Multi-modal magnetic resonance imaging in progressive supranuclear palsy (PSP)

项目摘要/摘要 这是一份申请以患者为导向的导师研究职业发展奖(K23)的申请书。目标是 拟议项目的目的是为候选人提供开展独立研究所需的技能 致力于发展进行性核上性麻痹(PSP)神经影像生物标记物的项目 以及其他与阿尔茨海默病相关的痴呆症。为了促进这一长期的职业目标，应聘者将：1) 确定多模式(体积、结构和功能连接)磁共振成像(MRI) 三种PSP亚型(PSP-Richardson综合征(PSP-RS)、PSP-言语障碍)的差异 (PSP-SL和PSP-皮质基综合征(PSP-CBS))，如最近修订的PSP诊断 标准，以及2)检查这些成像特征与横断面特征之间的关联 1年的临床变化。应聘者提出一个全面的培训计划，结合正式的 课程作业、会议和由导师指导的教程，参与应用培训体验，以及 参加研讨会和研讨会。具体培训目标包括：1)神经成像方法培训 和图像分析；2)实验研究设计和统计分析的高级培训；3)高级 临床试验方法学培训；4)手稿准备、赠款撰写和领导能力培训 能力；以及5)在负责任的研究行为方面的持续培训。培训计划将是 根据申请人收集的初步数据，与研究项目协调实施。这个 要检验的主要假设是：1)在PSP-RS中，将有更多的结构和功能 与其他PSP相比，双侧中脑背侧和额纹状体灰质的连接性障碍 亚型和基线双侧弥散张量成像(DTI)背侧之间的显著相关性 中脑/静息状态-功能磁共振成像(rS-fMRI)额纹状体连接和执行功能；2)在PSP-SL中， 在占优势的额叶下部皮质及其周围脑区的结构和功能连接性障碍 皮层下语言网络连接，以及基线DTI和RS-fMRI之间的显著关联 3)在PSP-CBS中，PSP-CBS将有更大的 对侧顶叶-背外侧纹状体网络的结构和功能连接障碍 到受影响最严重的一侧，以及基线DTI和RS-fMRI测量之间的显著关联 顶叶背外侧纹状体和背侧纹状体。这项研究的结果将用于开发R01 有助于候选人向独立研究人员过渡的研究提案。

PROJECT SUMMARY/ABSTRACT This is an application for a Mentored Patient-Oriented Research Career Development Award (K23). The goal of the proposed project is to provide the candidate with skills necessary to develop an independent research program dedicated to the development of neuroimaging biomarkers in Progressive Supranuclear Palsy (PSP) and other Alzheimer disease-related dementias. To facilitate this long-term career goal the candidate will: 1) identify multimodal (volumetric, structural and functional connectivity) magnetic resonance imaging (MRI) differences among 3 PSP subtypes (PSP-Richardson syndrome (PSP-RS), PSP-Speech/Language Disorder (PSP-SL), and PSP-Corticobasal syndrome (PSP-CBS)) as delineated in the recently revised PSP diagnostic criteria, and 2) examine the associations between these imaging features with cross-sectional characteristics and 1-year clinical change. The candidate proposes a comprehensive training plan, combining formal coursework, meetings and tutorials overseen by his mentors, participation in applied training experiences, and involvement in seminars and workshops. Specific training goals include: 1) training in neuroimaging methods and image analysis; 2) advanced training in experimental study design and statistical analysis; 3) advanced training in clinical trials methodology; 4) training in manuscript preparation, grant writing and leadership capability; and 5) continued training in the responsible conduct of research. The training plan will be implemented in coordination with a research project based on preliminary data collected by the applicant. The primary hypotheses to be examined are: 1) In PSP-RS, there will be greater structural and functional connectivity disruptions in bilateral dorsal midbrain and frontostriatal gray matter compared with other PSP subtypes, and significant associations between baseline bilateral diffusion tensor imaging (DTI) dorsal midbrain/resting state-fMRI (rs-fMRI) frontostriatal connectivity and executive function; 2) In PSP-SL, there will be greater structural and functional connectivity disruptions in the dominant inferior frontal cortex and its subcortical speech network connections, and significant associations between baseline DTI and rs-fMRI measures in the dominant inferior frontal lobe and language function; and 3) In PSP-CBS, there will be greater structural and functional connectivity disruptions in the parietal lobe-dorsolateral striatum network contralateral to the most affected side, and significant associations between baseline DTI and rs-fMRI measures in the parietal lobe-dorsolateral striatum and praxis. Results from this research will be used to develop a R01 research proposal that will facilitate the candidate’s transition to an independent researcher.