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: 10444369
• 负责人: Nelly Alia-Klein
• 金额: $ 75.91万
• 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/10444369
• 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; 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; Magnetic Resonance Imaging; Measures; Memory; Memory impairment; Methods; Morbidity - disease rate; Neurologic; Neuropsychological Tests; Pathology; Pharmaceutical Preparations; Population; Positron-Emission Tomography; Prefrontal Cortex; Premature Mortality; Process; 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; executive function; fluorodeoxyglucose; functional MRI scan; high risk; in vivo; invention; macrophage; neural network; new technology; non-invasive imaging; opioid use; pre-clinical; prevent; radiotracer; reward processing; substance use; time 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.

血管紧张素使用障碍（CUD）主要通过慢性血管收缩效应引起血管疾病。 即使没有明显的临床症状，颈动脉（CA）也可能存在动脉粥样硬化。一旦症状 在可观察到的情况下，动脉通常受损，随后可发生脑缺血，这是CUD中常见的致命结局。 事实上，虽然有尸检研究记录了CUD（iCUD）患者的动脉疾病，但对 早期体内检测滞后，带来灾难性后果。在这里，我们将利用 用于早期发现动脉粥样硬化的无症状人群， MPI Fayad的血管疾病风险增加;这种早期发现对于指导预防工作至关重要。 具体来说，我们将使用混合扫描仪，其中正电子发射断层扫描（PET）与放射性示踪剂18F- 氟脱氧葡萄糖（18 F-FDG）在磁性时量化动脉粥样硬化斑块中的血管壁炎症 具有三维（3D）暗血扫描的共振成像（MRI）表征颈动脉斑块负荷。等 同时进行的最先进的先前验证的PET/MRI CA成像以前从未应用于早期诊断。 无症状药物成瘾个体的动脉粥样硬化检测。针对这一人群进行早期检测， 特别紧迫的是，现在“裂纹一代”（80年代中期）正在老化。在数十年的可卡因和 合并吸烟和饮酒，这些iCUD血管疾病的风险特别高， 动脉粥样硬化然而，考虑到药物成瘾的固有因素，这一人群中的相关诊断仅 在干预为时已晚的情况下进行（因此事后研究占优势）。我们假设 CA动脉粥样硬化的标志物将在无症状iCUD中检测到，与他们的可卡因、烟草和 酒精使用水平与已知危险因素的个人中检测到的水平相当，甚至超过 心血管疾病，但没有CUD。双侧颈内动脉是氧合血的主要通道， 大脑半球以及患有心血管疾病的个体表现出认知能力下降 （特别是注意力、记忆和执行功能），最近提出受脑网络调节 连接性（特别是在受内部CA支配并促进显着性/控制和奖励的大脑网络中 通过静息状态功能性MRI测量。在MPI Alia-Klein进行了一系列研究之后， 和Goldstein，iCUD中报告了类似的静息状态无效，受药物使用严重程度的影响 并伴有类似的认知功能障碍，在这里我们假设iCUD中的CA疾病标志物将 与神经网络连接和认知功能相关。除了机械的创造性之外， 这项提案首次将颈动脉与大脑功能联系起来，这也是一项公共健康问题。 这对于早期检测iCUD中动脉粥样硬化的临床前标志物至关重要。一旦确定了病理学， 特别是如果在早期发现，及时干预可以防止发展成紧急情况， 造成社会巨大代价。