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：
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
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/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

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

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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）可能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，动脉粥样硬化也可能存在于颈动脉（CA）中。一旦症状可观察到的动脉通常会受损，并且可能随之而来的脑缺血，这是CUD中常见的致命结果。确实，尽管有验尸研究记录了患有cud的人（ICUD）的人工制品，但研究体内检测早期落后于灾难性后果。在这里，我们将利用重大进步在成像中以早期检测到不对称人群的动脉粥样硬化的成像。 MPI Fayad增加血管疾病的风险；这种早期发现对于指导预防工作至关重要。具体而言，我们将使用混合扫描仪，从而将极性发射断层扫描（PET）与radiotracer 18f- 荧光脱氧葡萄糖（18F-FDG）量化了动脉粥样硬化斑块中的血管壁注射，而磁性共振成像（MRI）具有3维（3D）的漆黑扫描字符颈动脉斑块负担。这样的简单的先前验证的宠物/MRI CA成像从未提早应用在不对称药物中发现的动脉粥样硬化检测。针对该人群以提早发现是现在，（80年代中期）的“裂纹产生”正在衰老，特别是紧迫的。经过数十年的可卡因和合并烟草和酒精使用，这些ICUD对血管疾病和动脉粥样硬化。然而，给定吸毒固有的因素，该人群中的相关诊断仅是干预为时已晚（因此是验尸研究的优势）。我们假设这一点在无症状的ICUD中将检测到CA动脉粥样硬化的标记，与可卡因，烟草和饮酒，在具有可比甚至超过的水平上，在具有已知风险因素的个体中检测到的饮酒水平心血管疾病，但没有CUD。双边内CAS是氧化血的主要导管脑半球，实际上患有心血管疾病的人表现出认知能力下降（特别是注意力，记忆和执行功能），最近建议通过大脑网络调节连通性（尤其是在由内部CAS支配的大脑网络中，并掩盖了显着性/控制和奖励通过静止状态功能MRI测量的处理）。遵循MPIS Alia-Klein进行的一系列研究戈德斯坦（Goldstein 并通过类似的认知功能障碍完成，在这里我们假设ICUD中的CA疾病标志物将会与神经网络连通性和认知功能相关。超越了这一机械创造力提案，颈动脉与大脑功能的联系首次在吸毒中，它也解决了公共卫生必须早期检测ICUD动脉粥样硬化的临床前标记。一旦确定病理，特别是如果在早期发现，及时干预可以防止进展成为紧急情况，损害和过早死亡人数包括对社会的巨大成本。