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

项目总结/摘要 这是一个指导病人为导向的研究职业发展奖（K23）的应用程序。目标 拟议项目的目的是为候选人提供必要的技能，以发展独立的研究 致力于开发进行性核上性麻痹（PSP）神经影像学生物标志物的项目 和其他阿尔茨海默病相关的痴呆症。为了实现这一长期职业目标，候选人将：1） 识别多模态（体积、结构和功能连接）磁共振成像（MRI） PSP 3种亚型（PSP-Richardson综合征（PSP-RS）、PSP-言语/语言障碍（PSP-Speech/Language Disorder （PSP-SL）和PSP-皮质基底综合征（PSP-CBS）），如最近修订的PSP诊断标准中所述。 标准，以及2）检查这些成像特征与横截面特征之间的关联 1年的临床变化。候选人提出一个全面的培训计划，结合正式 由导师监督的课程作业、会议和辅导，参与应用培训经验，以及 参加研讨会和讲习班。具体培训目标包括：1）神经影像学方法培训 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）论文准备、基金撰写和领导力培训 能力;和5）在负责任的研究行为的持续培训。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。的 主要假设是：1）在PSP-RS中，将有更大的结构和功能 与其他PSP相比，双侧背侧中脑和额纹状体灰质的连接中断 亚型，基线双侧扩散张量成像（DTI）背侧 中脑/静息状态fMRI（rs-fMRI）额纹状体连接和执行功能; 2）在PSP-SL中， 更大的结构和功能的连接中断，在占主导地位的下额叶皮层及其 皮层下言语网络连接，以及基线DTI和rs-fMRI之间的显著相关性 在优势下额叶和语言功能的措施;和3）在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中断 在最受影响的一侧，基线DTI和rs-fMRI测量之间存在显著相关性， 顶叶-背外侧纹状体和实用区。这项研究的结果将用于开发R 01 研究建议，这将有助于候选人的过渡到一个独立的研究人员。

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.