Jayaraj Joseph

Local pulse wave velocity (PWV) is evolving as one of the important determinants of arterial hemodynamics, localized vessel stiffening associated with several pathologies, and a host of other cardiovascular events. Although PWV was introduced over a century ago, only in recent decades, due to various technological advancements, has emphasis been directed toward its measurement from a single arterial section or from piecewise segments of a target arterial section. This emerging worldwide trend in the exploration of instrumental solutions for local PWV measurement has produced several invasive and noninvasive methods. As of yet, however, a univocal opinion on the ideal measurement method has not emerged. Neither have there been extensive comparative studies on the accuracy of the available methods. Recognizing this reality, makes apparent the need to establish guideline-recommended standards for the measurement methods and reference values, without which clinical application cannot be pursued. This paper enumerates all major local PWV measurement methods while pinpointing their salient methodological considerations and emphasizing the necessity of global standardization. Further, a summary of the advancements in measuring modalities and clinical applications is provided. Additionally, a detailed discussion on the minimally explored concept of incremental local PWV is presented along with suggestions of future research questions.

Objective: A novel photoplethysmograph probe employing dual photodiodes excited using a single infrared light source was developed for local pulse wave velocity (PWV) measurement. The potential use of the proposed system in cuffless blood pressure (BP) techniques was demonstrated. Approach: Initial validation measurements were performed on a phantom using a reference method. Further, an in vivo study was carried out in 35 volunteers (age = 28 ± 4.5 years). The carotid local PWV, carotid to finger pulse transit time (PTTR) and pulse arrival time at the carotid artery (PATC) were simultaneously measured. Beat-by-beat variation of the local PWV due to BP changes was studied during post-exercise relaxation. The cuffless BP estimation accuracy of local PWV, PATC, and PTTR was investigated based on inter- and intra-subject models with best-case calibration. Main results: The accuracy of the proposed system, hardware inter-channel delay (<0.1 ms), repeatability (beat-to-beat variation = 4.15%-11.38%) and reproducibility of measurement (r = 0.96) were examined. For the phantom experiment, the measured PWV values did not differ by more than 0.74 m s-1 compared to the reference PWV. Better correlation was observed between brachial BP parameters versus local PWV (r = 0.74-0.78) compared to PTTR (|r| = 0.62-0.67) and PATC (|r| = 0.52-0.68). Cuffless BP estimation using local PWV was better than PTTR and PATC with population-specific models. More accurate estimates of arterial BP levels were achieved using local PWV via subject-specific models (root-mean-square error 2.61 mmHg). Significance: A reliable system for cuffless BP measurement and local estimation of arterial wall properties.

Objective:The combined assessment of vascular health markers is crucial for identifying the cumulative burden of vascular risk factors early on, as well as the extent of vascular aging for effective prediction of future cardiovascular events. This work addresses the need for a currently nonexistent device or system that facilitates such combined assessment in clinical practice and large-scale screening settings. We report an image-free ultrasound device - ARTSENS Plus - developed for the measurement of local and regional arterial stiffness, central and peripheral blood pressure (BP), and vessel dimensions, all in one examination.Methods:A preclinical study on 90 asymptomatic individuals verified the device's functionality under ARTERY Society guidelines. The device's accuracy of stiffness measures was validated against the reference measures.Results:The interoperator and intraoperator variability was less than 7%. Carotid artery's lumen diameter and local stiffness indices and carotid-femoral regional pulse wave velocity showed excellent agreement with the references (absolute errors were less than 4.1, 9, and 4.1%, respectively). The carotid SBP was 10.02% lower than that of the brachial artery, as expected.Conclusion:The study demonstrated the device's ability to perform an effortless and reliable evaluation of the local and regional vascular stiffness and central BP with an accuracy that meets clinical standards.

Arterial stiffness (AS) has been shown to be an important marker for risk assessment of cardiovascular events. Local arterial stiffness (LAS) is conventionally measured by evaluating arterial distensibility at particular arterial sites through ultrasound imaging systems. Regional arterial stiffness (RAS) is generally obtained by evaluating carotid to femoral pulse wave velocity (cfPWV) through tonometric devices. RAS has a better prognostic value than LAS and cfPWV is considered as the gold standard of AS. Over the past few years our group has been developing ARTerial Stiffness Evaluation for Non-Invasive Screening (ARTSENS), an inexpensive and portable device to measure the LAS. It uses a single element ultrasound transducer to obtain A-Mode frames from the desired artery and is fully automated to enable a non-expert to perform measurements. In this work, we report an extension of ARTSENS to enable measurement of cfPWV that now makes it the only fully automatic device that can measure both LAS and RAS. In this paper, we provide a general review of the ARTSENS and compare it with other state-of-the-art AS measurement systems. cfPWV measurement using ARTSENS was cross-validated against SphygmoCor by successive measurements with both devices on 41 human subjects and excellent agreement between both devices was demonstrated (Coefficient of determination R2) = 0.70(p < 0.00001) and, limits of agreement (LoA) < 1.6 m/s). The inter-device correlation between ARTSENS and SphygmoCor was found to be better than other similar studies reported in the literature.

Reflections of arterial blood pulse waves have a pivotal role in the equilibrium of the vasculature. Elevated levels of wave reflections cause an increase in pulse pressure and pulse propagating speeds, exacerbating cardiovascular risk. Quantification of reflection markers is either based on augmentation index or reflection magnitude (RM) and reflection index (RI), both derived from wave separation analysis (WSA). Simultaneous measurement of pressure and flow velocity from the same arterial site is a requirement for WSA and has its practical challenges. Subsequently, simplified WSA based on modelling flow is proposed. This work explores the feasibility of using multi-Gaussian decomposition (MGD) of diameter scaled pressure waveform to perform a WSA and quantify the reflection markers. The diameter waveforms are obtained using an A-mode ultrasound device (ARTSENS®). The decomposed pressure signals scaled from diameter waveforms (or Gaussians) are uniquely combined to yield a forward and backward wave. The reflection markers derived from MGD based WSA are then compared with the clinically relevant stiffness markers and with age. The study was conducted on 110 healthy subjects (60 males and 50 females). A moderately significant correlation (mathrm{r} > 0.51,mathrm{p} < 0.001) was obtained for RM and RI when compared with stiffness markers (beta, Ep, AC, PWV and AIx). The highest correlation was observed for RM versus Ep (mathrm{r}= 0.602, mathrm{p} < 0.001), followed by beta and PWV. The correlation in reflection markers with age was captured with mathrm{r}=0.51, mathrm{p} < 0.001. A change of 25.2% and 15.4% were observed for the group average RM and RI, respectively, among normotensive and hypertensive subjects in this cohort. The proposed MGD model has the potential to explore the central arterial biomechanics from a diameter or pressure waveform. The variations in reflection markers with stiffness and age derived using the proposed WSA approach were faithfully captured. The flow-independent WSA, combined with a field-deployable measurement device like ARTSENS®, has the potential to conduct large scale vascular screenings in a resource-limited setting.

Objective: In this work, we demonstrate an accelerometric patch probe and associated measurement system for local pulse wave velocity (PWV) measurement and its application in cuffless blood pressure (BP) measurement. Approach: The proposed system consists of dual accelerometric patch probe to capture acceleration plethysmography (APG) signals from the carotid artery. The probe was integrated to an application-specific analog front-end circuitry with negligible inter-channel delay and a data acquisition module. Real-time signal processing and local PWV evaluation were performed using custom software. The functionality of the developed system and the relationship between local PWV and reference BP parameters were experimentally validated by multiple in vivo studies on a cohort of 26 subjects. Inter- and intra-subject BP-local pulse transit time (PTT) models were developed and used for cuffless BP measurement. Further, the reliability of the proposed method in long-term BP monitoring was validated by performing a study over a week. Main results: Reliability of the proposed novel approach for local PWV measurement using APG signals has been demonstrated. Measured baseline carotid local PWV values were in the range of 3-4.2 m s-1, with high reproducibility (R =0.94) and with an inter-beat variation range of 2.61%-15.5%. Mean local PTT versus brachial systolic, diastolic, and mean arterial BP obtained from both sitting and standing posture correlated well with an R-value >0.8. Beat-by-beat BP parameters and local PWV during the post-exercise recovery of each individual yielded statistically significant intra-subject trends. Cuffless BP estimation with intra-subject BP-local PTT models results in more reliable assessments of BP parameters than inter-subject models. The developed BP prediction models found to be reliable over a period of one week with a root-mean-square error ≤1.7 mmHg. Significance: A non-invasive cost-effective system for continuous monitoring central aortic BP parameters and local arterial stiffness indices.

Windkessel model assesses the buffering function of large arteries and has the potential to describe the global characteristics of the vasculature. In this work, we investigate the association between the Windkessel model parameters and the existing, clinically significant local, global stiffness indices and blood pulse indices. A three-element Windkessel model was used to estimate the ventricular-arterial coupling, arterial compliance, and peripheral resistance from the pressure and flow waveforms at the aorta. The study was performed on 213 healthy virtual subjects (age: 44 boldsymbol{pm15} years). Total arterial compliance had a significant individual correlation boldsymbol{(mathrm{R} > 0.50, mathrm{p}} boldsymbol{ < 0.05)} with local and regional stiffness indices whereas characteristic impedance had a correlation of boldsymbol{(mathrm{R} > 0.22, mathrm{p} < 0.05)} with stiffness indices. Total peripheral resistance, on the other hand, did not show a significant correlation with vascular stiffness. Multivariate regression gave a better independent correlation between the Windkessel model parameters and vascular indices (Adjusted boldsymbol{mathrm{R} > 0.88, mathrm{p} < 0.05)} with total peripheral resistance showing the highest correlation (Adjusted boldsymbol{mathrm{R}=0.95, mathrm{p} < 0.05)} and total arterial compliance showing with least correlation ( Adjusted boldsymbol{mathrm{R}=0.88, mathrm{p} < 0.05)}. The significance in the association of Windkessel markers with stiffness indices highlights the potential of Windkessel model parameters in being a prognostic marker for vascular ageing. The development of an instrumentation solution for the combined assessment of pressure and flow of central arteries would accelerate the applicability of Windkessel model parameters in field settings.

Objective: We investigate the field feasibility of carotid stiffness measurement using ARTSENS® Touch and report the first community-level data from India. Method: In an analytical cross-sectional survey among 1074 adults, we measured specific stiffness index (β), pressure-strain elastic modulus (Ep), arterial compliance (AC), and one-point pulse wave velocity (PWVβ) from the left common carotid artery. Data for established risk factors (waist circumference, blood pressure, plasma glucose, triglycerides, and HDL-C) were also collected. The association of carotid stiffness with age, gender, hypertension/diabetes, smoking, and clustering of risk factors was studied. Results: Measurements were repeatable with a relative difference (RD) between consecutive readings of < 5% for blood pressure and < 15% for ∼80% of arterial diameter values. The average RDs for β, Ep, AC, and PWVβ, were 20.51%, 22.31%, 25.10%, and 14.13%, respectively. Typical range for stiffness indices among females and males were β : 8.12 ± 3.59 vs 6.51 ± 2.78, Ep : 113.24 ± 56.12 kPa vs 92.33 ± 40.65 kPa, PWVβ : 6.32 ± 1.38 ms-1 vs 5.81 ± 1.16 ms-1, and AC: 0.54 ± 0.36 mm2 kPa-1 vs 0.72 ± 0.38 mm2 kPa-1. Mean β, Ep, and PWVβ increased (and mean AC decreased) across decades of age; the trend persisted even after excluding hypertensives and subjects with diabetes. The odds ratio of presence of multiple risk factors for Ep ≥ 93.71 kPa and/or PWV β≥6.56 ms-1 was ≥ 2.12 or above in males. In females, it was just above 2.00 for Ep ≥ 91.21 kPa and/or PWVβ ≥ 5.10 ms-1 and increased to ≥ 3.33 for Ep ≥ 143.50 kPa and ≥ 3.25 for PWVβ ≥ 7.31 ms-1. Conclusion: The study demonstrated the feasibility of carotid stiffness measurement in a community setting. A positive association between the risk factors and carotid artery stiffness provides evidence for the device's use in resource-constrained settings. Clinical Impact: The device paves the way for epidemiological and clinical studies that are essential for establishing population-level nomograms for wide-spread use of carotid stiffness in clinical practice and field screening of 'at-risk' subjects.

The modulated magnetic signature based method has been recently suggested for non-invasive detection of blood pulse. Here we present our experience with the use of a Giant Magnetic Resistance (GMR) based sensor for non-invasive detection of a bio-rhythm. The influence of the biasing magnetic field on the amplitude and shape of the detected signal is presented. Guidelines for the design of a bio-medical transducer using the principle are also provided. The detected biorhythm is compared to other bio signals such as the blood flow velocity and arterial distension to gain insight into the physiological significance of the detected signal. The analysis shows that the magnetic sensor provides a signal that is strongly correlated to the blood volume in the neighbourhood of the sensor. Finally, the possibility of using the GMR based sensor for estimation of arterial compliance is investigated. Simultaneous measurements performed at two different sites on the body show that this sensor can be used to measure arterial pulse wave velocity which is a clinically accepted measure of global arterial stiffness. © 2010 IEEE.

The paper describes a non-invasive method using an accelerometric system with a patch probe for arterial stiffness monitoring based on the estimation of the reflected wave transit time (RWTT). The study aims to validate the designed accelerometric system based on RWTT by comparison with currently used ultrasound-based imaging techniques. The proposed system consists of an accelerometric probe with a MEMS acceleration sensor fabricated on a flexible PCB for continuous monitoring of surface acceleration plethysmogram (APG) from the carotid arterial site. An analog front-end circuitry was designed for the reliable acquisition of APG signal and its pre-processing. The acquired APG signal was then processed in real-time, and carotid RWTT was displayed in a beat-by-beat way. Also, an additional hardware module, referred to as the hydrostatic pressure sensing unit, was designed for automated correction of the hydrostatic pressure gradient in the carotid blood pressure (BP). The in-vivo validation experiments on 16 healthy subjects aged between 22-37 years in sitting position confirm that the RWTT values can be reliably estimated from the high fidelity carotid APG signals. The mean values of measured carotid RWTT were in the range of 0.24 s - 0.33 s (beat-by-beat variation = 6 % - 15 %). These accelerometric derived RWTT values were then compared with reference ultrasound-based carotid arterial stiffness measures, such as relative distension, distensibility coefficient (DC), and pulse wave velocity (PWV). Accelerometric RWTT evaluations showed a significant correlation with relative distension (R = 0.7), DC (R = 0.65), and carotid PWV (R = 0.68) assessments. Therefore, the prototype accelerometric system is a promising method for long-term continuous monitoring of location-specific arterial stiffness.