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.

项目概要/摘要 本 K01 申请中描述的研究和培训计划将为候选人提供 成为一名独立研究者了解神经退行性疾病性别差异的必要技能 （即小胶质细胞和白质束）和酒精使用障碍（AUD）中的神经认知来识别新的 解决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）成像检查神经认知的性别差异 AUD 中小胶质细胞水平性别差异背后的功能； (2)扩散张量磁共振 成像（DTI）检查白质束完整性的性别差异（AUD）； (3) PET和DTI 多模态整合分析以确定小胶质细胞水平、白质束之间的关系 患有 AUD 的女性和男性的完整性和神经认知功能。六十人（15 名男性和 15 名女性） 持有澳元且 30 名年龄、性别和吸烟情况相匹配的健康对照者将同时参加 PET 和 DTI 扫描以促进 PET、DTI 和 PET/DTI 集成分析。系统地识别性别差异 为了了解白质束完整性的模式，考生还将检查来自大型存档的数据， 神经影像 DTI 数据集（人类连接组项目），以在期间生成出版物和生产力 数据收集。这种新颖的数据收集和二次数据分析的结合旨在 通过提供以下方面的实践经验，最大限度地提高候选人的培训：（1）理论和行为 她自己在公认专家的指导下进行的综合多模式神经影像研究；并且，(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 提议在四个主要领域进行进一步培训：(1) AUD 的神经生物学，(2) 治疗 AUD 的结果研究和临床相关性，(3) DTI 和多模式神经影像学，以及 (4) 生物统计 接近。 K01机制提供的机会将使候选人能够踏上 严格、结构化的 5 年培训和研究计划，旨在为她提供必要的技能 在上面强调的四个领域。该学习计划将结合正式的教学课程，指导 阅读、一对一辅导、专业研讨会、参加科学研究会议，以及 指导研究经验。本 K01 中提出的研究和培训提供了理想的 实现候选人成为独立的长期职业目标的跨学科机会 特别关注性别作为 AUD 神经生物学中的生物变量的科学家。团队由 导师和合作者都是这些领域的领导者，并且具有激励性和协作性 耶鲁大学医学院的环境，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研究领域的独立职业生涯。