The Effect of Mindfulness on Vascular Inflammation in Stable Coronary Disease: A Multi-System PET/MRI Study

摘要： 慢性心理社会应激暴露是心血管疾病的一个有效但在很大程度上未被认识到的危险因素。 疾病（CVD）;然而，潜在的机制仍然不确定。慢性压力触发神经激素- 最终的反应，但上游的大脑中心启动这级联不完全定义。最近的几 研究表明，更高的压力与炎症增加有关，炎症增加会导致CVD。此外，委员会认为， 越来越多的研究表明，通过修改 大脑活动和减少全身炎症和CVD症状。正电子先进成像 发射断层扫描和磁共振成像（PET/MRI）提供了一个机会， 评估与压力相关的神经中心的神经生物学活性（例如，杏仁核）参与 启动这一途径，同时评估其他几个组织的活动，可能partic- ipate在这一机制，如骨髓和动脉壁，以获得新的机制的见解。 在这种模式下，我们的研究小组已经表明，杏仁核的高度活动与增加的 骨髓活性和动脉壁炎症增加。目前的建议涉及这些问题 通过评估正念减压对动脉炎症的影响来了解知识差距（目的 1)以及杏仁核活性和全身性炎症（Aim 2）， 使用PET/MRI诊断疾病。这项随机对照试验将招募36名受试者， 或接受常规治疗，接受基线和随访成像和炎症生物标志物检查。受试者 混杂条件（即，精神或神经疾病等）将被排除在外。迈克尔·奥斯本博士是 哈佛医学院和马萨诸塞州总医院（MGH）的医学讲师，高度 有资格并投资领导这项研究。他在工程和先进成像方面有着独特的背景 以及成功研究的跟踪记录，包括出版物和奖项，使用几种成像方式。 通过这项提议，他将发展多系统PET/MRI方面的专业知识，并提高他在多系统PET/MRI方面的基础。 临床试验，生物统计学，炎症生物学，压力和身心医学的心理学，同时产生 过渡到R级独立NIH支持的研究所需的数据和概况。他的长期目标是 应用多参数PET/MRI更好地了解压力和身体疾病之间的关系 找出有效的治疗方法。他得到了由艾哈迈德博士领导的合格导师团队的支持 Tawakol是一位心脏病专家，在PET方面有专长，他还包括其他NIH资助的放射学、心理学和医学研究人员。 流行病学和心脏病学。他的机构环境稳健，并且有着悠久的支持历史 通过各种资源，包括教学法，设施和指导，早期调查员的发展。的 MGH心脏病科向Osborne博士作出了坚定的承诺，保证75%的支持率。 为这一提议争取时间，以促进他作为一名独立调查员的职业生涯。

Abstract: Chronic psychosocial stress exposure is a potent but largely under-recognized risk factor for cardiovascular disease (CVD); however, the underlying mechanism remains uncertain. Chronic stress triggers a neurohormo- nal response, but the upstream brain centers initiating this cascade are incompletely defined. Several recent studies have shown that higher stress is associated with increased inflammation that drives CVD. Furthermore, a growing body of research shows a benefit for stress reduction in individuals with CVD via modification of brain activity and reduction of systemic inflammation and CVD symptoms. Advanced imaging with positron emission tomography and magnetic resonance imaging (PET/MRI) provides an opportunity to reproducibly evaluate the neurobiological activity of stress-associated neural centers (e.g., the amygdala) that participate in the initiation of this pathway while concurrently evaluating the activities of several other tissues that may partic- ipate in this mechanism, such as the bone marrow and arterial wall, to derive novel mechanistic insights. Within this paradigm, our group has shown that heightened activity of the amygdala associates with increased bone marrow activity and increased inflammation of the arterial wall. The current proposal addresses these knowledge gaps by assessing the impact of mindfulness-based stress reduction on arterial inflammation (Aim 1) as well as amygdalar activity and systemic inflammation (Aim 2) in individuals with known coronary artery disease using PET/MRI. This randomized controlled trial will enroll 36 subjects randomized to stress reduction or usual care who will undergo baseline and follow-up imaging and inflammatory biomarkers. Subjects with confounding conditions (i.e., psychiatric or neurologic disease, etc.) will be excluded. Dr. Michael Osborne is an Instructor of Medicine at Harvard Medical School and Massachusetts General Hospital (MGH) who is highly qualified and invested in leading this study. He has a unique background in engineering and advanced imaging and a track record of successful research, including publications and awards, using several imaging modalities. Via this proposal, he will develop expertise in multi-system PET/MRI and improve his foundation in the imple- mentation of clinical trials, biostatistics, inflammation biology, stress, and mind-body medicine while generating the data and profile needed to transition to R-level independent NIH-supported research. His long-term goal is to apply multi-parametric PET/MRI to better understand the relationship between stress and physical disease and identify effective treatments. He is supported by a well-qualified mentorship team that is led by Dr. Ahmed Tawakol, a cardiologist with expertise in PET, and includes other NIH-funded investigators in radiology, psychi- atry, epidemiology, and cardiology. His institutional environment is robust and has a long history of supporting the development of early investigators via myriad resources including didactics, facilities, and mentorship. The MGH Division of Cardiology has made a strong commitment to Dr. Osborne with assurance of 75% of pro- tected time for this proposal to foster his career as an autonomous investigator.