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

基本信息

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
项目类别：
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

项目摘要

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作用引起血管疾病。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。可以观察到，动脉通常会受损，从而导致脑缺血，这是 CUD 中常见的致命结果。事实上，虽然有尸检研究记录了 CUD (iCUD) 个体的动脉疾病，但早期体内检测的滞后会带来灾难性的后果。成像技术用于早期检测无症状人群的动脉粥样硬化 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 (18F-FDG) 可量化动脉粥样硬化斑块中的血管壁炎症，而磁性磁共振成像 (MRI) 与 3 维 (3D) 暗血扫描可表征颈动脉斑块负担。同步最先进的先前验证的 PET/MRI CA 成像从未应用于早期对无症状吸毒者进行动脉粥样硬化检测是针对这一人群进行早期检测。由于“瘾君子一代”（80 年代中期）在经历了数十年的可卡因和毒品滥用之后正在步入老龄化，这一问题尤为紧迫。由于同时吸烟和饮酒，这些 iCUD 患血管疾病的风险特别高，然而，鉴于吸毒成瘾的固有因素，该人群的相关诊断仅存在。当为时已晚而无法干预时才进行（因此事后研究占主导地位）。 CA 动脉粥样硬化标志物将在无症状 iCUD 中检测到，与其可卡因、烟草和饮酒水平与具有已知危险因素的个体中检测到的水平相当，甚至超过患有心血管疾病但无 CUD 的双侧内部 CA 是含氧血液的主要管道。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（尤其是注意力、记忆力和执行功能），最近建议通过大脑网络进行调节连接性（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根据 MPI Alia-Klein 进行的一系列研究，通过静息态功能 MRI 进行测量。和 Goldstein，iCUD 中报告了类似的静息态低效率，并受到药物使用严重程度的调节并且伴随着类似的认知功能障碍，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。该提案首次将颈动脉与药物成瘾中的大脑功能联系起来，它还解决了公共卫生问题一旦病理学被确定，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。特别是如果在早期阶段发现，及时干预可以防止发展为紧急情况，损伤和过早死亡给社会带来巨大成本。