period larger than and encompassing the first period; and at least one of validating or adjusting at least one bioimpedance waveform fiducial of the bioimpedance cardiac waveform based on a time- corresponding individual ultrasound waveform fiducial.

3. The method of claim 1, comprising: sensing, via the pulsed-wave ultrasound transducer array, wall motion at a suprasternal aortic notch of a patient aorta; determining, from imaging, a diameter of the suprasternal aortic notch of the patient aorta; and processing the ultrasound waveform to determine a cardiac cycle characteristic of a cardiac cycle waveform, based on a calculation of aortic area and independent of bioimpedance cardiography;Docket No. 6582.001WO1 wherein the determined cardiac cycle characteristic is based on the sensed wall motion and measured diameter of the aorta.

4. The method of claim 1, comprising selectively energizing an individual element of a plurality of elements included in the transducer array to control a target region location at which the ultrasound waveform is sensing.

5. The method of claim 4, comprising: establishing or adjusting an energy at one or more of the plurality of elements to move the target region location between a first target region location and a second target region location; and sensing, via pulses of the ultrasound waveform, a size of a region exhibiting blood flow and indicative of a vessel size.

6. The method of claim 4, comprising orienting individual elements of the plurality of elements in different directions with respect to one another and toward a patient carotid artery.

7. The method of claim 1, wherein the pulsed-wave ultrasound transducer array includes at least one of a non-imaging Doppler or a non-imaging ultrasound.

8. The method of claim 1, comprising displaying the indication of cardiac output, via a user interface, to aid in diagnostic assessment of the human patient.

9. The method of claim 1, comprising receiving, from a continuous wave ultrasound transducer, an additional ultrasound waveform obtained over the first period, wherein the continuous wave ultrasound transducer is capable of sensing a greater blood velocity than the pulsed-wave ultrasound transducer array.

10. The method of claim 1, wherein the pulsed-wave ultrasound transducer array includes a concentric circular array surrounding a rectangular matrix.Docket No. 6582.001WO1 11. The method of claim 1, comprising inform an auxiliary measurement of patient blood flow based on the identified plurality of waveform fiducials of the ultrasound waveform.

12. The method of claim 1, comprising: providing a physical stimulus to the human patient; comparing the indication of patient blood flow identified from the ultrasound waveform with a bioimpedance measurement of flow following the physical stimulus; and calibrating at least one of the ultrasound waveform or the bioimpedance cardiac waveform based on the comparison.

13. The method of claim 12, wherein the physical stimulus is a passive leg raise.

14. A system for patient monitoring to assess cardiophysiological function of a human patient, the system comprising: a pulsed-wave ultrasound transducer array, configured to be fixed at a first external target body location of the patient toward a patient vessel and to provide an ultrasound waveform obtained over a first period; processing circuitry configured to: identify a plurality of waveform fiducials of the ultrasound waveform, an individual ultrasound waveform fiducial providing an indication of patient blood flow; determine, based on the plurality of waveform fiducials, an ultrasound diagnostic indication of at least left ventricular contraction time (LVET) of the patient; and provide an indication of the cardiophysiological function of the patient, based on a bioimpedance cardiac waveform and the ultrasound diagnostic indication as an input.

15. The system of claim 14, comprising: at least two bioimpedance transducers, configured to be fixed at a second external target body location of the patient and to provide theDocket No. 6582.001WO1 bioimpedance cardiac waveform corresponding with the patient vessel during a second period, wherein the second period is larger than and encompasses the first period; wherein the processing circuitry is configured to validate or adjust at least one bioimpedance waveform fiducial of the bioimpedance cardiac waveform based on a time-corresponding individual ultrasound waveform fiducial.

16. The system of claim 14, comprising an imager configured to provide imaging data of internal patient anatomy when applied at or near the first external target body location, wherein the processing circuitry is configured to: sense, via the pulsed-wave ultrasound transducer array, wall motion at a suprasternal aortic notch of a patient aorta; determine, based on the imaging data received from the imager, a diameter of the suprasternal aortic notch of the patient aorta; and process the ultrasound waveform to determine a cardiac cycle characteristic of a cardiac cycle waveform, based on a calculation of aortic area and independent of bioimpedance cardiography, wherein the determined cardiac cycle characteristic is based on the sensed wall motion and measured diameter of the aorta.

17. The system of claim 14, wherein the transducer array includes a plurality of elements, wherein the transducer array is configured to selectively energize an individual element of the transducer array to control a target region location at which the ultrasound waveform is sensing.

18. The system of claim 17, wherein the processing circuitry is configured to: establish or adjust an energy at one or more of the plurality of elements to move the target region location between a first target region location and a second target region location; and sense, via pulses of the ultrasound waveform, a size of a region exhibiting blood flow and indicative of a vessel size.Docket No. 6582.001WO1 19. The system of claim 17, wherein the transducer array includes individual elements of the plurality of elements oriented in different directions with respect to one another and toward a patient carotid artery.

20. The system of claim 14, wherein the pulsed-wave ultrasound transducer array includes at least one of a non-imaging Doppler or a non-imaging ultrasound.

21. The system of claim 14, comprising a user interface configured to display the indication of cardiac output, for aiding in diagnostic assessment of the human patient.

22. The system of claim 14, comprising a continuous wave ultrasound transducer configured to provide an additional ultrasound waveform obtained over the first period, wherein the continuous wave ultrasound transducer is capable of sensing a greater maximum blood velocity than that of the pulsed-wave ultrasound transducer array.

23. The system of claim 14, wherein the pulsed-wave ultrasound transducer array includes a concentric circular array surrounding a rectangular matrix.

24. The system of claim 14, wherein the processing circuitry is configured to, in response to an indication of a physical stimulus applied to the human patient; compare the indication of patient blood flow identified from the ultrasound waveform with a bioimpedance measurement of flow following the physical stimulus; and calibrate at least one of the ultrasound waveform or the bioimpedance cardiac waveform based on the comparison.

25. The system of claim 24, wherein the physical stimulus is a passive leg raise.

26. A non-transitory computer-readable storage medium, the computer- readable storage medium including instructions that when executed by a processor, cause the processor to:Docket No. 6582.001WO1 receive, from a pulsed-wave ultrasound transducer array, fixed at an external target body location of the patient toward a patient vessel, an ultrasound waveform obtained over a first period; identify a plurality of waveform fiducials of the ultrasound waveform, an individual ultrasound waveform fiducial providing an indication of patient blood flow; determine, based on the plurality of waveform fiducials, an ultrasound diagnostic indication of at least left ventricular contraction time (LVET) of the patient; and provide an indication of the cardiophysiological function of the patient, based on a bioimpedance cardiac waveform and the ultrasound diagnostic indication as an input.

27. The computer-readable storage medium of claim 26, comprising instructions that when executed by the processor, cause the processor to: receive the bioimpedance cardiac waveform corresponding with the patient vessel during a second period, the second period larger than and encompassing the first period; and at least one of validate or adjust at least one bioimpedance waveform fiducial of the bioimpedance cardiac waveform based on a time- corresponding individual ultrasound waveform fiducial.

28. The computer-readable storage medium of claim 26, comprising instructions that when executed by the processor, cause the processor to: sense, via the pulsed-wave ultrasound transducer array, wall motion at a suprasternal aortic notch of a patient aorta; determine, from imaging, a diameter of the suprasternal aortic notch of the patient aorta; and process the ultrasound waveform to determine a cardiac cycle characteristic of a cardiac cycle waveform, based on a calculation of aortic area and independent of bioimpedance cardiography; wherein the determined cardiac cycle characteristic is based on the sensed wall motion and measured diameter of the aorta.Docket No. 6582.001WO1 29. The computer-readable storage medium of claim 26, comprising instructions that when executed by the processor, cause the processor to selectively energize an individual element of a plurality of elements included in the transducer array to control a target region location at which the ultrasound waveform is sensing.

30. The computer-readable storage medium of claim 29, comprising instructions that when executed by the processor, cause the processor to: establish or adjust an energy at one or more of the plurality of elements to move the target region location between a first target region location and a second target region location; and sense, via pulses of the ultrasound waveform, a size of a region exhibiting blood flow and indicative of a vessel size.

31. The computer-readable storage medium of claim 29, comprising instructions that when executed by the processor, cause the processor to orient individual elements of the plurality of elements in different directions with respect to one another and toward a patient carotid artery.

32. The computer-readable storage medium of claim 26, wherein the pulsed- wave ultrasound transducer array includes at least one of a non-imaging Doppler or a non-imaging ultrasound.

33. The computer-readable storage medium of claim 26, comprising instructions that when executed by the processor, cause the processor to display the indication of cardiac output, via a user interface, to aid in diagnostic assessment of the human patient.

34. The computer-readable storage medium of claim 26, comprising instructions that when executed by the processor, cause the processor to receive, from a continuous wave ultrasound transducer, an additional ultrasound waveform obtained over the first period, wherein the continuous wave ultrasound transducer is capable of sensing a greater maximum blood velocity than that of the pulsed-wave ultrasound transducer array.Docket No. 6582.001WO1 35. The computer-readable storage medium of claim 26, wherein the pulsed- wave ultrasound transducer array includes a concentric circular array surround a rectangular matrix.

36. The computer-readable storage medium of claim 26, comprising instructions that when executed by the processor, cause the processor to augment an auxiliary measurement of patient blood flow based on the identified plurality of waveform fiducials of the ultrasound waveform.

37. The computer-readable storage medium of claim 26, comprising instructions that when executed by the processor, cause the processor to: provide a physical stimulus to the human patient; compare the indication of patient blood flow identified from the ultrasound waveform with a bioimpedance measurement of flow following the physical stimulus; and calibrate at least one of the ultrasound waveform or the bioimpedance cardiac waveform based on the comparison.

38. The computer-readable storage medium of claim 37, wherein the physical stimulus is a passive leg raise.

Images