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.

Wearable Ambulatory Accelerometer System for Estimating Arterial Stiffness: A Pilot Study.

Given the gap between the crucial role of measuring arterial stiffness in cardiovascular disease prevention and the lack of a technology for frequent/continuous measurement to assess it without an operator, we have developed a wearable accelerometer-based system. It estimates local stiffness metrics (Ep, ß, and AC) by employing a one-point patient-specific calibration on the features of acceleration plethysmogram (APG) signal. An in-vivo study on 12 subjects was conducted (a) to select suitable ones from the host features on which the calibration could be applied and (b) to assess the feasibility of reliably estimating the stiffness metrics post-exercise when calibrated prior. The acquired APG signals were found to be reliable (SNR > 38 dB) and repeatable (CoV < 10 %). By examining a correlation matrix, it was found that (a-b)/(a"-b") is a potential feature of consideration for calibration against the stiffness. Due to exercise intervention, the local stiffness metrics have physiologically perturbed by a significant amount (p < 0.05), as observed from the reference measurements. Estimated Ep was found to have statistically significant and strong correlation (r = 0.761, p < 0.05) with actual Ep value, whereas statistically significant and moderate correlation were found with estimated ß (r = 0.682, p < 0.05) and estimated AC (r = 0.615, p < 0.05) with their respective actual measures. The system demonstrated its ability to estimate post-exercise stiffness metrics using the baseline calibration, even when subject to significant physiological changes.Clinical Relevance- This study reveals the potential of the developed wearable system to be used for continuous stiffness estimation even in the presence of hemodynamic perturbations.

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.

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.

Normalization of Flow-mediated Dilation to Brachial Artery Material Property: A Feasibility Study.

Endothelial reactivity (ER) is widely measured using flow-mediated dilation (FMD) of brachial artery. Conventional measurement of FMD is influenced by factors such as input shear stress, arterial transmural pressure, diameter and thereby arterial material properties (ε). Thus, for a reliable interpretation of FMD, it has to be normalized with respect to the above confounding factors. Normalization of FMD with shear stress at the time of measurement has been reported to reduce measurement variability. However, its widespread usage among the research community is limited. In this work, we examine the feasibility of normalizing the brachial FMD index (FMD%) to ε : extrema (εp), baseline (εb) and extrema change (∆ε) post-ischemia using its inter-day variability against FMD. In-vivo measurements were performed on 10 participants for 2 consecutive days and simultaneous pressure-diameter cycles were collected to estimate the material properties during reactive hyperemia (RH). The box-whisker plot reveals differences in the mean and deviation of FMD to FMD|εb. A significant value for repeatability (ICC ≥ 0.6) was obtained for normalized FMD (FMD|εb) for specific stiffness index (ß), pressure-strain elastic modulus (Ep), and local pulse wave velocity (PWV) as compared to FMD. Hence, normalization of FMD% to arterial ε can potentially improve the measurement reliability of ER assessment.Clinical Relevance- This pilot study demonstrates the feasibility of brachial artery stiffness assessment during FMD and its potential use for normalizing the standard FMD measurement.

Plethysmograph-Based Self-Assessment Device for Carotid-Femoral Pulse Wave Velocity Measurement: A Pilot Usability Study.

Arterial stiffness, a proxy of vascular aging is an important marker of cardiovascular events and mortality, independent of traditional risk factors. The aortic or carotid-femoral pulse wave velocity (cf-PWV) is the gold standard for determining arterial stiffness. Measuring arterial stiffness can help identify people who are at risk early on. State-of-the-art devices, majorly employing applanation tonometry at the carotid site, demand extensive skill, are costly, and are not intended for out-of-clinic use. However, a device that is suitable for homecare and primary health settings would facilitate primordial care. To address this gap, we have developed a novel easy-to-use, fully automated, and affordable photoplethysmography-based device for measuring cf-PWV. An in-vivo study on 25 subjects was conducted to investigate the device's usability by comparing self and expert-performed measurements, and by quantifying the user experience (score out of 5). A strong correlation (r = 0.88) and a statistically insignificant bias indicated the measurement reproducibility in self-versus expert-performed measurements. An average usability score of 3.98 ± 0.83 given by the participants showed the convenience and ease of use of the device. The results demonstrate the feasibility and reliability of using the device by inexperienced operators, even when newly introduced. Future clinical studies are in progress to assess the device's accuracy in comparison to gold-standard reference equipment.Clinical Relevance-This pilot study revealed the device's potential to offer a user-friendly solution for home care and other non-hospital settings.

Operator Variabilities in Carotid Pulse Wave Velocity Measured by an Image-free Ultrasound Device.

Local pulse wave velocity (PWV) has gained much attention in the last decade due to its ability to provide localized stiffness information from a target vessel and cater to several applications beyond regional PWV. Transit time-based methods are the most straightforward, but their reliability is highly dependent on the blood pulse sensing modality. Conventional ultrasound systems directly measure the blood pulse (as diameter or flow velocity); however, they offer limited frame rates resulting in poor resolution signals. Advanced systems supporting high frame rates are expensive, complex, and not amenable to field and resource-constraint settings. We have developed a high frame image-free ultrasound system to address this gap for automated and online measurement of local PWV. In an earlier in-vitro study, we have demonstrated its accuracy. In this work, we aim to investigate its in-vivo reliability. A study on 15 young, healthy subjects was conducted to assess the intra-and inter-operator repeatability of the developed system. The yielded local PWVs from the left carotid artery were within the range of 2.5 to 5.8 m/s. The device provided highly repeatable intra- and inter-operator measurements with ICC of 0.94 and 0.88, respectively. The bias for the intra- and inter-operator trials was statistically negligible (p > 0.005). The study demonstrated the potential of the high frame rate device to perform reliable measurements in-vivo. Clinical Relevance- This work aims to provide and validate an easy-to-use affordable and fully-automated high frame rate ultrasound technology for the measurement of online local PWV that is currently lacking.

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.

Evaluation of Vascular Pulse Contour Indices over the Physiological Blood Pressure Ranges in an Anesthetized Porcine Model.

A series of physiological measures can be assessed from the arterial pulse waveform, which is beneficial for cardiovascular health diagnosis, monitoring, and decision making. In this work, we have investigated the variations in regional pulse wave velocity (PWVR) and other pulse waveform indexes such as reflected wave transit time (RWTT), augmentation index (Alx), ejection duration index (ED), and subendocardial viability ratio (SEVR) with blood pressure (BP) parameters and heartrate on a vasoconstrictor drug-induced porcine model. Two healthy female (nulliparous and non-pregnant) Sus scrofa swine (~ 80 kg) was used for the experimental study. The measurement system consists of a catheter-based system with two highly accurate pressure catheters placed via the sheath at the femoral and carotid artery for acquiring and recording the pressure waveforms. The pulse waveform indexes were extracted from these recorded waveforms. Results from the pulse contour analysis of these waveforms demonstrated that Phenylephrine, as a post-synaptic alpha-adrenergic receptor agonist that causes vasoconstriction, produced a significant increment in the carotid BP parameters and heartrate. Due to the drug's effect, the PWVR and SEVR were significantly increased, whereas the RWTT, AIx index and ED index significantly decreased.Clinical Relevance- This experimental study provides the usefulness of the pulse contour analysis and estimation of various pulse waveform indexes for cardiovascular health screening and diagnosis.

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.