Jayaraj Joseph

An arterial compliance, dual-element photoplethysmograph probe for local pulse wave velocity (PWV) measurement was developed. Initially, the experimental validation study was performed on 25 young volunteers (age =24.5 ± 4 years). Local PWV was assessed from a small section (23 mm) of the carotid artery. The prototype device demonstrated its capability of measuring reliable, repeatable, and reproducible carotid local PWV. Further, in 15 healthy male volunteers (age = 22.25 ± 3.5 years), carotid local PWV and brachial blood pressure (BP) were continuously recorded during their postexercise recovery period. Local PWV followed the changes in arterial BP parameters. The group average correlation coefficients (r) of local PWV versus BP parameters were between 0.772 ± 0.033 and 0.934 ± 0.028. In a population of 50 patients (normotensive and hypertensive) aged 24-80 years, local PWV-BP correlations were investigated. Local PWV tended to follow the diastolic BP (DBP; r = 0.82) and mean arterial pressure (r = 0.83) better than systolic BP (SBP; r = 0.69). It was significantly inferior in tracking pulse pressure values (r = 0.35). Cuffless estimation of arterial pressure was also performed on the same patients using measured carotid local PWV with best-case calibrations. Local PWV yielded good DBP prediction than SBP prediction. Statistically, significant correlation (r = 0.79) and a root-mean-square error of 5.26 mmHg versus reference brachial DBP were achieved. The introduced technique has a potential for short- or long-term noninvasive, cuffless monitoring of BP parameters from superficial arteries.

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.

Local pulse wave velocity (PWV), a metric of the target artery's stiffness, has been emerging in its clinical value and adoption. State-of-the-art ultrasound technologies used to evaluate local PWV based on pulse waves' features are sophisticated, non-real-time, and are not amenable for field and resource-constrained settings. In this work, we present an image-free ultrasound system to measure local PWV in real-time by employing a pair of ultrasound transducer elements. An in vitro study was performed on the arterial phantom to: 1) characterize the design aspects of the system and 2) validate its accuracy against beat-by-beat (invasive) local PWV measured by a reference dual-element catheter. Furthermore, a repeatability and reproducibility study on 33 subjects (21-52 years) investigated the in vivo measurement feasibility from the carotid artery. With the experimentally deduced optimal design (frame-rate =500 Hz, RF sampling rate =125 MHz, LPF cutoff =14 Hz, and order =4 ), the system yielded repeatable beat-to-beat measurements (variability =1.9 % and over 15 cycles) and achieved a high accuracy (root-mean-square-error =0.19 m/s and absolute-percentage-error =2.4 %) over a wide range of PWVs (2.7-11.4 m/s) from the phantom. Subsequently, on human subjects, the intra- and inter-operator PWV measurements were highly repeatable (intraclass correlation coefficient >0.92 ). The system does not impose a demand for special processors with high-computational power while offering real-time feedback on acquisition and measurement quality and provides local PWV online. Future large population and animal studies are required to establish the device's clinical usability.

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.

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.

Purpose: Carotid artery properties can be evaluated with high accuracy and reproducibility using multiple M-line ultrasound. However, the cost of multiple M-line-based imaging modalities and the extensive operator expertise requirements hamper the large-scale application for arterial properties assessment, particularly in resource-constrained settings. This study is aimed to assess the performance of a single M-line approach as an affordable and easy-to-use alternative to multiple M-line imaging for screening purposes. Methods: We used triplicate longitudinal common carotid artery (CCA) ultrasound recordings (17 M-lines covering about 16 mm, at 500 frames per second) of 500 subjects from The Maastricht Study to assess the validity and reproducibility of a single against multiple M-line approach. The multiple M-line measures were obtained by averaging over all available 17 lines, whereas the middle M-line was used as a proxy for the single M-line approach. Results: Diameter, intima-media thickness (IMT), and Young's elastic modulus (YEM) were not significantly different between the single and multiple M-line approaches (p > 0.07). Distension and distensibility coefficient (DC) did differ significantly (p < 0.001), however, differences were technically irrelevant. Similarly, Bland-Altman analysis revealed good agreement between the two approaches. The single M-line approach, compared to multiple M-line, exhibited an acceptable reproducibility coefficient of variation (CV) for diameter (2.5 vs. 2.2%), IMT (11.9 vs. 7.9%), distension (10 vs. 9.4%), DC (10.9 vs. 10.2%), and YEM (26.5 vs. 20.5%). Furthermore, in our study population, both methods showed a similar capability to detect age-related differences in arterial stiffness. Conclusion: Single M-line ultrasound appears to be a promising tool to estimate anatomical and functional CCA properties with very acceptable validity and reproducibility. Based on our results, we might infer that image-free, single M-line tools could be suited for screening and for performing population studies in low-resource settings worldwide. Whether the comparison between single and multiple M-line devices will yield similar findings requires further study.

Over past few years our group has been working on the development of a low-cost device, ARTSENS, for measurement of local arterial stiffness (AS) of the common carotid artery (CCA). This uses a single element ultrasound transducer to obtain A-mode frames from the CCA. It is designed to be fully automatic in its operation such that, a general medical practitioner can use the device without any prior knowledge of ultrasound modality. Placement of the probe over CCA and identification of echo positions corresponding to its two walls are critical steps in the process of measurement of AS. We had reported an algorithm to locate the CCA walls based on their characteristic motion. Unfortunately, in supine position, the internal jugular vein (IJV) expands in the carotid triangle and pulsates in a manner that confounds the existing algorithm and leads to wrong measurements of the AS. Jugular venous pulse (JVP), on its own right, is a very important physiological signal for diagnosis of morbidities of the right side of the heart and there is a lack of noninvasive methods for its accurate estimation. We integrated an ECG device to the existing hardware of ARTSENS and developed a method based on physiology of the vessels, which now enable us to segregate the CCA pulse (CCP) and the JVP. False identification rate is less than 4%. To retain the capabilities of ARTSENS to operate without ECG, we designed another method where the classification can be achieved without an ECG, albeit errors are a bit higher. These improvements enable ARTSENS to perform automatic measurement of AS even in the supine position and make it a unique and handy tool to perform JVP analysis.

Over past few years our group has been developing a fully automated and low-cost device, ARTSENS (ARTerial Stiffness Evaluation for Non-invasive Screening), to enable non-experts to measure arterial stiffness (AS). It uses a single element ultrasound transducer to obtain A-mode frames from a superficial artery such as the common carotid artery (CCA) and analyzes them to obtain the stiffness parameters of the vessel.Wehave earlier demonstrated that ARTSENS can accurately measure local arterial stiffness (LAS) and regional arterial stiffness (RAS) by tracing the distension waveforms of the CCAand the femoral artery. In this paper, we show that it is possible to estimate the augmentation index (AIx), a measure of the global arterial mechanics, from the distension waveforms obtained by ARTSENS. AIx measurements from ARTSENS are compared against the state-of-the-art Hitachi- Aloka eTRACKING system for 107 volunteers. Both devices show excellent agreement with a correlation coefficient (r)=0.82 (p<0.0001), which is comparable to similar studies reported in the literature. This development makes ARTSENS a unique device that can measure the three most widely used indices of arterial mechanics-LAS, RAS and the AIx.

Arterial stiffness (AS) of the carotid artery is an early marker of stratifying cardiovascular disease risk. This article aims to improve the performance of ARTSENS, a noninvasive A-mode ultrasound-based device for measuring AS. The primary objective of ARTSENS is to enable the measurement of elastic modulus using A-Mode ultrasound and blood pressure. As this device is image-free, there is a need to automate: 1) carotid detection; 2) wall localization; and 3) inner lumen diameter measurement. This has been performed using conventional signal processing methods in some of the earlier works in this domain. In this article, deep neural network (DNN) models are employed to perform the above three tasks. The DNNs were trained over data acquired from 82 subjects at two different medical centers. Ground-truth labeling was performed by a trained operator using corresponding measurements from the state-of-the-art Aloka e-Tracking system. All three DNN models had significantly lower errors compared to earlier signal processing methods and could perform their measurements using a single A-Mode frame. Using the DNNs, two different machine learning pipelines have been proposed here to measure the elastic modulus; the best among them could achieve an error of 9.3% with the Pearson correlation coefficient of 0.94 ( p < 0.001 ). The models were tested on Raspberry Pi and Jetson Nano single board computers to demonstrate real-time processing on low computational resources.

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.