Sex Differences in Alcohol Use Disorder Neurodegeneration using Multimodal PET and DTI Neuroimaging

使用多模态 PET 和 DTI 神经影像学研究酒精使用障碍神经变性的性别差异

• 批准号: 10525013
• 负责人: Yasmin Zakiniaeiz
• 金额: $ 17.61万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-10 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10525013
• 关键词: Address; Age; Alcohol consumption; Alcohols; Archives; Area; Axon; Binding; Biological; Biometry; Brain; Brain imaging; Cerebellum; Clinical; Corpus Callosum; Data; Data Analyses; Data Collection; Data Set; Demyelinations; Diffusion; Disease; Educational workshop; Female; Fiber; Functional disorder; Goals; Growth; Hippocampus (Brain); Human; Impairment; Individual; Lead; Magnetic Resonance Imaging; Measures; Memory impairment; Mentored Research Scientist Development Award; Mentors; Microglia; Modeling; Molecular; Nerve Degeneration; Neurobiology; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neurosciences; Outcomes Research; Pattern; Play; Positron-Emission Tomography; Pre-Clinical Model; Prefrontal Cortex; Productivity; Proteins; Publications; Reading; Recovery; Research; Research Design; Research Personnel; Research Training; Role; Sampling; Scanning; Scientist; Sex Differences; Short-Term Memory; Smoking; Structure; Supervision; Time; Training; Training Programs; Treatment outcome; Woman; addiction; alcohol abuse therapy; alcohol consequences; alcohol use disorder; axon injury; base; brain cell; career; collaborative environment; connectome; design; executive function; experience; imaging study; improved; in vivo; innovation; male; medical schools; men; multimodal neuroimaging; multimodality; neuroimaging; neuromechanism; novel; programs; radiotracer; restoration; sex; skills; symposium; theories; white matter

Project Summary/Abstract The program of research and training described in this K01 application will provide the candidate with the requisite skills to become an independent investigator understanding sex differences in neurodegeneration (i.e., microglia and white matter tracts) and neurocognition in alcohol use disorder (AUD) to identify novel treatment targets that address sex differences. The research component of this 5-year plan involves the application of: (1) positron emission tomography (PET) imaging to examine sex differences in neurocognitive function that underlie sex differences in microglia levels in AUD; (2) diffusion tensor magnetic resonance imaging (DTI) to examine sex differences in white matter tract integrity in AUD and; (3) PET and DTI multimodal integration analysis to determine the relationship between microglia levels, white matter tract integrity, and neurocognitive function in women and men with AUD. Sixty (15 male and 15 female) individuals with AUD and 30 age-, sex-, and smoking-matched healthy controls will participate in both PET and DTI scanning to facilitate PET, DTI, and PET/DTI integration analysis. To systematically identify sex differences in patterns of white matter tract integrity, the candidate will also examine data from a large, archived, neuroimaging DTI dataset (The Human Connectome Project), to generate publications and productivity during data collection. This combination of novel data collection and secondary data analyses is designed to maximize the candidate's training via provision of hands-on experience in both: (1) the theory and conduct of her own combined multimodal neuroimaging study under guided supervision of recognized experts; and, (2) the analysis and interpretation of large-scale neuroimaging datasets. In pursuit of these goals, the candidate proposes to undertake further training in four primary areas: (1) the neurobiology of AUD, (2) treatment outcomes research and clinical corelates of AUD, (3) DTI and multimodal neuroimaging, and (4) biostatistical approaches. The opportunities afforded by the K01 mechanism would enable the candidate to embark on a rigorous, structured 5-year program of training and research, designed to provide her with the necessary skills in the four areas highlighted above. This program of study will combine formal didactic courses, directed readings, one-on-one tutorials, specialized workshops, attendance of scientific research conferences, and mentored research experience. The research and training proposed in this K01 provides an ideal interdisciplinary opportunity to achieve the candidate's long-term career goal of becoming an independent scientist with a particular focus on sex as a biological variable in the neurobiology of AUD. The team of mentors and collaborators are leaders in these fields and, together with the stimulating and collaborative environment of the Yale School of Medicine, will facilitate the candidate's growth and prepare her for an independent career at the interface of AUD neuroscience and neuroimaging research.

项目总结/摘要 本K 01申请中描述的研究和培训计划将为候选人提供 必要的技能，成为一个独立的研究人员了解神经变性的性别差异 (i.e.,小胶质细胞和白色物质束）和酒精使用障碍（AUD）的神经认知，以确定新的 针对性别差异的治疗目标。该五年计划的研究部分涉及 应用：（1）正电子发射断层扫描（PET）成像检查神经认知功能的性别差异 AUD中小胶质细胞水平性别差异的基础功能;（2）扩散张量磁共振 DTI检查AUD中白色物质束完整性的性别差异;（3）PET和DTI 多模式整合分析，以确定小胶质细胞水平、白色物质束 完整性和神经认知功能。60人（15男15女） AUD患者和30名年龄、性别和吸烟匹配的健康对照者将参加PET和DTI 扫描以便于PET、DTI和PET/DTI集成分析。为了系统地确定性别差异， 白色物质束完整性的模式，候选人还将检查来自大型，存档， 神经成像DTI数据集（人类连接组项目），以在 数据收集。这种新数据收集和二级数据分析的结合旨在 通过提供以下两方面的实践经验，最大限度地提高候选人的培训：（1）理论和行为 在公认专家的指导监督下，她自己进行的多模式神经影像学联合研究;以及，（2） 大规模神经影像数据集的分析和解释。为了实现这些目标，候选人 建议在四个主要领域进行进一步的培训：（1）AUD的神经生物学，（2）治疗 AUD的结局研究和临床相关性，（3）DTI和多模式神经成像，以及（4）生物统计学 接近。K 01机制提供的机会将使候选人能够开始一项 严格的，结构化的5年培训和研究计划，旨在为她提供必要的技能 在上述四个方面。这项研究计划将结合联合收割机正式的教学课程，指导 阅读，一对一辅导，专业研讨会，参加科学研究会议， 指导研究经验。本K 01中提出的研究和培训提供了一个理想的 跨学科的机会，以实现候选人的长期职业目标，成为一个独立的 科学家特别关注性作为AUD神经生物学中的生物变量。团队 导师和合作者是这些领域的领导者， 耶鲁医学院的环境，将促进候选人的成长，并为她做好准备。 在AUD神经科学和神经影像学研究的接口独立的职业生涯。