Jayaraj Joseph

As frequent monitoring of vascular ageing is gaining importance and the lack of a wearable sensing technology to track it through changes in vascular stiffness, we have developed a wearable accelerometric device. It could capture changes in vascular stiffness using our empirically derived markers from the amplitude features of acceleration plethysmogram (APG) at the carotid artery site. An in-vivo study on 12 subjects was conducted to (a) identify a few amplitude-based markers from the APG that exhibit significant change to physiologically induced hemodynamic perturbation; and (b) compare the magnitude of response of these APG-derived markers with that of carotid local stiffness metrics (β, Ep, and AC) measured using a clinically validated device, ARTSENS® Pen. The APG signals were reliable (SNR > 38 dB) and the amplitude features of APG were repeatable (CoV < 10 %). By examining all the APG-derived markers that showed statistically significant differences (p < 0.05) between pre and post-exercise measurements, it was found that the markers (ab)*(a-c) and (a*b) were having a high magnitude of response among others. The response (expressed as a percentage difference in mean values between pre and post-measurements) of the APG-derived markers, (a-b)*(a-c) and (a*b) were 42.41 % and 40.55 %, respectively, which were comparable to the response of carotid local stiffness metrics, β (32.34 %) and AC (41.83 %). The results suggest the potential of APG-derived markers, (a*b) and (a-b)*(a-c) for tracking stiffness changes, and the pilot study demonstrated the ability of the device to capture stiffness changes for ambulatory monitoring purposes.

In this work, we present a novel approach for ubiquitous blood pressure (BP) measurement that involves a deep learning technique based on the extraction of the inherent features that are indicative of arterial pressure-diameter and pulse transit relationships. The proposed artificial neural network (ANN) architecture is the first to use the combined features of local arterial dimensions and blood pulse propagation characteristics for continuous, cuffless BP estimation. A dual-channel A-mode ultrasound system and a probe with a pair of single-element ultrasound transducers were developed for simultaneous measurement of luminal diameter waveforms from small arterial segments. In our present system, the probe design was optimized to capture local vessel dynamics from the common carotid artery. The reference continuous BP corresponding to individual cardiac cycles was acquired from the same arterial segment using a tonometer synchronized with the diameter measurement system. The data required to train and validate the developed ANN-based BP estimation model was recorded by conducting an in-vivo study on 20 young subjects. Thirty-seven unique features derived from the dual diameter waveform were extracted for beat-by-beat measurement of BP parameters from the carotid site, and hence to construct the carotid pressure waveform. Experimental results showed that the proposed approach exhibited an acceptable accuracy, with a root-mean-square-error of 4 mmHg and 6 mmHg for DBP and SBP respectively. In conclusion, the proposed approach provides a potentially novel cuffless BP technique for continuous measurement of arterial pressure waveform.

Vascular stiffness is an indicator of cardiovascular health, with carotid artery stiffness having established correlation to coronary heart disease and utility in cardiovascular diagnosis and screening. State of art equipment for stiffness evaluation are expensive, require expertise to operate and not amenable for field deployment. In this context, we developed ARTerial Stiffness Evaluation for Noninvasive Screening (ARTSENS), a device for image free, noninvasive, automated evaluation of vascular stiffness amenable for field use. ARTSENS has a frugal hardware design, utilizing a single ultrasound transducer to interrogate the carotid artery, integrated with robust algorithms that extract arterial dimensions and compute clinically accepted measures of arterial stiffness. The ability of ARTSENS to measure vascular stiffness in vivo was validated by performing measurements on 125 subjects. The accuracy of results was verified with the state-of-the-art ultrasound imaging-based echo-tracking system. The relation between arterial stiffness measurements performed in sitting posture for ARTSENS measurement and sitting/supine postures for imaging system was also investigated to examine feasibility of performing ARTSENS measurements in the sitting posture for field deployment. This paper verified the feasibility of the novel ARTSENS device in performing accurate in vivo measurements of arterial stiffness. As a portable device that performs automated measurement of carotid artery stiffness with minimal operator input, ARTSENS has strong potential for use in large-scale screening.

Various arterial segments in the macrovasculature exhibit heterogeneity in terms of the structural and functional properties. Owing to the difference in the structural composition, there exists a stiffness gradient from central to peripheral arteries. The loss in this gradient is multifactorial, such as aging, plaque formation, degradation of vessel elastin etcetera. This is a proven pathophysiological basis for cardiovascular risks, chronic kidney diseases, and end-organ damage. Clinical studies have reported the importance of measuring the local stiffness from peripheral arteries along with the central arteries. However, there is an unmet need for easy-to-use, portable, and non-expert operable tool for performing the stiffness measurements from individual target arteries. In this work, we have demonstrated the feasibility of using a highly compact image-free ultrasound device, ARTSENS® Pen, for measuring the central (carotid) and peripheral (brachial) arterial stiffness together. An in-vivo study was performed on a cohort of 19 subjects within the age group of 20 - 55 years for the same. The diameter and stiffness measurements performed in the recruited subjects were repeatable for both the arteries with a beat-to-beat coefficient of variation smaller than 5.3% and 7.5% respectively. The group average stiffness index for the brachial artery was observed to be higher than that of the carotid artery. The slope of the relationship between the carotid β stiffness versus the age of the subjects was higher compared to brachial, indicating higher stiffness progression rate for the carotid artery. A gradient reversal for the recruited population was observed for the older population. These observations were consistent with the theory and the earlier reported studies. In conclusion, the proposed technology provides a potential easy-to-use compact tool for performing fully automated stiffness measurements from multiple heterogeneous arterial sites.

Evaluation of arterial compliance is very significant in early detection of coronary heart disease. Here we present an imageless portable system for automated estimation of local arterial compliance, designed to be operated by a general medical practitioner with no prior knowledge of ultrasonography. An algorithm for automatic detection and tracking of the arterial wall locations has been developed to minimize the operator expertise required for measurement. The performance of the automated algorithm was thoroughly characterized using a simulation platform developed for the purpose. Measurements performed on a few human volunteers by untrained personnel clearly illustrated the practical utility of the automatic algorithm during in-vivo tests. The proposed system could be used for developing an inexpensive cardiovascular screening device for large scale deployment in primary health care centers. © 2012 IEEE.

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.

Evaluation of vascular stiffness is significant in diagnosis for early detection of vascular injury and has potential in screening individuals at risk of future cardiovascular events. State of art techniques use an imaging system for measuring carotid artery stiffness, or rely on carotid-femoral pulse wave velocity (PWV) to evaluate vascular stiffness. These techniques are costly, require expertise to perform and are not amenable for scaling to the population level. To address this gap, we have developed ARTSENS® Pen, a high portable, small, ultrasound based instrument for automated evaluation of carotid artery stiffness. The device has an integrated hardware for ultrasound signal acquisition and digitization that operate along with any Windows tablet for data visualization and result display. Algorithms for real time signal processing and automated artery wall identification and tracking ensures a completely automated measurement of carotid artery stiffness with no operator input. The accuracy of automated arterial dimension measurements performed by ARTSENS®Pen is verified by phantom studies in comparison with a reference ultrasound imaging system. The ability of the device to provide reliable measures of arterial stiffness in-vivo is verified by a systematic study on 29 volunteers. The inter operator and intra-operator variability of stiffness index, β was evaluated to be 17% and 9% respectively. The ARTSENS® Pen was found to be capable of providing accurate and repeatable measures of arterial stiffness in an easy manner and has strong potential in large scale vascular screening.

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.

The measure of arterial stiffness is significant for the diagnosis of the cardiovascular health. A prototype accelerometer- based system for vascular stiffness indices detection is proposed and experimentally validated. The developed accelerometer-based system could continuously capture the accelerations related to the displacement of the carotid arterial walls. The measured accelerometric waveforms are recorded by a data acquisition card for signal processing and analysis in real-time. The recorded accelerometric signals from the carotid skin surface are double- integrated and calibrated linearly using our clinically validated ARTSENS® (ARTerial Stiffness Evaluation for Noninvasive Screening) device to estimate the subject-specific one-time calibration coefficients. The acquired accelerometric signal with these calibration coefficients was used to estimate the diameter parameters such as arterial distension (Δ D), end-diastolic diameter (Dd), and systolic diameter (D s). 12 subjects (7 males, 5 females, age =25.42± 2.5 years) with no prior history of cardiovascular diseases were enrolled for the in-vivo validation study. The accelerometer-based system could capture continuous distension waveforms for all the recruited subjects. Arterial stiffness indices such as stiffness index (β), arterial compliance (AC) and Peterson's elastic modulus (Ep) were calculated using the obtained diameter parameters from the accelerometer-based system. The correlation (R2) for β, AC and Ep observed between ARTSENS reference device and accelerometric system were 0.93, 0.95 and 0.94 respectively. Bland-Altman plots of β, AC, and Ep of ARTSENS reference device and the accelerometric system shows a small mean bias of 0.07, -0.001 and 0.81 respectively. The preliminary results suggest the potential of the accelerometer- based system for vascular wall stiffness indices detection.

There is an ever-increasing interest in the research community towards the development of advanced in-vivo diagnostic and screening tools for cardiovascular diseases. Various methodologies often do not account for potential errors in arterial pressure and diameter measurements. This paper highlights these pitfalls through the design and instrumentation of a bi-modal probe integrated with A-scan ultrasound and force sensor. This probe is used for simultaneous and single-site assessment of pressure - diameter (PD) loop of superficial arteries. In-vivo measurement of PD loop is a gateway to study the mechanical properties of artery, design and development of vascular grafts and clinically significant for measurement of arterial stiffness, local pulse wave velocity, and central blood pressure. The novelty comes with the usage of an image free A-scan mode of ultrasound, which makes it possible to keep the force sensor and ultrasound transducers very close, solving one of the challenges faced by state-of-the-art techniques in single site measurement. In addition to this, in-house-developed acquisition hardware and software ensures matched frequency response and time synchronization for both pressure and diameter signals. Signals were reliably recorded with an SNR of 20 dB and constructed PD loop is in the clockwise direction with pressure signals leading diameter signals.