Jayaraj Joseph

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

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.

Whole slide imaging (WSI) creates high-resolution digital images of entire tissue samples, enabling accurate and reliable analysis. Consistency in staining is essential for producing high-quality WSI slides. An automated slide stainer is critical in ensuring precise and uniform staining, especially for larger tissue sections where manual staining can be challenging. However, no large format stainers are currently available on the market. A custom-designed automated slide stainer for large tissue sections was developed to address these issues, having the capability to handle various glass slides from the standard 1' × 3' glass slides to the customized 2' × 3', 5' × 7' and 6' × 8' glass slides. The performance of the custom-designed large format automated slide stainer was compared to the Sakura Tissue-Tek Prisma machine and the manual staining method. The image quality of the whole slide images was evaluated using parameters like the signal-to-noise ratio and the consistency of the image histograms. The automated stainer showed a low intra-slide variation of stain intensity, with a lower standard deviation (SD) of 13.005 ± 1.515 compared to the manual method's SD of 17.315 ± 3.31. In addition, the automated slide staining showed a lower SD (Nissl = 1.795, Hematoxylin and Eosin (H&E) = 2.56) in Signal-to-Noise Ratio (SNR) values compared to manual staining (Nissl = 6.282, H&E = 5.31), indicating excellent staining uniformity. Overall, the automated slide stainer had consistent staining across slides, with a low pairwise distance of 0.0070 ± 0.0017 (Nissl) and 0.0060 ± 0.0003 (H&E). Based on the image evaluation, the custom-designed large-format automated slide stainer was shown to be a reliable, repeatable, and consistent method for staining large tissue samples of sizes up to 150 × 200 mm.

Breast cancer is the second largest cause of cancer death among women after skin cancer. Mitotic count is an important biomarker for predicting the breast cancer prognosis according to Nottingham Grading System. Pathologists look for tumour areas and select 10 HPF(high power field) images and assign a grade based on the number of mitotic counts. Mitosis detection is a tedious task because the pathologist has to inspect a larger area. The pathologist's views about mitotic cell are also subjective. Because of these problems, an assisting tool for the pathologist will generalize and reduce the time for diagnosis. Due to recent advancements in whole slide imaging, CAD(computer-aided diagnosis) systems are becoming popular. Mitosis detection for scanner images is difficult because of variability in shape, color, texture and its similar appearance to apoptotic nuclei, darkly stained nuclei structures. In this paper, the mitotic detection task is carried out with state of the art object detector (Faster R-CNN) and classifiers (Resnet152, Densenet169, and Densenet201) for ICPR 2012 dataset. The Faster R-CNN is used in two ways. In first, it was treated as an object detector which gave an F1-score of 0.79 while in second, it was treated as a Region Proposal Network followed by an ensemble of classifiers giving an F1-score 0.75.

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.

Arterial Young's modulus (Y) is an important elastic property of the artery that quantifies the material stiffness. Several studies have demonstrated that the quantitative values of Y and its standard deviation could be potentially used as an independent predictor of coronary heart diseases. For reliable measurements of Y, accurate measurements of arterial diameter and wall thickness are required. Conventionally these arterial dimensions are measured by imaging systems that are not a viable option for large-scale screening due to their form factor and a high degree of complexity. In this work, we present a portable image-free ultrasound modality - ARTSENS Pen for measurement of Y. ARTSENS is an extensively validated technology that is capable of providing clinical standard measurements of arterial dimensions and stiffness. In this present work, we have demonstrated the capability of the ARTSENS to make accurate and repeatable measurements of Y. The performance of the device is validated through an in-vivo study on 15 subjects. The ARTSENS measurements of Y were repeatable over continuous cardiac cycles for all the recruited subjects (beat-to-beat variation < 6 %). The mean of Y measured for all the subjects was 262.8±99 kPa. The accuracy of the system was evaluated by a comparative analysis against a reference B-mode imaging modality. Regression analysis of the data showed that the Y measurements that were taken by ARTSENS significantly correlated (r = 0.90, p < 0.001) to the reference system measurements. Bland Altman analysis indicated a strong degree of agreement between measurements taken by the two devices, with an insignificant difference (p = 0.32).

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.

We study the potential of reflectance photoplethysmography (PPG) in monitoring free flaps for arterial and venous thrombosis in post-surgical scenarios. Circulatory disruptions due to thrombosis were simulated using limb ischemia method on 30 volunteers. Arterial and venous occlusions were conducted in this study. The variation in blood flow in the region of interest was captured by a custom built sensor and data acquisition system using dual wavelength reflectance photoplethysmography. The main chromophores in blood, oxygenated and reduced hemoglobin, showed good variation to visible - near infrared wavelengths with concentration and volume changes. Sensitivity of the prototype device in detecting arterial and venous circulation disruptions was evaluated at various different threshold levels of signal parameters. The device showed strong capability to accurately detect circulatory disruptions and has potential in post-surgical monitoring of free flaps.

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.