Dual-Tracer Dual-Bed Hybrid PET/MR Imaging to Study Atherosclerosis Pre and Post Sleep Apnea Treatment

双示踪剂双床混合 PET/MR 成像研究睡眠呼吸暂停治疗前后的动脉粥样硬化

• 批准号: 9438239
• 负责人: neomi A shah
• 金额: $ 8.48万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9438239
• 关键词: Affect; American; Aorta; Arterial Fatty Streak; Atherosclerosis; Beds; Blood Vessels; Breast Microcalcification; Cardiac; Cardiac health; Cardiology; Cardiovascular Diseases; Carotid Arteries; Characteristics; Chest; Clinical Trials; Continuous Positive Airway Pressure; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Deoxyglucose; Diagnosis; Discipline; Discipline of Nuclear Medicine; Discrimination; Event; Future; Hispanic Community Health Study; Hybrids; Hypoxemia; Image; Individual; Inflammation; Injectable; Intervention Studies; Left; Link; Magnetic Resonance Imaging; Measures; Medicine; Molecular; Morphology; Myocardial Infarction; Neck; Participant; Pathway interactions; Patients; Pilot Projects; Positron-Emission Tomography; Process; Protocols documentation; Recording of previous events; Recruitment Activity; Research; Risk; Risk Factors; Rupture; Scanning; Science; Signal Transduction; Sleep; Sleep Apnea Syndromes; Sodium Fluoride; Stroke; Time; Tissues; Tracer; cardiovascular disorder risk; cerebrovascular; clinical care; cohort; design; disorder risk; experience; imaging study; improved; in vivo imaging; innovation; interest; novel; population based; randomized trial; regional difference; treatment response; uptake; vascular bed

Sleep apnea (SA), which affects more than 18 million Americans, is characterized by intermittent hypoxemia and inflammation that may in turn promote atherosclerosis and cardiovascular disease (CVD). SA is associated with an increased stroke risk but its association with myocardial infarction (MI) is less clear. Moreover, results from the largest available randomized trial suggest that SA treatment reduces stroke risk but not incident coronary artery disease (CAD) risk. To explain these findings, the candidate hypothesizes that (1) SA differentially affects carotid vs. coronary atherosclerosis, which may partially explain differences in stroke vs. MI risk; and (2) SA treatment improves carotid but not coronary atherosclerosis. The R03 builds upon the candidate's K-23 project on SA and MI characteristics measured using cardiac magnetic resonance imaging (MRI). In this proposed R03 the candidate will utilize state-of-the-art hybrid Positron Emission Tomography (PET)/MR imaging in SA patients to quantify and compare atherosclerotic plaque inflammation and microcalcification in the carotid and coronary arteries before and after SA treatment (with continuous positive airway pressure [CPAP] for four months). Additionally, the candidate proposes a novel dual-tracer PET/MR approach where they will combine imaging of inflammation (using [18F]-Fluoro-2-deoxy-D-glucose [FDG]) and microcalcification (using [18F]-Sodium Fluoride [NaF]) in atherosclerotic plaques. With this novel protocol the candidate plans to assess the degree to which SA influences distinct atherosclerotic mechanistic processes. Therefore, Aim 1 will quantify and compare intraplaque inflammation in the carotid vs. coronary arteries of SA patients. Aim 2 will quantify and compare the impact of four months of CPAP treatment on intraplaque inflammation in the carotid vs. coronary arteries of patients with SA. Aim 3 will conduct exploratory analysis to quantify and compare intraplaque microcalcification in the carotid vs. coronary arteries in SA patients at baseline and after four months of CPAP treatment. Findings from this research may explain why SA has a stronger stroke vs. CAD effect. It may result in a paradigm shift in SA and cardiovascular disease risk with a stronger emphasis on stroke as an endpoint in clinical trials and in routine clinical care. By identifying a stronger link with carotid than coronary atherosclerosis, it may direct research to identify pathways that drive atherosclerosis processes in the two vascular beds ultimately allowing for tailored therapies for individuals at risk for these disorders, even beyond the SA setting.

睡眠呼吸暂停（SA），影响超过1800万美国人，其特征是间歇性低氧血症 和炎症，反过来可能会促进动脉粥样硬化和心血管疾病（CVD）。SA是 与中风风险增加有关，但与心肌梗死（MI）的关系尚不清楚。 此外，最大的随机试验结果表明，SA治疗可降低中风风险， 无冠心病（CAD）风险。为了解释这些发现，候选人假设（1） SA对颈动脉粥样硬化和冠状动脉粥样硬化的影响不同，这可能部分解释了中风的差异 vs. MI风险;（2）SA治疗改善颈动脉粥样硬化，但不改善冠状动脉粥样硬化。R 03基于 候选人关于使用心脏磁共振成像测量的SA和MI特征的K-23项目 （MRI）。在本申报R 03中，候选人将使用最先进的混合正电子发射断层扫描仪 (PET)/SA患者的MR成像，以量化和比较动脉粥样硬化斑块炎症， SA治疗前后颈动脉和冠状动脉微钙化（持续阳性） 气道压力[CPAP] 4个月）。此外，候选人提出了一种新型的双示踪剂PET/MR 他们将结合炎症联合收割机成像（使用[18 F]-Fluoro-2-deoxy-D-glucose [FDG]）和 微钙化（使用[18F]-氟化钠[NaF]）。有了这个新的协议， 候选人计划评估SA影响不同动脉粥样硬化机制过程的程度。 因此，目标1将量化和比较SA颈动脉与冠状动脉斑块内炎症 患者目标2将量化和比较4个月CPAP治疗对斑块内的影响， SA患者颈动脉与冠状动脉的炎症。Aim 3将进行探索性分析， 量化和比较SA患者颈动脉与冠状动脉斑块内微钙化， 在基线和CPAP治疗四个月后。这项研究的结果可以解释为什么SA具有 中风对CAD的影响更强。它可能导致SA和心血管疾病风险的范式转变， 在临床试验和常规临床护理中更加强调卒中作为终点。通过识别 与颈动脉的联系比冠状动脉粥样硬化更强，它可能指导研究，以确定驱动动脉粥样硬化的途径。 动脉粥样硬化过程中的两个血管床，最终允许个性化治疗的个人， 这些疾病的风险，甚至超出SA设置。