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

摘要 拟议的培训补助金旨在通过以下方式促进医学博士维什纳维·昆德尔的学术生涯 以她在临床睡眠医学方面的深厚背景为基础，从事以患者为中心的研究，以及 在探索睡眠在心脏代谢性疾病风险中的作用方面发展专业知识。通过这项提议，她将 接受多学科培训，以调查慢性睡眠剥夺和睡眠不规律的可能性 用多模式成像-混合法测量动脉粥样硬化和内脏肥胖的可改变的危险因素 18F脱氧葡萄糖(FDG)PET/MRI。研究计划：这项拟议的研究建立在昆德尔博士的试验基础上 由AASM资助的研究。其目的是确定习惯性的短睡眠时间和睡眠 不规则性与血管炎症和内脏肥胖症(两者之间有很强的联系)有关 增加心血管疾病风险)，独立于阻塞性睡眠呼吸暂停综合征(通常是这些关联中的混杂因素)。我们将利用多天制 肌动记录仪收集客观的睡眠指标，PET/MRI测量血管炎症和内脏 在招募的患者中，脂肪组织(VAT)代谢活性(脂肪组织炎症的新标记物)。 随着拟议的培训和研究的成功完成，我们希望强调慢性病的作用 睡眠剥夺和睡眠不规律在心脏代谢风险中的作用，建立一个成像生物标记物的指数 未来的研究。此外，结果将为未来(R01)提案提供方向-奠定基础 为了发展多学科合作来阐明睡眠调节炎症的机制， 长期目标是在这部分患者中确定早期心血管风险的生物标记物，以及 设计睡眠延长研究。职业发展：昆德尔博士的培训计划具有出色的 西奈山伊坎医学院的研究环境和全国知名的导师 和具有免费专业知识的顾问。她的主要指导团队包括：(A)医学博士Neomi Shah， 公共卫生硕士，硕士(阻塞性睡眠呼吸暂停[OSA]和心血管(CV)疾病专家)，以及 OSA的先进心血管成像)(B)Indu Ayappa博士，博士(获得K-24指导奖， 睡眠呼吸暂停、睡眠生理学和活动描记用于客观睡眠评估的专门知识)(C)Zahi Fayad博士 和菲利普·罗布森博士(利用多模式成像评估动脉粥样硬化和器官的专家 系统生物学)。她的培训以精心设计的课程和实践经验相结合为特色。 在1)用于客观睡眠指标综合评估的活动图2)多模式心脏代谢 影像3)临床研究设计和以患者为中心的研究4)未来生物标记物科学的培训 提案。她的导师和顾问一起在指导初级教员方面取得了成功的记录 职业发展奖，广泛的合作和赠款组合，为以下项目提供坚实的基础 昆德尔博士目前的提议，并最终成功地发展成为一名独立的调查人员。

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.