WO2022070206A1

WO2022070206A1 - Augmented multimodal flow mediated dilatation

Info

Publication number: WO2022070206A1
Application number: PCT/IN2021/050880
Authority: WO
Inventors: Jayaraj JOSEPH; Dinu Santha Chandran; Nabeel Pilaparambil Mashood; Raj Kiran Vangapandu; Mohanasankar SIVAPRAKASAM
Original assignee: Healthcare Technology Innovation Centre; Indian Institute Of Technology Madras
Priority date: 2020-09-30
Filing date: 2021-09-09
Publication date: 2022-04-07

Abstract

An image-free augmented multimodal system is used for the assessment of endothelial function and local stiffness parameters of a target artery. The system comprises a flow restrictor, multimodal probe, and measurement module. The flow restrictor controls blood flow through the artery. A probe with an ultrasound transducer and a pressure sensor is positioned near the artery. The ultrasound transducer generates ultrasound echo signals based on the vascular dimensions and the pressure sensor generates pressure signals based on the arterial pressure. A microcontroller receives the simultaneously captured ultrasound echo signals and pressure signals. The microcontroller generates ultrasound frames based on the ultrasound echo signals and a pressure pulse wave based on the pressure signal. The endothelial function and local stiffness parameters are determined by the measurement module based on augmented multimodal flow mediated dilatation (AM-FMD) technique using the ultrasound frames and the pressure pulse wave.

Description

AUGMENTED MULTIMODAL FLOW MEDIATED DILATATION

FIELD OF THE INVENTION

The present invention is related to a device that is used for endothelial function assessment from an artery using augmented multimodal flow mediated dilatation (AM-FMD).

BACKGROUND OF THE INVENTION

Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

In the current art, preventive strategies are becoming the key focus of attention in the fight against cardiovascular diseases. One such effective preventive strategy is to identify those individuals who are at a higher risk of developing future cardiovascular events and concentrate preventive measures at the earliest through counselling and medicines, as deemed appropriate. Unfortunately, the predictive performance of conventional risk factors is suboptimal in the early stages of the disease. Structural alterations of arterial vessels are a common pathway in the early stages of cardiovascular diseases, which initiate and promote atherogenic changes in the conduit arteries by hampering the functions of the endothelial layer (the inner lining of an artery) and stiffening the major central elastic arteries. Non-invasive assessment of endothelial dysfunction has an established pathophysiologic role in the initiation and progression of atherosclerotic cardiovascular disease. It could improve patient risk stratification and the implementation of effective preventive strategies.

The most widely accepted method for non-invasive assessment of arterial endothelial function is an ultrasonographic measurement of brachial artery Flow Mediated Dilatation (FMD). It involves ultrasound image-based measurement of changes in the brachial artery diameter, which has been subjected to circulatory arrest for a short period by application of an occluding cuff. The method involves significant post-processing steps to analyse the images, identify the artery, and reliably capture dynamic changes in arterial diameter. As such, the imaging-based FMD requires an expensive (and bulky) ultrasound system with high spatial-resolution or tracking -resolution, trained operators, and is cumbersome to get reliable results. Furthermore, due to the lack of automated real-time FMD systems, sometimes the whole examination may have to be rejected due to poor or unstable image sequences resulting in non-reliable diameter estimates. Subsequently, the routine clinical use of brachial FMD is hampered by the unavailability of easy-to-use technology for reliable assessment, at an affordable cost.

More importantly, there is a critical lapse in the current FMD methods, which is: ignoring the change in arterial pressure associated with the phase of reactive hyperemia when changes in arterial diameters are captured to assess the endothelium-dependent relaxation of arterial smooth muscle. Since arterial diameters are directly influenced by transmural pressure, as determined by the fundamental pressure-diameter relations, lack of information on local pressure fluctuations could make the FMD estimates unreliable and can add to its variability across subjects and time points of assessment. The existing method of assessment of FMD based on ultrasonographic imaging does not allow simultaneous assessment of vascular diameter changes and pressure at the same arterial location. Therefore, there is a need for a device that performs a simultaneous assessment of vascular diameter changes and pressure at the same arterial location. More particularly, a device that performs simultaneous measurement of local arterial pressure along with dimensional changes to better quantify the endothelial dysfunction from target arterial sites.

SUMMARY OF THE INVENTION

It is intended that all such features, and advantages be included within this description, be within the scope of the present invention, and be protected by the accompanying claims. The following summary is provided to facilitate an understanding of some of the innovative features unique to the disclosed embodiment and is not intended to be a full description. A full appreciation of the various aspects of the embodiments disclosed herein can be gained by taking the entire specification, claims, drawings, and abstract as a whole.

The present invention discloses a device that addresses the need for a method or system that performs simultaneous measurement of local arterial pressure along with arterial dimensional changes to assess endothelial function and better quantify the endothelial dysfunction from target arterial sites. The invention disclosed herein is a compact, easy-to-use, field-deployable ultrasound-based device, that does not rely on ultrasound image construction and performs; (a) Simultaneous and continuous measurement of arterial pressure and vascular dimensions (both as value and waveform), and their dynamic variations in real-time, from target arteries, (b) Comprehensive assessment of the endothelial function and quantification of endothelial response and dysfunction by augmented multimodal flow mediated dilatation (AM-FMD) technique employing simultaneous measurement of arterial dimensions and transmural arterial pressure at the same arterial site or from a segment of a target artery, and (c) Assessment of the endothelial function by conventional flow mediated dilatation (FMD) technique at target arteries such as, but not limited to, brachial, radial, femoral, tibial etc., without the use of ultrasonographic imaging systems.

The image-free augmented multimodal system that is disclosed here is used for simultaneous, continuous, and real-time non-invasive assessment of vascular dimensions, arterial pressure, endothelial function, and local stiffness indices of a target artery. The image-free augmented multimodal system comprises an integrated flow restrictor, an ultrasound transducer, a high voltage pulser-receiver, an arterial pressure wave detector, and a measurement module. The integrated flow restrictor controls blood flow through the target artery and the ultrasound transducer and a pressure sensor form parts of one or more probes. Each probe is positioned in contact with the skin-tissue above the target artery, and the ultrasound transducer generates ultrasound echo signals based on the vascular dimensions, and the pressure sensor generates pressure signals based on the arterial transmural pressure.

The high voltage pulser-receiver is in communication with the ultrasound transducer to send the ultrasound echo signals towards the target artery and to transmit the received ultrasound echo signals to a microcontroller. The arterial pressure wave detector is in communication with the pressure sensor to receive the pressure signals and converts the generated pressure signal into a pressure pulse wave that is communicated to the microcontroller. The microcontroller generates a set of ultrasound frames based on the ultrasound echo signals and a pressure pulse wave based on the pressure sensor signal. The measurement module is controlled by at least one processor and is in communication with the ultrasound transducer and the pressure sensor to receive the ultrasound frames and the pressure pulse wave respectively. The vascular dimensions, arterial pressure, endothelial function, and local stiffness indices of the target artery are determined by the measurement module based on the ultrasound frames and the pressure pulse wave. In an embodiment, the high voltage pulser-receiver comprises a transceiver, a transmitterreceiver switch, and a high voltage generation module. The transmitter-receiver switch connects the ultrasound transducer to the transceiver. The high voltage generation module works in combination with the transceiver to generate high-voltage excitation pulses and receives a signal from the ultrasound transducer that is associated with dynamic motion of the target artery and arterial dimension of that target artery. The microcontroller is in communication with the transceiver and the transmitter-receiver switch. In an embodiment, the measurement module comprises an automatic artery wall recognition module, and the microcontroller communicates the ultrasound frames that are based on the information detected by the ultrasound transducer to the automatic artery wall recognition module that recognises the locations of the artery walls.

In an embodiment, the measurement module comprises an automatic wall tracking module, where the automatic wall recognition module communicates the information of the recognised wall locations to the automatic wall tracking module that tracks the profile of the motion and vibration of artery walls. In an embodiment, the measurement module comprises a diameterdistension evaluation module, and wherein the tracked profile of the artery walls is communicated to the diameter-distension evaluation module that generates a diameter and distension waveform based on the dynamics of arterial wall motion and vibration.

In an embodiment, the measurement module comprises an arterial pressure wave module, and the microcontroller communicates the digitized pressure pulse wave to the arterial pressure wave module that derives a digital domain waveform from of the pressure pulse wave data communicated by the microcontroller. In an embodiment, the measurement module comprises a processing module, where the derived digital domain waveform of the digitized pressure pulse wave is communicated to the processing module that processes the derived waveform. In an embodiment, the measurement module comprises a pressure-value-and-waveform extraction module, and where the processing module communicates the processed waveform to the pressure-value-and-waveform extraction module that extracts a set of pressure waveforms and corresponding arterial pressure values.

In an embodiment, the measurement module comprises a cycle-cutting module, where waveform data from the diameter-distension evaluation module and the pressure-value-and- waveform extraction module are communicated to the cycle-cutting module that performs synchronized automatic cycle cutting and selection of the waveform data for individual heartbeat over continuous cardiac cycles. The waveform data includes the diameter with the distension waveform and the set of pressure waveforms with the corresponding arterial pressure values. In an embodiment, the measurement module comprises a cycle-analysis module that receives the processed waveform data for the individual heartbeats over the continuous cardiac cycles from the cycle-cutting module and analyses the processed waveform data to generate time-varying beat-by-beat end-diastolic diameter, distension, pressure, and other fiducial values.

In an embodiment, the measurement module comprises a cycle- segregation module, where the cycle-analysis module transmits the generated time-varying beat-by-beat end-diastolic diameter, distension, pressure, and fiducial values to the cycle-segregation module. The cyclesegregation module segregates the beat-to-beat values for the baseline and intervened physical- physiological states, constituting baseline state, low flow state, and vasodilation state. In an embodiment, the measurement module comprises a range-analysis module that receives the segregated values for the physical-physiological states, constituting baseline state, low flow state, and vasodilation state. The range-analysis module generates baseline, minimum, peak, and recovery values of end-diastolic diameter and the corresponding distension and pressure based on the segregated beat-to-beat diameter, distension, and pressure values.

In an embodiment, the measurement module comprises an endothelial function-evaluation module, where the range-analysis module communicates the generated baseline, minimum peak, and recovery values of end-diastolic diameter and the corresponding distension, pressure, and fiducial measures to the endothelial function-evaluation module. The endothelial functionevaluation module evaluates and assesses the measures and indices of the endothelial functions and quantify endothelial dysfunction of the target artery.

In an embodiment, the endothelial function-evaluation module generates augmented multimodal measurements of endothelial function, vascular structure, and vascular function over continuous cardiac cycles. The values of individual cardiac cycles and their average comprise absolute value, peak change, relative change, rate of change, and gradient in structural dimensions of the target artery in response to excitation produced by intervention and reactivity. The values of the individual cardiac cycles and their average also comprise absolute value, peak change, relative change, rate of change, and gradient in transmural pressure, luminal pressure, and mechanical stress of the target artery in response to excitation produced by the intervention and the reactivity. The values of the individual cardiac cycles and their average also comprise absolute value, peak change, relative change, rate of change, and gradient in material properties of the target artery in response to excitation produced by the intervention and the reactivity.

Finally, the values of the individual cardiac cycles and their average also comprise absolute value, peak change, relative change, rate of change, and gradient in static and dynamic responses of the target artery to excitation produced by the intervention and the reactivity. In an embodiment, the measurement module comprises a local stiffness evaluation module, where data comprising the generated time-varying beat-by-beat end-diastolic diameter, distension, pressure, and fiducial values from the cycle-analysis module are communicated to the local stiffness-evaluation module. The local stiffness-evaluation module evaluates and assesses the local stiffness indices of the target artery based on the received data.

BRIEF DESCRIPTION OF DRAWINGS

The invention can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present invention. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views.

Figure 1 exemplarily illustrates an image-free augmented multimodal system that is used for endothelial function assessment from target arterial sites using augmented multimodal flow mediated dilatation (AM-FMD) technique.

Figure 2 exemplarily illustrates a schematic view of a hardware architecture of the image-free augmented multimodal system and software architecture that is associated with the hardware architecture, wherein the schematic view illustrates different steps involved in performing a simultaneous assessment of arterial dimensions and local pressure for reliable evaluation of endothelial function. Figure 3 exemplarily illustrates a flow diagram that illustrates a method for simultaneous, continuous and real-time non-invasive assessment of vascular dimensions, arterial pressure, endothelial function, and local stiffness indices of a target artery.

DESCRIPTION OF THE INVENTION

The aim of the present invention is to provide a device that performs simultaneous measurement of local arterial pressure along with dimensional changes to better quantify the endothelial dysfunction from target arterial sites. The above aim has been achieved using the aforementioned device that performs endothelial function assessment from target arterial sites using augmented multimodal flow mediated dilatation (AM-FMD) technique.

The foregoing advantages as well as the particular construction of the device that performs endothelial function assessment will become more noticeable and understandable from the following detail description thereof when read in conjunction with the accompanying drawings.

The present invention is an image-free augmented multimodal system equipped with an integrated flow restrictor and a multimodal probe that employs ultrasound and pressure (or force) transducers, along with intelligent algorithms, to perform AM-FMD with simultaneous assessment of arterial dimensions and local arterial pressure for reliable evaluation of endothelial function and quantification of endothelial dysfunction and local arterial stiffening.

Figure 1 exemplarily illustrates an image-free augmented multimodal system 100 that is used for endothelial function assessment from target arterial sites using augmented multimodal flow mediated dilatation (AM-FMD) technique. The image-free augmented multimodal system 100 employs a compact probe 102 (with ultrasound and pressure transducers) that is used to capture the arterial dimensions and pressure simultaneously, for AM-FMD. Furthermore, Figure 1 shows the use of an integrated flow restrictor 104 to induce circulatory arrest for a short period. The image-free augmented multimodal system 100 is also used for non-invasive assessment of endothelial function and real-time quantification of endothelial dysfunction and local arterial stiffening with provisions for image-free, minimal operator dependency, portability, and field deploy ability. In an embodiment, the image-free augmented multimodal system 100 is connected to any processor enabled device 106, for example, laptop computer/tablet/mobile phone, or the image-free augmented multimodal system 100 is configured to be operated independently.

As previously described, the image-free augmented multimodal system 100 comprises an integrated flow restrictor 104, which occludes the target artery 108 in a controlled manner as per the conventional FMD or AM-FMD measurement protocols. The image-free augmented multimodal system 100 is equipped with an integrated multimodal probe 102 that employs an ultrasound transducer 110 and a pressure sensor (or force sensor) 112 for the simultaneous measurement of vascular dimensions and arterial pressure, respectively. Therefore, the image- free augmented multimodal system 100 has a compact probe 102 with multimodal design wherein the compact probe 102 comprises ultrasound and pressure transducers/sensors 110 and 112, respectively. In another embodiment, the ultrasound transducer 110 and a pressure sensor 112 are positioned in different probes 102. The image-free augmented multimodal system 100 performs simultaneous measurement of the arterial pressure and diameter from a single arterial site or from an arterial segment, with accurate measurements across the target arteries 108 such as carotid, brachial, radial, femoral, tibial, etc. The measurement is determined, by the processor enabled device/hardware 106, when the multimodal probe 102 transmits ultrasound and pressure data regarding vascular dimensions and arterial pressure, respectively, to the processor enabled device/hardware 106, such as the custom electronics with tablet computer(s) 106 shown in figure 1. The arterial pressure and vascular dimensions (both as value and waveform), and their dynamic variations in real-time, are obtained from target arteries 108. The processor enabled device/hardware 106 digitizes the ultrasound and pressure data and transmits the digitized ultrasound and pressure data, as shown in Figure 1, to the AM-FMD or FMD software 114 that generates graphical models that include, for example, Ultrasound Echo Amplitude Vs Time, Arterial Diameter Vs Time, and Arterial Pressure Vs Time. The AM- FMD or FMD results are then displayed on a result and display panel 116.

The image-free augmented multimodal system 100 performs a real-time automated evaluation of arterial dimensions without an image using intelligent algorithms for real-time tracking of the arterial wall without any input from the operator, and hence surpass the accuracy obtainable by conventional imaging-based estimation of arterial diameters. A high temporal resolution offered by the device ensures precise tracking of dynamic variations in the vascular dimensions. The approach using the image-free augmented multimodal system 100 using AM- FMD with simultaneous measurement of arterial dimensions and pressure waveforms from the same artery location or an arterial segment gives more accurate and precise estimates of the endothelial function, qualification of the endothelial response and dysfunction along with other relevant parameters such as arterial dimensions and local vascular stiffness, thereby enhancing the utility of FMD as a predictive and risk stratifying tool. The image-free augmented multimodal system 100 also performs conventional FMD at any superficial arterial site without the need for an image while offering high resolution and precise measurement of dynamic variations in arterial diameter. The measurement sites for AM-FMD or conventional FMD include all the arterial sites where the artery can be occluded for sufficient time as per the protocol. For example, but not limited to the brachial, radial, femoral, and tibial arteries.

Referring to Figures 2 and 3, Figure 2 exemplarily illustrates a schematic view of a hardware architecture 202 of the image-free augmented multimodal system 100 and software architecture or measurement module 204 that is associated with the hardware architecture 202, wherein the schematic view illustrates different steps involved in performing a simultaneous assessment of arterial dimensions and local arterial pressure for reliable evaluation of endothelial function. Figure 3 exemplarily illustrates a flow diagram that illustrates a method for simultaneous, continuous and real-time non-invasive assessment of vascular dimensions, arterial pressure, endothelial function, and local stiffness indices of a target artery.

In further reference to Figures 2 and 3, the image-free augmented multimodal system 100 is powered by a power supply unit 210. The image-free augmented multimodal system 100 that is disclosed here is used for simultaneous, continuous and real-time non-invasive assessment of vascular dimensions, arterial pressure, endothelial function, and local stiffness indices of a target artery 108. The image-free augmented multimodal system 100 comprises an integrated flow restrictor 104, an ultrasound transducer 110, a pressure sensor 112, a high voltage pulserreceiver 214, an arterial pressure wave detector 206, and a measurement module 204. The integrated flow restrictor 104 controls 302 blood flow through the target artery 108 and the ultrasound transducer 110 and the pressure sensor 112 forms parts of one or more probes 102. The ultrasound transducer 110 that is positioned in one of the probes 102 generate ultrasound echo signals based on the vascular dimensions. Each probe 102 is positioned 304 in contact with the skin-tissue above the target artery 108 and the ultrasound transducer 110 sends 306 ultrasound echo signals towards the target artery and the pressure sensor 112 generates 308 pressure signals based on the arterial transmural pressure. The high voltage pulser-receiver 214 is in communication with the ultrasound transducer 110 to generate 310 the ultrasound echo signals based on the vascular dimensions of the target artery 108 and to transmit the received ultrasound echo signals to a microcontroller 208. The arterial pressure wave detector 206 is in communication with the pressure sensor 112 to receive the pressure signals and converts 312 the generated pressure signal into a pressure pulse wave that is communicated to the microcontroller 208. The microcontroller 208 generates 314 a set of ultrasound frames based on the ultrasound echo signals and a pressure pulse wave based on the pressure sensor signal. The measurement module 204 is controlled by at least one processor and is in communication with the microcontroller 208, ultrasound transducer, 110 and the pressure sensor 112 to receive the ultrasound frames and the pressure pulse wave respectively. The vascular dimensions, arterial pressure, endothelial function, and local stiffness indices of the target artery 108 are determined 316 by the measurement module 204 based on the ultrasound frames and the pressure pulse wave.

In an embodiment, the high voltage pulser-receiver 214 comprises a transceiver 216, a transmitter-receiver switch 212, and a high voltage generation module 218. The transmitterreceiver switch 212 connects the ultrasound transducer 110 to the transceiver 216. The high voltage generation module 218 works in combination with the transceiver 216 to generate high- voltage excitation pulses and receive an echo signal from the ultrasound transducer 110 that is associated with dynamic motion of the target artery 108 and the arterial dimension of that target artery 108. The microcontroller 208 is in communication with the transceiver 216 and the transmitter-receiver switch 212. The measurement module 204 comprises an automatic artery wall recognition module 220. The microcontroller 208 communicates the ultrasound frames that are based on the information detected by the ultrasound transducer 110 to the automatic artery wall recognition module 220 that recognises the locations of the artery walls.

In an embodiment, the measurement module 204 comprises an automatic wall tracking module 222. The automatic artery wall recognition module 220 communicates the information of the recognised wall locations to the automatic wall tracking module 222 that tracks the profile of the dynamic artery wall motion and vibrations. The measurement module 204 comprises a diameter-distension evaluation module 224. The tracked profile of the artery walls is communicated to the diameter-distension evaluation module 224 that generates a diameter and distension waveform based on the motion and vibration of the artery walls. The measurement module 204 comprises an arterial pressure wave module 226. The microcontroller 208 communicates the digitized pressure pulse wave to the arterial pressure wave module 226 that derives a digital domain waveform of the pressure pulse wave data communicated by the microcontroller 208.

In an embodiment, the measurement module 204 comprises a processing module 228, where the derived digital domain waveform of the digitized pressure pulse wave is communicated to the processing module 228 that processes the derived waveform. The measurement module 204 comprises a pressure-value-and-waveform extraction module 230. The processing module 228 communicates the processed waveform to the pressure-value-and-waveform extraction module 230 that extracts a set of arterial pressure waveforms and corresponding pressure values. The measurement module 204 comprises a cycle-cutting module 232. The waveform data from the diameter-distension evaluation module 224 and the pressure-value-and- waveform extraction module 230 are communicated to the cycle-cutting module 232 that performs synchronized automatic cycle cutting and selection of the waveform data for individual heartbeat over continuous cardiac cycles. The waveform data includes the diameter with the distension waveform and the set of pressure waveforms with the corresponding arterial pressure values.

In an embodiment, the measurement module 204 comprises a cycle-analysis module 234 that receives the processed waveform data for the individual heartbeats over the continuous cardiac cycles from the cycle-cutting module 232 and analyses the processed waveform data to generate time- varying beat-by-beat end-diastolic diameter, distension, pressure values, and related fiducial measures. The measurement module 204 comprises a cycle-segregation module 236. The cycle-analysis module 234 transmits the generated time-varying beat-by-beat end- diastolic diameter, distension, pressure, fiducial values to the cycle-segregation module 236. The cycle- segregation module 236 segregates the beat-to-beat values for the baseline and intervened physical-physiological states, constituting baseline state, low flow state, and vasodilation state.

In an embodiment, the measurement module 204 comprises a range-analysis module 238 that receives the segregated values for the physical-physiological states, constituting baseline state, low flow state, and vasodilation state. The range-analysis module 238 generates baseline, minimum, peak, and recovery values of end-diastolic diameter and the corresponding distension and pressure based on the segregated beat-to-beat diameter, distension, pressure, and fiducial values. The measurement module 204 comprises an endothelial functionevaluation module 242. The range-analysis module 238 communicates the generated baseline, minimum peak, and recovery values of end-diastolic diameter and the corresponding distension and pressure, along with related fiduciary measures, to the endothelial function-evaluation module 242. The endothelial function-evaluation module 242 evaluates and assesses the measures and indices of the endothelial functions and quantify the endothelial dysfunction of the target artery 108. The measurement module 204 comprises a local stiffness evaluation module 240, where data comprising the generated time-varying beat-by-beat end-diastolic diameter, distension, pressure, and related fiducial values from the cycle-analysis module 234 are communicated to the local stiffness-evaluation module 240. The local stiffness-evaluation module 240 evaluates and assesses the local stiffness indices of the target artery 108 based on the received data.

In other words, based on Figure 2, the image-free augmented multimodal system 100 is positioned on the target artery 108 and the image-free augmented multimodal system 100 includes the integrated multimodal probe 102 that uses the ultrasound transducer 110 and the pressure sensor 112 for the simultaneous measurement of vascular dimensions and arterial pressure. The measurement from the pressure sensor 112 is communicated to the pressure wave detector and arterial pressure monitor 206, which converts the detected measurement into a signal that is communicated to the microcontroller 208. Secondly, the ultrasound transducer 110 is in communication with a high voltage pulser-receiver 218 via a transmitter/receiver (Tx/Rx) switch 212. The Tx/Rx Switch 212 connects the ultrasound transducer 110 to a transceiver (Tx/Rx) 216. The ultrasound transducer 110 is positioned on the target artery 108, as shown in Figure 1 and ultrasound is used to assess the local arterial dimensions of that artery. A high voltage generation module 218 works in combination with the transceiver 216 to generate high-voltage excitation pulses and receive a signal from the ultrasound transducer 110 that is associated with the dynamic motion of the artery/surrounding structure and the local arterial dimension of that artery 108. During the operation, a microcontroller 208 communicates with the transceiver 216 and Tx/Rx Switch 212. These modules control the ultrasound transducer 110 while transmitting and receiving ultrasound echo signals. The received ultrasound echo signal is fed to the microcontroller 208.

In a first case, the microcontroller 208 communicates the ultrasound frames that are based on the information detected by the ultrasound transducer 110, to an automatic artery wall recognition module 220, which detects the locations of the wall. The automatic artery wall recognition module 220 then communicates the information of the detected wall to the automatic wall tracking module 222, where the wall motion profile is tracked. The tracked profile of the wall is communicated to the diameter-distension evaluation module 224 that generates the diameter and distension waveform based on the tracked motion/vibration of the wall. In a second case, the microcontroller 208 communicates pressure pulse waves to an arterial pressure wave module 226, which derives an arterial pressure waveform out of the pressure pulse waves. The derived arterial pressure waves are communicated to a processing module 228 that processes the derived waveform and the processing module 228 communicates the information to a pressure-value-and-waveform extraction module 230 that generates a set of arterial pressure values and a corresponding pressure waveform.

Both the information from modules 224 and 230 containing the diameter/distension waveform and the arterial pressure values/pressure waveforms respectively, are communicated to a cyclecutting module 232, which is communicated to a cycle-analysis module 234 that generates time-varying beat-by-beat end-diastolic diameter, distension, pressure, and related fiducial values. The cycle-analysis module 234 communicates the information to a cycle- segregation module 236 that segregates values for baseline state, low flow state, and vasodilation state, which is then communicated to the range-analysis module 238 that generates baseline, peak, and recovery values for each cardiac cycle. The range-analysis module 238 communicates the information to endothelial function-evaluation module 242 that performs the assessment of endothelial function and quantify its dysfunction. The information regarding local stiffness indices is directly generated in the local stiffness-evaluation module 240 from the information that is communicated directly from cycle-analysis module 234.

The endothelial function-evaluation module 242 measures various in-vivo markers of the artery’s endothelial function including AFMD (peak change in brachial artery diameter in response to reactive hyperaemia or an excitation produced by intervention and reactivity), % AFMD, and vascular reactivity. These markers are evaluated using information communicated directly from cycle-analysis module 234, which includes calculation of absolute value, peak change, relative change, rate of change, gradient, and strain in dimensions of a target artery.

The endothelial function-evaluation module 242 further gives augmented multimodal measurements of endothelial function, vascular structure, and vascular function over continuous cardiac cycles. Module 242 generates values of individual cardiac cycles and their average. These measurements include (not limited to) absolute value, peak change, relative change, rate of change, and gradient in (1) arterial structural dimensions, (2) transmural pressure, luminal pressure, and mechanical stress experienced by the target artery, (3) material properties of the target artery, and (4) static and dynamic responses of the target artery. Structural dimensions, estimates of arterial pressure, material properties (such as hyperelasticity, viscoelasticity, distensibility, specific stiffness, compliance, incremental elasticity, and elastin-collagen interaction, Windkesselness, characteristic impedance, conductivity), and static and dynamic vascular measurements (such as pulse pressure amplification, pulse wave velocity, augmented pressure, augmentation index, intima-media thickness, subendocardial viability ratio, ejection duration) are evaluated using information communicated directly from cycle-analysis module 234 before and after a controlled in-vivo excitation produced by intervention and reactivity.

The local stiffness evaluation modules 240, on the other hand, gives material properties of a small segment of the target artery in terms of compliance and distensibility for vascular health assessment. The local stiffness markers evaluated by 240 includes, but not limited to, specific stiffness index, arterial compliance, arterial distensibility, pres sure- strain elastic modules, incremental elastic modulus, pulse wave velocity, and incremental pulse wave velocity.

As will be appreciated by one of skill in the art, the present disclosure may be embodied as a method and system. Accordingly, the present disclosure may take the form of entirely hardware embodiment, a software embodiment or an embodiment combining software and hardware aspects.

It will be understood that the functions of any of the units, as described above, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general-purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts performed by any of the units as described above.

Instructions may also be stored in a computer-readable memory that can direct a computer or other programmable data processing apparatus to function in a particular manner, such that the instructions stored in the computer-readable memory produce an article of manufacture including instruction means which implement the function/act performed by any of the units as described above.

Instructions may also be loaded onto a computer or other programmable data processing apparatus like a scanner/check scanner to cause a series of operational steps to be performed on the computer or other programmable apparatus to produce a computer-implemented process such that the instructions which execute on the computer or other programmable apparatus provide steps for implementing the functions/acts performed by any of the units as described above.

In the specification, there have been disclosed exemplary embodiments of the invention. Although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes of limitation of the scope of the invention.

Claims

We claim:

1. An image-free augmented multimodal system for simultaneous, continuous, and real-time non-invasive assessment of vascular dimensions, arterial pressure, endothelial function, and local stiffness indices of a target artery, comprising: an integrated flow restrictor that controls blood flow through the target artery; an ultrasound transducer and a pressure sensor forming parts of one or more probes, wherein each probe is positioned in contact with the skin-tissue above the target artery, and wherein the ultrasound transducer generates signals based on the vascular dimensions, and the pressure sensor generates signals based on the arterial transmural pressure; a high voltage pulser-receiver in communication with the ultrasound transducer, wherein the high voltage pulser receiver excites the ultrasound transducer that sends ultrasound echo signals towards the target artery and transmit the received signals to a microcontroller; an arterial pressure wave detector is in communication with the pressure sensor to receive the arterial transmural pressure signals, wherein the arterial pressure wave detector converts the generated pressure signal into a pressure pulse wave that is communicated to the microcontroller, wherein the microcontroller generates a set of ultrasound frames based on the ultrasound echo signals and a pressure pulse wave based on the pressure sensor signal; and a measurement module controlled by at least one processor, wherein the measurement module is in communication with the ultrasound transducer and the pressure sensor to receive the ultrasound frames and the pressure pulse wave respectively, wherein the vascular dimensions, arterial pressure, endothelial function, and local stiffness indices of the target artery are determined by the measurement module based on an augmented multimodal analysis of the ultrasound frames and the pressure pulse wave.

2. The image-free augmented multimodal system as claimed in claim 1, wherein the high voltage pulser-receiver comprises: a transceiver; a transmitter-receiver switch that connects the ultrasound transducer to the transceiver; and a high voltage generation module that works in combination with the transceiver to generate high-voltage excitation pulses and receives a signal from the ultrasound transducer that is associated with dynamic motion of the target artery and arterial dimension of that target artery and wherein the microcontroller is in communication with the transceiver and the transmitter-receiver switch.

3. The image-free augmented multimodal system as claimed in claim 1, wherein the measurement module comprises an automatic artery wall recognition module, and wherein the microcontroller communicates the ultrasound frames that are based on the information detected by the ultrasound transducer to the automatic artery wall recognition module that recognises the locations of the artery walls.

4. The image-free augmented multimodal system as claimed in claim 3, wherein the measurement module comprises an automatic wall tracking module, wherein the automatic artery wall recognition module communicates the information of the recognised wall locations to the automatic wall tracking module that tracks the profile of the dynamic artery wall motion and vibrations.

5. The image-free augmented multimodal system as claimed in claim 4, wherein the measurement module comprises a diameter-distension evaluation module, and wherein the tracked profile of the artery walls is communicated to the diameter-distension evaluation module that generates a diameter and distension waveform based on the motion and vibration of the artery walls.

6. The image-free augmented multimodal system as claimed in claim 1, wherein the measurement module comprises an arterial pressure wave module, and wherein the microcontroller communicates the digitized pressure pulse wave to the arterial pressure wave module that derives a digital domain waveform from of the pressure pulse wave data communicated by the microcontroller.

7. The image-free augmented multimodal system as claimed in claim 6, wherein the measurement module comprises a processing module, wherein the derived digital domain waveform of the digitized pressure pulse wave is communicated to the processing module that processes the derived waveform.

8. The image-free augmented multimodal system as claimed in claim 7, wherein the measurement module comprises a pres sure- value-and- waveform extraction module, and wherein the processing module communicates the processed waveform to the pressure-value- and-waveform extraction module that extracts a set of pressure waveforms and corresponding arterial pressure values.

9. The image-free augmented multimodal system as claimed in claim 1, wherein the measurement module comprises a cycle-cutting module, wherein waveform data from the diameter-distension evaluation module and the pressure-value-and-waveform extraction module that includes the diameter with the distension waveform and the set of pressure waveforms with the corresponding arterial pressure values, are communicated to the cyclecutting module that performs synchronized automatic cycle cutting and selection of the waveform data for individual heartbeat over continuous cardiac cycles.

10. The image-free augmented multimodal system as claimed in claim 9, wherein the measurement module comprises a cycle-analysis module that receives the processed waveform data for the individual heartbeats over the continuous cardiac cycles from the cycle-cutting module and analyses the processed waveform data to generate time-varying beat-by-beat end- diastolic diameter, distension, and pressure values of the target artery.

11. The image-free augmented multimodal system as claimed in claim 10, wherein the measurement module comprises a cycle- segregation module, wherein the cycle-analysis module transmits the generated time-varying beat-by-beat end-diastolic diameter, distension, and pressure values to the cycle-segregation module, which segregates the beat-to-beat values for the baseline and intervened physical-physiological states, constituting baseline state, low flow state, and vasodilation state

12. The image-free augmented multimodal system as claimed in claim 11, wherein the measurement module comprises a range-analysis module that receives the segregated values for the physical-physiological states, constituting baseline state, low flow state, and vasodilation state, and wherein the range-analysis module generates baseline, minimum, peak, and recovery values of end-diastolic diameter and the corresponding distension and pressure based on the segregated beat-to-beat diameter, distension, and pressure values.

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13. The image-free augmented multimodal system as claimed in claim 12, wherein the measurement module comprises an endothelial function-evaluation module, and wherein the range-analysis module communicates the generated baseline, minimum peak, and recovery values of end-diastolic diameter and the corresponding distension and pressure to the endothelial function-evaluation module that evaluates and assesses the measures and indices of the endothelial functions and quantify endothelial dysfunction of the target artery.

14. The image-free augmented multimodal system as claimed in claim 13, wherein the endothelial function-evaluation module generates augmented multimodal measurements of endothelial function, vascular structure, and vascular function over continuous cardiac cycles, wherein values of individual cardiac cycles and their average comprise: absolute value, peak change, relative change, rate of change, and gradient in structural dimensions of the target artery in response to excitation produced by intervention and reactivity; absolute value, peak change, relative change, rate of change, and gradient in transmural pressure, luminal pressure, and mechanical stress of the target artery in response to excitation produced by the intervention and the reactivity, absolute value, peak change, relative change, rate of change, and gradient in material properties of the target artery in response to excitation produced by the intervention and the reactivity, and absolute value, peak change, relative change, rate of change, and gradient in static and dynamic responses of the target artery to excitation produced by the intervention and the reactivity.

15. The image-free augmented multimodal system as claimed in claim 10, wherein the measurement module comprises a local stiffness evaluation module, wherein data comprising the generated time-varying beat-by-beat end-diastolic diameter, distension, and pressure values from the cycle-analysis module are communicated to the local stiffness-evaluation module that evaluates and assesses the local stiffness indices of the target artery based on the received data.

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16. A method for simultaneous, continuous, and real-time non-invasive assessment of vascular dimensions, arterial pressure, endothelial function, and local stiffness indices of a target artery, the method comprising: controlling blood flow through the target artery via an integrated flow restrictor; positioning one or more probes in contact with the skin-tissue above the target artery; sending ultrasound echo signals towards the target artery via an ultrasound transducer in communication with a high voltage pulser- receiver; generating ultrasound echo signals based on the vascular dimensions via an ultrasound transducer that is positioned in one of the probes; generating pressure signals based on the arterial transmural pressure via a pressure sensor that is positioned in another one of the probes; transmitting the received ultrasound echo signals to a microcontroller in communication with the ultrasound transducer; converting the generated pressure signal into a pressure pulse wave that is communicated to the microcontroller via an arterial pressure wave detector in communication with the pressure sensor; generating a set of ultrasound frames based on the ultrasound echo signals and a pressure pulse wave based on the pressure sensor signal via the microcontroller; and determining the vascular dimensions, arterial pressure, endothelial function, and local stiffness indices of the target artery by a measurement module controlled by at least one processor, based on the ultrasound frames and the pressure pulse wave that are received from the ultrasound transducer and the pressure sensor respectively.

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