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.

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.

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.

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.

The velocity of propagation of arterial blood pulse signals obtained from a smaller arterial section referred as local pulse wave velocity (PWV) is an index of cardiovascular events of a particular artery. In this work, we introduce a novel design of accelerometer probe for local PWV measurement from the carotid artery. The proposed probe was developed using highly sensitive dual MEMS accelerometers. The probe design with tiny dual element sensors was capable of simultaneously acquiring acceleration signals generated due to arterial wall displacement towards the skin surface. Measurements were performed from carotid artery over a smaller arterial section of length 24 mm. The ability of the probe to acquire continuous arterial waveforms and cycle-to-cycle local PWV measurement was verified by conducting an in-vivo test in multiple subjects (11 volunteers aged between 20 - 60 years) under controlled settings. Reliable as well as repeatable signals (maximum beat-to-beat variation was less than 13%) and carotid PWV measurement with high reproducibility was obtained. A correlation examination of the local PWV with heartrate and BP was conducted during the same study. A statistically significant correlation was observed with the correlation coefficient greater than 0.78 for BP parameters and 0.66 for heartrate. In-vivo validation study promising the potential use of the developed accelerometer probe for cuffless evaluation of BP parameters and heartrate as a confounder of local PWV assessment was obtained.

Continuous monitoring of blood oxygen saturation level (SpO2) is crucial for patients with cardiac and pulmonary disorders and those undergoing surgeries. SpO2 monitoring is widely used in a clinical setting to evaluate the effectiveness of lung medication and ventilator support. Owing to its high levels of accuracy and stability, transmittance pulse oximeters are widely used in the clinical community to compute SpO2. Transmittance pulse oximeters are limited to measure SpO2 only from peripheral sites. Reflectance pulse oximeters, however, can be used at various measurement sites like finger, wrist, chest, forehead, and are immune to faulty measurements due to vasoconstriction and perfusion changes. Reflectance pulse oximeters are not widely adopted in clinical environments due to faulty measurements and inaccurate R-value based calibration methods. In this paper, we present the analysis and observations made using a machine learning model for SpO2 computation using reflectance Photoplethysmogram (PPG) signals acquired from the finger using the custom data acquisition platform. The proposed model overcomes the limitations imposed by the traditional R-value based calibration method through the use of a machine learning model using various time and frequency domain features. The model was trained and tested using the clinical data collected from 95 subjects with SpO2 levels varying from 81-100% using the custom SpO2 data acquisition platform along with reference measures. The proposed model has an absolute mean error of 0.5% with an accuracy of 96 ± 2% error band for SpO2 values ranging from 81-100%.

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.