PET/MRI of the brain-hematopoiesis-atherosclerosis axis in PTSD patients

PTSD 患者脑-造血-动脉粥样硬化轴的 PET/MRI

• 批准号: 10116451
• 负责人: Zahi A. Fayad
• 金额: $ 62.32万
• 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: 2017-03-17 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10116451
• 关键词: Age; Amygdaloid structure; Anatomy; Anterior; Anti-Inflammatory Agents; Aortitis; Arterial Fatty Streak; Arteries; Atherosclerosis; Biological; Biological Markers; Blood; Bone Marrow; Boston; Brain; Brain imaging; Carotid Arteries; Cause of Death; Cell Proliferation; Cells; Chronic; Chronic Post Traumatic Stress Disorder; Clinical; Clinical Research; Collaborations; Control Groups; DSM-V; Data; Diffusion Magnetic Resonance Imaging; Emotional Stress; Enrollment; Exposure to; Fluorescence-Activated Cell Sorting; Fostering; Foundations; Fright; Functional Magnetic Resonance Imaging; Gender; Hematopoiesis; Hematopoietic; Hematopoietic System; Hematopoietic stem cells; Human; Image; Imaging Techniques; Immunologics; Individual; Inflammation; Inflammatory; Link; Lipids; Magnetic Resonance Imaging; Matched Group; Measures; Medical; Mus; Myocardial Infarction; Neurologic; New York; Organ; Participant; Pathway interactions; Patients; Perception; Pharmaceutical Preparations; Positron-Emission Tomography; Post-Traumatic Stress Disorders; Process; Program Research Project Grants; Psychosocial Stress; Recording of previous events; Research; Research Personnel; Resolution; Rest; Risk; Spleen; Stress; Stroke; Structure; Study Subject; System; Systems Biology; Time; Trauma; Work; cardiovascular disorder risk; cardiovascular imaging; cingulate cortex; circulating biomarkers; clinical center; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; high risk; inflammatory marker; innovation; macrophage; migration; neuroimaging; novel; psychosocial; quantitative imaging; recruit; stress disorder; systemic inflammatory response; trauma exposure; traumatic event; urban setting; vascular inflammation; volunteer; white matter

SUMMARY Atherosclerosis and its consequences are the most common causes of death worldwide. Lipid accumulation and associated inflammatory processes are critical to atherosclerosis progression. Investigators from Projects 1 and 2 recently observed that chronic psychosocial stress accelerates hematopoiesis and promotes inflammation in atherosclerotic mice. It is currently unknown if this is relevant in humans. Post-traumatic stress disorder (PTSD), triggered by exposure to extreme traumatic events, is associated with elevated circulating markers of inflammation and higher risk for MI. PTSD patients therefore provide a unique opportunity to study the mechanisms linking chronic psychosocial stress and atherosclerosis. In Project 3 we will employ innovative PET combined with magnetic resonance imaging (PET/MRI) to simultaneously study the hematopoietic system, the artery wall, and the brain's fear system, which comprises the amygdala and anterior cingulate cortex (ACC), to elucidate the relationship between psychosocial stress and systemic inflammation/atherosclerosis in a two center clinical study looking at: I) individuals with PTSD, II) individuals without PTSD but with exposure to severe psychosocial trauma (Trauma Control), and III) matched volunteers with neither PTSD nor exposure to trauma (Healthy Control). Participants in the three study groups, recruited from urban settings in New York and Boston, will be group-matched by age, gender, and Framingham risk scores (FRS). We will recruit 80 subjects in each group and in Aim 1, investigate the relationship between PTSD and atherosclerotic inflammation and burden measured by PET/MRI. In Aim 2, we will examine the relationships between brain's fear circuit responsiveness to threat assessed by functional MRI (fMRI) and white matter integrity assessed by diffusion tensor imaging (DTI) and relate these data to hematopoietic system activation, and vascular inflammation measured by fluorodeoxyglucose (FDG)-PET and atherosclerotic burden measured by MRI. Additionally these parameters will also be related to blood hematopoietic progenitor migration measured using multiparametric fluorescence-activated cell sorting (FACS). Together, these data will provide a very unique picture of the multi-system link between the human brain, hematopoietic organs, inflammatory cells, and the artery wall.

总结 动脉粥样硬化及其后果是全世界最常见的死亡原因。脂质积累 和相关的炎症过程对动脉粥样硬化的进展是至关重要的。项目调查员 1和2最近观察到，慢性心理社会压力加速造血，并促进 动脉粥样硬化小鼠的炎症。目前尚不清楚这是否与人类有关。创伤后应激 创伤后应激障碍（PTSD），由暴露于极端的创伤事件触发，与升高的循环有关。 炎症标志物和心肌梗死的高风险。因此，创伤后应激障碍患者提供了一个独特的机会， 慢性心理社会压力和动脉粥样硬化的联系机制。在项目3中，我们将采用 创新的PET与磁共振成像（PET/MRI）相结合，以同时研究 造血系统，动脉壁，和大脑的恐惧系统，其中包括杏仁核和前 扣带皮层（ACC），以阐明心理社会应激与系统性 炎症/动脉粥样硬化在两个中心的临床研究中观察：I）患有PTSD的个体，II）个体 没有PTSD但暴露于严重的心理社会创伤（创伤控制），和III）匹配的志愿者 既无创伤后应激障碍也无创伤暴露（健康对照组）。三个研究组的参与者， 来自纽约和波士顿的城市环境，将按年龄、性别和乳腺癌风险进行分组匹配。 分数（FRS）。我们将在每组中招募80名受试者，并在目标1中，调查 通过PET/MRI测量PTSD和动脉粥样硬化炎症和负荷。在目标2中，我们将检查 功能性磁共振成像（fMRI）评估的大脑恐惧回路对威胁的反应性与白色 通过扩散张量成像（DTI）评估物质完整性，并将这些数据与造血系统相关 激活和通过氟脱氧葡萄糖（FDG）-PET测量的血管炎症和动脉粥样硬化负荷 通过MRI测量。此外，这些参数还将与血液造血祖细胞有关 使用多参数荧光激活细胞分选（FACS）测量迁移。这些数据将 提供了一个非常独特的画面，人类大脑，造血器官， 炎症细胞和动脉壁