Assessment of Endothelial Reactivity by Measurement of Vascular Material Response to Shear Stress: A Feasibility Study.

Flow-mediated dilation (FMD) evaluates the relative change in arterial diameter during hyperemia to assess the endothelial response due to a shear stimulus. However, conventional FMD measures diameter response alone and the alterations in the arterial wall's material properties during reactive hyperemia, which also influence dilation, go unaddressed. In this work, we examine the material response (MR) of the artery during reactive hyperemia using clinically relevant stiffness markers for the assessment of endothelial reactivity (ER). For this, we have developed an in-house brachial cuff control (BCC) system to continuously acquire brachial pressure which can be integrated with simultaneous measurement of brachial diameter and used to quantify the relative changes in wall property during hyperemia non-invasively. The assessment of endothelial reactivity using material response (ERAMR) was conducted on 20 healthy participants (12M/8F) and the results were compared with conventional FMD (FMD%). The mean pressure response gave an inverse trend to that of diameter response with varying magnitudes during reactive hyperemia (18.71% from baseline for diameter and 2.45% for pressure), there was a significant difference in the measurement of FMD and ERAMR (P < 0.05). The larger distribution of ERAMR compared to FMD% in box-plots further implies the inclusion of within-subject variations. Hence, ERAMR can be a potential estimate of ER, given the need for intensive validations in this line on larger cohorts.Clinical Relevance- This study demonstrates the independent role of arterial wall material properties to quantify endothelial reactivity in response to a shear stimulus.

Normalization of Flow-mediated Dilation to Brachial Artery Material Property: A Feasibility Study.

Endothelial reactivity (ER) is widely measured using flow-mediated dilation (FMD) of brachial artery. Conventional measurement of FMD is influenced by factors such as input shear stress, arterial transmural pressure, diameter and thereby arterial material properties (ε). Thus, for a reliable interpretation of FMD, it has to be normalized with respect to the above confounding factors. Normalization of FMD with shear stress at the time of measurement has been reported to reduce measurement variability. However, its widespread usage among the research community is limited. In this work, we examine the feasibility of normalizing the brachial FMD index (FMD%) to ε : extrema (εp), baseline (εb) and extrema change (∆ε) post-ischemia using its inter-day variability against FMD. In-vivo measurements were performed on 10 participants for 2 consecutive days and simultaneous pressure-diameter cycles were collected to estimate the material properties during reactive hyperemia (RH). The box-whisker plot reveals differences in the mean and deviation of FMD to FMD|εb. A significant value for repeatability (ICC ≥ 0.6) was obtained for normalized FMD (FMD|εb) for specific stiffness index (ß), pressure-strain elastic modulus (Ep), and local pulse wave velocity (PWV) as compared to FMD. Hence, normalization of FMD% to arterial ε can potentially improve the measurement reliability of ER assessment.Clinical Relevance- This pilot study demonstrates the feasibility of brachial artery stiffness assessment during FMD and its potential use for normalizing the standard FMD measurement.

Association of Local Arterial Stiffness and Windkessel Model Parameters with Ageing in Normotensives and Hypertensives.

Computation of arterial stiffness is a well-established, widely accepted method for estimating vascular age. Although carotid-femoral pulse wave velocity is typically used for vascular age assessment, most recent studies have reported the need to consider a combination of local and regional stiffness indices possessing distinct association with the vascular structure and/or function for better prediction of early vascular ageing syndrome. In this work, we investigate the association of clinically validated local stiffness (obtained using biomechanical relations), global stiffness (obtained from 3-element Windkessel modelling), and pulse contour indices from the aorta with ageing and their distribution in normotensives and hypertensives. The analysis was performed on 420 (virtual) subjects (age: 65 ± 11 years) with an equal proportion of hypertensive (age: 65 ± 11 years) and normotensive (age: 65 ± 11 years) subjects. Multivariate linear regression analysis revealed an independent association of each of the indices with age (Adjusted r = 0.75 p < 0.01). Specific stiffness index (r = 0.67, p < 0.001), Augmentation index (r = 0.55, p< 0.001) and total arterial compliance (r = -0.50, p < 0.001) depicted highest correlation with age. There was a significant difference (> 16%, p < 0.001) in mean values of the measured indices between hypertensive and normotensive subjects. The study findings further emphasize the need to combine multiple non-invasive vascular markers to capture the unique aspects of age-induced arterial wall remodelling for reliable monitoring and management of the early vascular ageing syndrome. Clinical Relevance- This study demonstrates an independent and combined predictive role of local/global stiffness and pulse contour indices in ageing.

Breast tumor parameter estimation and interactive 3D thermal tomography using discrete thermal sensor data.

This work uses a simple low-cost wearable device embedded with discrete thermal sensors to map the breast skin surface temperature. A methodology has been developed to estimate diameter, blood perfusion, metabolic heat generation and location in X, Y, Z coordinate of tumor from this discrete set of data. An interactive 3D thermal tomography was developed which provides a detailed 3D thermal view of the breast anatomy. Using this system, the user can interactively rotate and slice the 3D thermal image of the breast for a detailed study of the tumor. Finite element method (FEM) and an evolution-based inverse method were used for the parameter estimation. The method was first validated using phantom experiments and the results obtained were within an error of 10% (0.005 W cm-3) for heat generation and 15% (0.3 cm) for heater location. Further validation was carried out through clinical trials on 60 human subjects. Estimated blood perfusion rate and metabolic heat generation rate exhibit distinguishable difference between cancerous and non-cancerous breast. Estimated diameter and location of tumor in cancerous breast shows good agreement with the actual clinical reports. We have obtained a sensitivity of 82.78% and specificity of 87.09%. Proposed breast tumor parameter estimation methodology with interactive 3D thermal tomography is a good screening tool for breast cancer detection and also useful for clinicians to find out location including depth.