Pericoronary Adipose Tissue, Inflammation, and Subclinical Coronary Artery Disease in People with HIV in Uganda

PROJECT SUMMARY/ABSTRACT Background: People with HIV (PWH) are at increased risk of developing coronary artery disease (CAD) as compared to people without HIV (PWOH). The pathophysiology of CAD amongst PWH is believed to be due to an accelerated inflammatory process, resulting in formation of non-calcified, vulnerable plaques that are often

not detected by standardized diagnostic methods. Pericoronary adipose tissue (PCAT) may serve as a feasible alternative imaging technique for early detection of coronary inflammation among PWH in Uganda, but has not been evaluated in the region. Candidate: The goal of the proposed K43 Emerging Global Leader (K43) Award

is to support Dr. Prossy BIbangambah, a clinician scientist and faculty radiologist at Mbarara University of Science and Technology, to become an independent clinician-scientist with expertise in development and evaluation of innovative imaging techniques to elucidate the mechanisms of HIV-related cardiovascular

disease (CVD) in sub-Saharan Africa. To achieve this, she will gain additional training in: 1) collection and analysis of cardiovascular image modalities for use in clinical research, 2) radiomics methods, including feature selection and machine learning to apply state-of-the-art technology to detect clinical abnormalities, and 3)

statistical methods for diagnostic evaluation and risk prediction. This K43 project will help her achieve her long- term career goals through provision of didactic training in these key areas, mentorship from a team of world experts and practical research experience through the completion of her scientific aims. Research: Dr.

Bibangambah will determine the relationship between PCAT, inflammation, and subclinical CAD in PWH by leveraging data and coronary computed tomography angiography (CCTA) images from two completed NIH- funded study cohorts through completion of the following aims: Aim 1: performing CCTA-based segmentation

of PCAT and comparing the density between PWH and PWOH; Aim 2: using segmented images from Aim 1 to extract PCAT radiomics features and compare the difference in PCAT radiomics signatures between PWH and PWOH; and Aim 3: determining whether PCAT densities from Aim 1 or the radiomics signatures from Aim 2

improve the performance of cardiovascular risk prediction. Innovation: This study will be among the first to evaluate a novel tissue biomarker (PCAT) using CCTA-images and its relationship with inflammation and CAD in PWH in sub-Saharan Africa. Deliverables and future directions: With mentored training and skills gained

from these scientific aims, Dr. Bibangambah will publish six manuscripts and be well-positioned to submit an NIH R01 proposal to evaluate the novel radiomics models/signature in predicting major adverse cardiovascular events (MACE) among people with and without HIV in Uganda.