Atherosclerosis in cocaine addiction: imaging risk with PET/MR

可卡因成瘾引起的动脉粥样硬化：PET/MR 成像风险

• 批准号: 10624369
• 负责人: Nelly Alia-Klein
• 金额: $ 75.21万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10624369
• 关键词: 3-Dimensional; Accident and Emergency department; Address; Age; Aging; Alcohol consumption; Area; Arterial Fatty Streak; Arteries; Atherosclerosis; Attention; Autopsy; Bilateral; Blood; Blood Vessels; Brain; Brain region; Cardiovascular Diseases; Carotid Arteries; Carotid Artery Diseases; Carotid Artery Plaques; Carotid Stenosis; Cells; Cerebral Ischemia; Cerebral hemisphere; Cessation of life; Chronic; Clinical; Cocaine; Cocaine Dependence; Cocaine use disorder; Cognitive; Complex; Crack Cocaine; Darkness; Detection; Diagnosis; Disease; Disease Marker; Drug Addiction; Drug usage; Early Diagnosis; Emergency Situation; Endothelium; Epidemic; Executive Dysfunction; Fatal Outcome; Functional Magnetic Resonance Imaging; Gender; Generations; Guide prevention; Hybrids; Image; Impaired cognition; Impairment; Individual; Inflammation; Internal carotid artery structure; Intervention; Link; Macrophage; Magnetic Resonance Imaging; Measures; Memory; Memory impairment; Methods; Morbidity - disease rate; Neurologic; Neuropsychological Tests; Pathology; Population; Positron-Emission Tomography; Prefrontal Cortex; Premature Mortality; Process; Proliferating; Public Health; Reporting; Rest; Rewards; Risk; Scanning; Series; Severities; Societies; Structure; Surface; Symptoms; Target Populations; Thick; Time; Tobacco use; Toxic effect; Vascular Diseases; Visit; X-Ray Computed Tomography; aging population; cardiovascular emergency; cardiovascular risk factor; cigarette smoking; cocaine use; cognitive function; cognitive task; comorbidity; cost; craving; drug addict; early detection biomarkers; executive function; fluorodeoxyglucose; functional MRI scan; high risk; in vivo; neural network; new technology; non-invasive imaging; opioid use; pre-clinical; prevent; radiotracer; reward processing; substance use; ultrasound; vascular abnormality; vascular inflammation; vasoconstriction

Cocaine use disorder (CUD) can cause vascular disease mainly through chronic vasoconstriction effects. Atherosclerosis can be present in the carotid artery (CA) even without overt clinical symptoms. Once symptoms are observable, the artery is usually damaged and cerebral ischemia can ensue, a common fatal outcome in CUD. Indeed, while there are postmortem studies documenting arterial disease in individuals with CUD (iCUD), studies for early in-vivo detection lag behind with catastrophic consequences. Here we will leverage the significant advances made in imaging for early detection of atherosclerosis in asymptomatic populations who are nevertheless at increased risk for vascular disease by MPI Fayad; such early detection is crucial for guiding prevention efforts. Specifically, we will use a hybrid scanner whereby positron emission tomography (PET) with the radiotracer 18F- fluorodeoxyglucose (18F-FDG) quantifies vessel-wall inflammation in atherosclerotic plaques while magnetic resonance imaging (MRI) with a 3-dimensional (3D) dark-blood scan characterizes carotid plaque burden. Such simultaneous state-of-the-art previously validated PET/MRI CA imaging has never before been applied for early atherosclerosis detection in asymptomatic drug addicted individuals. Targeting this population for early detection is of particular urgency now that the “Crack generation” (of the mid 80s) is aging. Following decades of cocaine and comorbid tobacco and alcohol use, these iCUD are at an especially high risk for vascular disease and atherosclerosis. Nevertheless, given factors inherent to drug addiction, relevant diagnoses in this population are only made when it is too late to intervene (hence the preponderance of post-mortem studies). We hypothesize that markers of CA atherosclerosis will be detected in asymptomatic iCUD, as related to their cocaine, tobacco, and alcohol use, at levels comparable, or even surpassing, those detected in individuals with known risk factors for cardiovascular disease but without CUD. The bilateral internal CAs are the primary conduits of oxygenated blood to the cerebral hemispheres and indeed individuals with cardiovascular disease demonstrate cognitive decline (especially of attention, memory and executive function), recently suggested to be modulated by brain network connectivity (especially in brain networks innervated by the internal CAs and subserving salience/control and reward processing) as measured by resting-state functional MRI. Following a series of studies conducted by MPIs Alia-Klein and Goldstein, where similar resting-state inefficiencies were reported in iCUD, modulated by severity of drug use and accompanied by similar cognitive dysfunction, here we postulate that the CA disease markers in iCUD will correlate with neural network connectivity and cognitive function. Beyond the mechanistic inventiveness of this proposal, linking of the carotid to brain function for the first time in drug addiction, it also addresses a public health imperative for early detection of the preclinical markers of atherosclerosis in iCUD. Once pathology is identified, and especially if identified at an early stage, timely intervention can prevent the progression into emergencies, impairments and premature mortality that comprise an enormous cost to society.

可卡因使用障碍(CUD)主要通过慢性血管收缩效应导致血管疾病。 动脉粥样硬化可以出现在颈动脉(CA)，即使没有明显的临床症状。一旦症状出现 可见，动脉通常受损，继而可能发生脑缺血，这是CUD常见的致命后果。 事实上，虽然有尸检研究记录了患有CUD(ICUD)的人的动脉疾病，但 早期的体内检测滞后，带来灾难性的后果。在这里，我们将利用重大进展 用于在无症状人群中早期发现动脉粥样硬化的成像技术 MPI Fayad增加了血管疾病的风险；这种早期检测对于指导预防工作至关重要。 具体地说，我们将使用一种混合扫描仪，利用18F放射性示踪剂进行正电子发射断层扫描(PET)- 氟脱氧葡萄糖(18F-FDG)定量动脉粥样硬化斑块的炎症反应 磁共振成像(MRI)与三维(3D)暗血扫描的特征是颈动脉斑块负荷。是这样的 同时最先进的先前验证的PET/MRI CA成像以前从未被应用于早期 无症状吸毒者的动脉粥样硬化检测。针对这一人群进行早期检测 尤其迫在眉睫的是，(80年代中期的)“裂缝生成”正在老化。在经历了几十年的可卡因和 同时使用烟草和酒精，这些iCUD患血管疾病的风险特别高， 动脉硬化。然而，考虑到吸毒成瘾的内在因素，这一人群中的相关诊断仅为 在为时已晚的情况下进行干预(因此尸检研究占主导地位)。我们假设 CA动脉粥样硬化的标志物将在无症状的ICUD中被检测到，这与他们的可卡因、烟草和 饮酒水平，与已知有高血压危险因素的人检测到的水平相当，甚至超过 心血管疾病，但没有CUD。双侧内冠状动脉是含氧血液输送至 大脑半球，甚至心血管疾病患者都表现出认知能力下降。 (尤其是注意力、记忆和执行功能)，最近被认为是由大脑网络调节的 连接性(特别是在由内部CA和从属显著/控制和奖励支配的大脑网络中 处理)，由静息状态功能磁共振测量。在MPIS Alia-Klein进行的一系列研究之后 以及Goldstein，在iCUD中报告了类似的静息状态低效，受药物使用严重程度的影响 伴随着类似的认知功能障碍，我们假设iCUD中的CA疾病标记物将 与神经网络连通性和认知功能相关。除了这种机械性的发明 该提案首次将颈动脉与大脑功能联系在一起，这也解决了公众健康问题 早期检测iCUD动脉粥样硬化的临床前标志物势在必行。一旦确定了病理， 特别是如果在早期阶段发现，及时干预可以防止事态发展为紧急情况， 损伤和过早死亡构成了巨大的社会代价。