Ultrasound for Venous Local Pulse Wave Velocity: Comparison of Pulse Transit Time Methods.

Venous pulse wave velocity (vPWV) is a potential marker for determining the state of venous hemodynamics, venosclerosis, and vascular filling. Although there have been several studies on pulse wave velocity through blood vessels, the majority have focused on arteries, with only limited studies on veins. To our knowledge, this study is the first to compare the local vPWV estimation metrices. An in vivo study was conducted on 10 participants where the jugular venous pulses (JVP) from two proximal sites were simultaneously acquired using a dual-element high frame rate system. The local vPWV was computed using different transit time-based techniques. The study demonstrates the comparison between vPWV ranges computed using thresholding, fiduciary point (c and v) and correlation-based approaches indicated as vPWV|th, vPWV|c, vPWV|v and vPWV|Xcorr respectively. High fidelity echo frames were acquired from the jugular vein (JV) at a temporal resolution of 2 ms and an amplitude resolution of 10 µm. The study findings indicated that the vPWV computed using various transit time metrics were comparable without significant bias (p > 0.05). Among the VPWV metrices, vPWV|th had the lowest beat-to-beat variation (CoV = 18 %). The mean deviations in vPWV|c, vPWV|v and vPWV|Xcorr values from vPWV|th were 0.28, 0.17 and 0.22 m/s respectively, where the average beat-to-beat variation was minimal. The results suggested that the thresholding and cross-correlation metrices offered better performance in comparison with the fiduciary point techniques for vPWV estimation.Clinical Relevance- The study demonstrated the potential of direct transit time methods to reliably estimate the local vPWV on the internal jugular vein.

Arterial Wave Separation Analysis and Reflection Wave Transit Time Estimation using a Double Rayleigh Flow Rate Model.

Arterial pulse wave separation analysis (WSA) requires simultaneously measured pressure and flow rate waveform from the same arterial site. Modelling approaches to flow rate waveforms offers a methodological and instrumentational advantage. However, current techniques are limited to the aortic site. For non-aortic sites such as carotid artery, modelling methods that were developed for aortic sites are not likely to capture the intrinsic differences in the carotid flow rate. In this work, a double-Rayleigh flow rate model for the carotid artery is developed to separate the forward and backward pressure waves using WSA (DRMWSA). The model parameters are optimally found based on characteristic features - obtained from the pressure waveform. The DRMWSA was validated using a database of 4374 virtual (healthy) subjects, and its performance was compared with actual flow rate based WSA (REFWSA) at the carotid artery. An RMSE < 2 mmHg were obtained for forward and backward pressure waveforms. The reflection quantification indices (ΔPF, ΔPB), (RM, RI) obtained from DRMWSA demonstrated strong and statistically significant correlation (r > 0.96, p < 0.001) and (r > 0.80, p < 0.001) respectively, with insignificant bias (p > 0.05), upon comparing with counterparts in REFWSA. A moderate correlation (r = 0.64, p < 0.001) was obtained for reflection wave transit time between both methods. The proposed method minimises the measurements required for WSA and has the potential to widen the vascular screening procedures incorporating carotid pulse wave dynamics.Clinical Relevance-This methodology quantifies arterial pressure wave reflections in terms of pressure augmentation and reflection transit time. The methodological advantage of using only a single waveform helps easy translation to technological solutions for clinical research.

Assessment of Endothelial Reactivity by Measurement of Vascular Material Response to Shear Stress: A Feasibility Study.

Flow-mediated dilation (FMD) evaluates the relative change in arterial diameter during hyperemia to assess the endothelial response due to a shear stimulus. However, conventional FMD measures diameter response alone and the alterations in the arterial wall's material properties during reactive hyperemia, which also influence dilation, go unaddressed. In this work, we examine the material response (MR) of the artery during reactive hyperemia using clinically relevant stiffness markers for the assessment of endothelial reactivity (ER). For this, we have developed an in-house brachial cuff control (BCC) system to continuously acquire brachial pressure which can be integrated with simultaneous measurement of brachial diameter and used to quantify the relative changes in wall property during hyperemia non-invasively. The assessment of endothelial reactivity using material response (ERAMR) was conducted on 20 healthy participants (12M/8F) and the results were compared with conventional FMD (FMD%). The mean pressure response gave an inverse trend to that of diameter response with varying magnitudes during reactive hyperemia (18.71% from baseline for diameter and 2.45% for pressure), there was a significant difference in the measurement of FMD and ERAMR (P < 0.05). The larger distribution of ERAMR compared to FMD% in box-plots further implies the inclusion of within-subject variations. Hence, ERAMR can be a potential estimate of ER, given the need for intensive validations in this line on larger cohorts.Clinical Relevance- This study demonstrates the independent role of arterial wall material properties to quantify endothelial reactivity in response to a shear stimulus.

A Pilot Observational Cohort Study to Investigate the Effect of Valsalva Maneuver on Internal Jugular Venous Diameter.

Valsalva maneuver (VM) is a technique widely used for acute elevation of blood pressure in humans. It has potential applications in cardiac health prediction and is also a diagnostic tool in cardiovascular, neurology and ENT screening. The jugular venous (JV) diameter increases during the VM procedure and hence it has been widely used to aid central venous catheterization in medical units. In this pilot study, we have quantified the variation in JV diameter response to VM across young and middle-aged populations. The study was conducted on a cohort of 16 males and 11 females, where the JV diameter in baseline, during and post VM intervention were acquired using a B-mode imaging system. The JV diameter measurements were within the ranges specified in earlier literature. The beat-to-beat variability in baseline diameter measurements was found to be between 8% to 20%. In younger population, the average maximum JV diameter during baseline was found to be 9.25 ± 2.61 mm and in middle-aged population it was 12.49 ± 2.65 mm. The average maximum JV diameter in young and middle-aged population during VM was 11.66 ± 2.74 mm and 16.73 ± 3.28 mm respectively. The study findings suggested a statistically significant variation (p < 0.05) between the JV diameter responses from young and middle-aged populations. The JV distensibility decreased significantly during VM in younger cohort (-35%) in comparison with the minimal changes observed in middle-aged population. The study demonstrates the variation in JV diameter and distensibility to VM in young and middle-aged populations.Clinical Relevance- This pilot study reveals the variations in JV diameter in response to VM intervention in young and middle-aged groups which has potential utility in assessing age dependent changes in vasculature.

Comparison of Approximated and Actual Bramwell-Hill Equation Implementation for Local Pulse Wave Velocity: Ex-vivo Study.

Bramwell-Hill (BH) equation is widely adopted for the evaluation of local pulse wave velocity (PWV), primarily for its theoretical association with the vessel's distensibility. Its implementation, however, requires arterial pressure and diameter waveforms simultaneously from a single site. Owing to the challenges associated with such a noninvasive recording, an approximated BH equation is adopted without requiring the entire pressure waveform but only the diastolic and systolic values. The approximated BH method yields a single value of local PWV as opposed to the actual method that provides instantaneous PWV within a cardiac cycle. This study aims to provide the currently lacking insights into how the approximate versus actual BH implementations compare. The study also addresses the pivotal question of which instantaneous value within the cardiac cycle corresponds to the approximated BH. An ex-vivo study was conducted for this purpose, emulating different flow conditions (changing mean and pulse pressures) to vary the local PWV within the range of 4.4 to 8.9 m/s. The results revealed the expected (pressure-dependent) incremental nature of local PWV due to hyper-elastic behavior of the artery, with systolic BH-PWV > diastolic BH-PWV by 13.6%. The approximate BH-PWV was similar to actual BH-PWV obtained from mean pressure level. It further underestimated the systolic, and overestimated the diastolic PWVs by 8.5% and 6.6%, respectively. Clinical Relevance - When estimated BH-PWV estimates are compared to normal values for patient classification or utilized as a reference standard in validation studies these findings become extremely important.

Gaussian-Mixture Modelling of A-Mode Radiofrequency Scans for the Measurement of Arterial Wall Thickness.

Measurement of arterial wall thickness is an integral component of vascular properties and health assessment. State-of-the-art automated or semi-automated techniques are majorly applicable to B-mode images and are not available for entry-level in-expensive devices. Considering this, we have earlier developed and validated an image-free (A-mode) ultrasound device, ARTSENS® for the evaluation of vascular properties. In this work, we present a novel gaussian-mixture modeling-based method to measure arterial wall thickness from A-mode frames, which is readily deployable to the existing technology. The method's performance was assessed based on systematic simulations and controlled phantom experiments. Simulations revealed that the method could be confidently applied to A-mode frames with above-moderate SNR (>15 dB). When applied to A-mode frames acquired from the flow-phantom setup (SNR > 25 dB), the mean error was limited to (2 ± 1%), and RMSE was 19 µm, on comparison with B-mode measurements. The measured and reference wall thickness strongly agreed with each other (r = 0.88, insignificant mean bias = 7 µm, p = 0.16). The proposed method was capable of performing real-time measurements.

High-Framerate A-Mode Ultrasound for Vascular Structural Assessments: In-Vivo Validation in a Porcine Model.

Capturing vascular dynamics using ultrasound at a high framerate provided a unique way to track time-dependent and transient physiologic events non-invasively. In this work, we present an A-model high-framerate (500 frames per second) image-free ultrasound system for monitoring vascular structural and material properties. It was developed based on our clinically validated ARTSENS® technology. Following in-vitro verification on arterial flow phantoms, its measurement accuracy and high-framerate data acquisition and processing were verified in-vivo on 2 anesthetized Sus scrofa swine. Measurements of the carotid artery (the luminal diameter, distension, and wall thickness) obtained using the high-framerate system were comparable to those provided by a clinical-grade reference ultrasound imaging device (absolute error < 4%, < 6.3%, and < 6.6%, respectively). Notably, the morphology of the arterial distension waveforms obtained at high-framerate depicted vital physiological fiduciary points compared to the low-framerate reference waveform. The compression-decompression pattern of the arterial wall was also captured with the high-framerate system, which is challenging with low-framerate ultrasound. Potential applications of these high temporal structural waveforms have also been discussed.

Phantom Assessment of an Image-free Ultrasound Technology for Online Local Pulse Wave Velocity Measurement.

Cardiovascular community has started clinically adopting the assessment of local stiffness, contrary to the traditionally measured carotid-femoral pulse wave velocity (PWV). Though they offer higher reliability, ultrasound methods require advanced hardware and processing methods to perform real-time measurement of local PWV. This work presents a system and method to perform online PWV measurement in an automated manner. It is a fast image-free ultrasound technology that meets the methodological requirements necessary to measure small orders of local pulse transit, from which PWV is measured. The measurement accuracy and repeatability were assessed via phantom experiments, where the measured transit time-based PWV (PWVTT) was compared against the theoretically calculated PWV from Bramwell-Hill equation (PWVBH). The beat-to-beat variability in the measured PWVTT was within 3%. PWVTT values strongly correlated (r=0.98) with PWVBH, yielding a negligible bias of -0.01 m/s, mean error of 3%, and RMSE of 0.27 m/s. These pilot study results demonstrated the presented system's reliability in yielding online local PWV measurements.

Cuffless Blood Pressure Estimation Using Features Extracted from Carotid Dual-Diameter Waveforms.

The major challenges in deep learning approaches to cuffless blood pressure estimation is selecting the most appropriate representative of the blood pulse waveform and extraction of relevant features for data collection. This paper performs an analysis of a novel dataset consisting of 71 features from the carotid dual-diameter waveforms and 4 blood pressure parameters. In particular, the analysis uses gradient boosting and graph-theoretic algorithms to determine (1) features with high predictive power and (2) potential to be pruned. Identifying such features and understanding their physiological significance is important for building blood pressure estimation models using machine learning that is robust across diverse clinical environments and patient sets.

Demonstration of Pressure-Dependent Inter and Intra-Cycle Variations in Local Pulse Wave Velocity Using Excised Bovine Carotid Artery.

Pulse wave velocity (PWV) is a function of the artery's material property, and its incremental nature in elastic modulus led to the concept of incremental PWV. Recent advancements in technology paved the way for reliable measurement of the variation in PWV within a cardiac cycle. This change in PWV has shown its potential as a biomarker for advanced cardiovascular diagnostics, screening, and has recently started using as a vascular screening tool and medical device development. In this work, we have demonstrated the concept of inter and intra-cycle variations of PWV with pressure using an excised bovine carotid artery. Results demonstrated that local PWV measured at the foot of the waveform followed the same trend as of the pressure. As the pressure level was increased to 68% across the cycles, resulting PWV increased up to 81%. An exponential PWV-Pressure relationship was obtained, in agreement with the widely used models. The incremental nature of PWV was recorded in a reflection-free region of the pressure pulse wave. This was further demonstrated in continuous pulse cycles with varying pressure ranges, by comparing the PWV values at two fiduciary points selected in the upstroke of the pressure wave. On average, a 48.11% increase in PWV was observed for 31.04% increase in pressure between the selected fiducial points within a pulse cycle. The article concludes, highlighting the clinical significance of incremental PWV.Clinical Relevance- This experimental study supplements the evidence for the incremental nature of PWV within a cardiac cycle, which has the potential for being a biomarker for advanced cardiovascular screening and diagnostics.

High-Throughput Vascular Screening by ARTSENS Pen During a Medical Camp for Early-Stage Detection of Chronic Kidney Disease.

Intervention in the early stages of cardiovascular and kidney diseases is proven to be more effective in preventing disease progression. Large artery stiffness measurement can be a potential early predictor of future risks. The purpose of the study reported in this work was to demonstrate the feasibility of our ARTSENS® Pen device as a high-throughput vascular screening tool for risk assessment. The study was performed during a medical camp conducted for awareness and early-stage detection of kidney diseases. Screening procedures included biosample tests and blood pressure measurements. Alongside, various clinically relevant measures of the arterial stiffness were evaluated using the ARTSENS® Pen, by measuring vessel wall dynamics via our proprietary image-free ultrasound algorithms. Stiffness measurement from the left common carotid artery on 85 participants could be completed within 4 hours, employing two units of ARTSENS® Pen; this also includes time taken for all the procedures enlisted in the study protocol. The associations of carotid stiffness indices with age-, gender-, and risk factor-dependent variations were established.

Novel Geometric Representation for One-Dimensional Model of Arterial Blood Pulse Wave Propagation.

This paper proposes a novel one-dimensional graphical representation to model the phenomenon of blood pulse wave propagation in major arteries. In particular, a tree data structure, as opposed to the existing purely linear structures, is used to accommodate arterial branching. The model is qualitatively validated and its demonstrated reliability by evaluating the phenomenon of wave reflection and pulse pressure amplification with a sample in-vivo arterial segment length measurements.

Multimodal Image-Free Ultrasound Technique for Evaluation of Arterial Viscoelastic Properties: A Feasibility Study.

In this article, we have presented a multimodal system and a novel probe design that was built around an image-free ultrasound technology, ARTSENS®, for measurement of arterial viscoelastic properties. ARTSENS® was extensively validated over the years, for performing measurements of arterial wall dynamics and stiffness with an accuracy that meets clinical standards. Concerning this work, several enhancements were incorporated to this basic technology that allowed high frame rate A-scan imaging (1 kHz) and integration of a pressure measuring module for automated measurements of the viscoelastic parameter (elastic index, viscous index and wall buffering function). The functionality of the developed multimodal system and probe were investigated by conducting an in-vivo on 8 young subjects (both normotensive and hypertensive were included). The beat-to-beat measurements of the viscoelastic parameters exhibited acceptable repeatability with a variability <; 6.5%. It was observed that the group average for viscosity index and the wall buffering function were higher for hypertensive subjects as compared to normotensive subjects. The study observations were consistent with the reported literature. The proposed system addresses several issues associated with the traditional image-based systems and offers huge advantage of field amenability thus making it favorable for large population screening and studies.

Arterial compliance probe for cuffless evaluation of carotid pulse pressure.

OBJECTIVE: Assessment of local arterial properties has become increasingly important in cardiovascular research as well as in clinical domains. Vascular wall stiffness indices are related to local pulse pressure (ΔP) level, mechanical and geometrical characteristics of the arterial vessel. Non-invasive evaluation of local ΔP from the central arteries (aorta and carotid) is not straightforward in a non-specialist clinical setting. In this work, we present a method and system for real-time and beat-by-beat evaluation of local ΔP from superficial arteries-a non-invasive, cuffless and calibration-free technique. METHODS: The proposed technique uses a bi-modal arterial compliance probe which consisted of two identical magnetic plethysmograph (MPG) sensors located at 23 mm distance apart and a single-element ultrasound transducer. Simultaneously measured local pulse wave velocity (PWV) and arterial dimensions were used in a mathematical model for calibration-free evaluation of local ΔP. The proposed approach was initially verified using an arterial flow phantom, with invasive pressure catheter as the reference device. The developed porotype device was validated on 22 normotensive human subjects (age = 24.5 ± 4 years). Two independent measurements of local ΔP from the carotid artery were made during physically relaxed and post-exercise condition. RESULTS: Phantom-based verification study yielded a correlation coefficient (r) of 0.93 (p < 0.001) for estimated ΔP versus reference brachial ΔP, with a non-significant bias and standard deviation of error equal to 1.11 mmHg and ±1.97 mmHg respectively. The ability of the developed system to acquire high-fidelity waveforms (dual MPG signals and ultrasound echoes from proximal and distal arterial walls) from the carotid artery was demonstrated by the in-vivo validation study. The group average beat-to-beat variation in measured carotid local PWV, arterial diameter parameters-distension and end-diastolic diameter, and local ΔP were 4.2%, 2.6%, 3.3%, and 10.2% respectively in physically relaxed condition. Consistent with the physiological phenomenon, local ΔP measured from the carotid artery of young populations was, on an average, 22 mmHg lower than the reference ΔP obtained from the brachial artery. Like the reference brachial blood pressure (BP) monitor, the developed prototype device reliably captured variations in carotid local ΔP induced by an external intervention. CONCLUSION: This technique could provide a direct measurement of local PWV, arterial dimensions, and a calibration-free estimate of beat-by-beat local ΔP. It can be potentially extended for calibration-free cuffless BP measurement and non-invasive characterization of central arteries with locally estimated biomechanical properties.

Bi-Modal Arterial Compliance Probe for Calibration-Free Cuffless Blood Pressure Estimation.

OBJECTIVE: We propose a calibration-free method and system for cuffless blood pressure (BP) measurement from superficial arteries. A prototype device with bi-modal probe arrangement was designed and developed to estimate carotid BP - an indicator of central aortic pressure. METHODS: Mathematical models relating BP parameters of an arterial segment to its dimensions and local pulse wave velocity (PWV) are introduced. A bi-modal probe utilizing ultrasound and photoplethysmograph sensors was developed and used to measure diameter values and local PWV from the carotid artery. Carotid BP was estimated using the measured physiological parameters without any subject- or population-specific calibration procedures. The proposed cuffless BP estimation method and system were tested for accuracy, usability, and for potential utility in hypertension screening, on a total of 83 subjects. RESULTS: The prototype device demonstrated its capability of detecting beat-by-beat arterial dimensions and local PWV simultaneously. Carotid diastolic BP (DBP) and systolic BP (SBP) were estimated over multiple cardiac cycles in real-time. The absolute error in carotid DBP was <10 mmHg in 82% cases, and root-mean-square-error = 8.3 mmHg. Consistent with the theory, estimated SBP at the carotid site was lower than the reference brachial SBP. ROC curves obtained for hypertension screening analysis revealed an area under the curve ≥0.8 for both carotid SBP and DBP values, illustrating the potential for using the developed method in hypertension screening. CONCLUSION: The feasibility of calibration-free, cuffless BP measurement at an arterial site of interest was demonstrated with a level of acceptable accuracy. The study also demonstrated the potential utility of the proposed method and system in hypertension screening and local evaluation of arterial stiffness indices. SIGNIFICANCE: Novel approach for calibration-free cuffless BP estimation; a potential tool for local BP measurement and hypertension screening.

A Magnetic Plethysmograph Probe for Local Pulse Wave Velocity Measurement.

OBJECTIVE: We present the design and experimental validation of an arterial compliance probe with dual magnetic plethysmograph (MPG) transducers for local pulse wave velocity (PWV) measurement. The MPG transducers (positioned at 23 mm distance apart) utilizes Hall-effect sensors and permanent magnets for arterial blood pulse detection. METHODS: The MPG probe was initially validated on an arterial flow phantom using a reference method. Further, 20 normotensive subjects (14 males, age = 24 ± 3.5 years) were studied under two different physical conditions: 1) Physically relaxed condition, 2) Postexercise condition. Local PWV was measured from the left carotid artery using the MPG probe. Brachial blood pressure (BP) was measured to investigate the correlation of BP with local PWV. RESULTS: The proposed MPG arterial compliance probe was capable of detecting high-fidelity blood pulse waveforms. Reliable local pulse transit time estimates were assessed by the developed measurement system. Beat-by-beat local PWV was measured from multiple subjects under different physical conditions. A profound increment was observed in the carotid local PWV for all subjects after exercise (average increment = 0.42 ± 0.22 m/s). Local PWV values and brachial BP parameters were significantly correlated (r ≥ 0.72), except for pulse pressure (r = 0.42). CONCLUSION: MPG arterial compliance probe for local PWV measurement was validated. Carotid local PWV measurement, its variations due to physical exercise and correlation with BP levels were examined during the in vivo study. SIGNIFICANCE: A novel dual MPG probe for local PWV measurement and potential use in cuffless BP measurement.