Use of Novel Multi-modality Imaging to Evaluate the Relationship Between Sleep Duration, Vascular Inflammation, and Visceral Adiposity

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ABSTRACT The proposed training grant is designed to advance the academic career of Dr. Vaishnavi Kundel, MD, by building upon her strong background in clinical sleep medicine to engage in patient-oriented research, and develop expertise in exploring the role of sleep in cardiometabolic disease risk. Through this proposal, she will obtain multidisciplinary training to investigate chronic sleep deprivation and sleep irregularity as potentially modifiable risk factors for atherosclerosis and visceral adiposity measured using multi-modality imaging - hybrid 18fluorodeoxyglucose (FDG) PET/MRI. Research plan: The proposed research builds on Dr. Kundel's pilot studies funded by the AASM. The aims are to determine whether habitual short sleep duration and sleep irregularity are associated with increased vascular inflammation and visceral adiposity (which is strongly linked to increased CVD risk), independent of OSA (often a confounder in these associations). We will utilize multi-day actigraphy to collect objective sleep metrics, and PET/MRI to measure vascular inflammation and visceral adipose tissue (VAT) metabolic activity (a novel marker of adipose tissue inflammation) in the recruited patients. With successful completion of the proposed training and research, we hope to underscore the role of chronic sleep deprivation and sleep irregularity in cardiometabolic risk, establishing an index of imaging biomarkers for future research. Moreover, the results will provide direction for future (R01) proposals - laying the groundwork for developing multidisciplinary collaborations to elucidate mechanisms by which sleep modulates inflammation, with a long-term goal of identifying biomarkers of early cardiovascular risk in this subset of patients, and designing sleep extension studies. Career Development: Dr. Kundel's training plan features an outstanding research environment at the Icahn School of Medicine at Mount Sinai along with nationally renowned mentors and advisors with complimentary expertise. Her primary mentoring team comprises of (a) Dr. Neomi Shah, MD, MPH, MS (expert in obstructive sleep apnea [OSA] and cardiovascular (CV) diseases, and application of advanced cardiovascular imaging in OSA) (b) Dr. Indu Ayappa, PhD, (recipient of a mentored K-24 award, with expertise in OSA, sleep physiology, and use of actigraphy for objective sleep assessments) (c) Drs. Zahi Fayad and Philip Robson, PhD (experts in use of multimodality imaging for assessment of atherosclerosis and organ system biology). Her training features a combination of carefully designed coursework and practical experiences in 1) actigraphy for comprehensive assessments of objective sleep metrics 2) multi-modality cardiometabolic imaging 3) clinical study design and patient-oriented research 4) training in biomarker science for future proposals. Together, her mentors and advisors have a successful track record of mentoring junior faculty in career development awards, with extensive collaborations and grant portfolios to provide a solid foundation for Dr. Kundel's present proposal, and ultimate success in developing into an independent investigator.