Expanding Mentorship and Neuroimaging Expertise in Patient-Oriented Studies of Brain, Behavior, and Age-Related Dementias

摘要 这个K24职业生涯中期研究人员奖是以患者为中心的研究的修订版。这样做的目的是 提案的重点是在范德比尔特大学医学中心培养学员，并扩大研究范围 候选人的专业知识。具体地说，这一奖项将确保候选人受到保护的时间承诺 参与以患者为中心的临床研究的指导对象的持续和扩大的指导工作 研究并获得应用定量磁共振成像(MRI)的新成像专业知识 方法对患有老年性神经退行性痴呆的患者进行治疗。这项提议将 允许研究人员将他的研究工作扩展到新的患者群体，发展经验 在计划性研究联盟中工作，并推动临床研究努力以解决 神经成像生物标志物。《职业发展计划》注重高场超高能人才培养 现场核磁共振方法，其中将补充与专家合作者和顾问的实践培训 课程内容与研究目标相关。3特斯拉和7特斯拉方法的开发将是 适用于患有纯自主神经衰竭的罕见疾病患者群体，他们可能会转变为痴呆症 路易体，一种与阿尔茨海默病相关的痴呆症。指导计划的设计重点是帮助 学员成功地发展了他们的学术研究事业。具体地说，指导计划将确保 正在申请K奖的早期神经科医生(即K23、K01和K76)将有适当的 在他们开发研究方法和建立研究专业知识的过程中提供指导。来自以下方面的其他支持 顾问将允许申请者制定一种为医生量身定做的指导方法- 科学家。VUMC拥有广泛的机构资源，这将确保完成这一目标。最后， 这项研究将促进开发新成像技术的职业发展重点 计划一下。该项目将评估阿尔法-突触核蛋白紊乱患者的神经退行性变化。 这些包括纯自主神经衰竭的前驱状态，以及帕金森氏症和痴呆症 带着刘易体。目的是了解铁、神经黑色素和大分子含量是如何变化的。 可作为与年龄相关的神经退行性疾病的客观影像生物标志物，推进影像 可以量化这些生物变化的严重程度和程度的候选者。通过获取患者的数据 谁是自主神经罕见疾病联盟的一部分，候选人就可以检验这样的假设 脑干神经黑色素的减少、铁沉积的增加和大分子含量的增加将 确定可能从前驱症状转变为中枢性α-突触核蛋白紊乱的患者。将MRI数据与 来自详细临床调查的临床观察将使预测模型得到改进。 疾病转化。总体而言，该奖项将为扩大专业知识和指导提供关键支持 申请者的计划。

ABSTRACT This K24 Midcareer Investigator Award in Patient-Oriented Research is a revision. The objectives of this proposal focus on developing mentees at Vanderbilt University Medical Center, and expanding the research expertise of the candidate. Specifically, this award will ensure that the candidate protected time to commit to ongoing and expanded mentoring efforts of mentees engaging in clinical research that focuses patient-oriented research, and acquire new imaging expertise that applies quantitative magnetic resonance imaging (MRI) methods to patients who suffer from age-related neurodegenerative dementing disorders. This proposal will allow the investigator to expand his research efforts into a new patient population, develop experience with working in a programmatic research consortium, and advance clinical research efforts to addressing neuroimaging biomarkers. The Career Development Plan focuses on training in high-field and ultra-high- field MRI methods, where hands on training with expert collaborators and consultants will be supplemented with coursework pertinent to the research objectives. Development in 3 tesla and 7 tesla methods will be applied to a rare disease patient population with pure autonomic failure, who may convert to dementia with Lewy Bodies, an Alzheimer Disease-related dementia. The Mentoring Plan is designed to focus on helping mentees succeed in developing their academic research career. Specifically, the mentoring plan will ensure that early stage neurologists who are applying for K-awards (i.e. K23, K01, and K76) will have appropriate mentorship as they develop research methodologies, and build research expertise. Additional support from consultants will allow the applicant to develop of a mentoring approach that is tailored to the physician- scientist. There are extensive institutional resources at VUMC which will ensure completion of this goal. Finally, the career development focus which develops new imaging techniques will be facilitated by the Research Plan. This project will assess neurodegenerative changes that occur in patient with alpha-synuclein disorders. These include the prodromal state of pure autonomic failure, as well as Parkinson’s disease, and Dementia with Lewy bodies. The aim is to understand how changes to iron, neuromelanin, and macromolecular content can be used as objective imaging biomarkers of age-related neurodegenerative diseases, advancing imaging candidates that can quantitate severity and extent of these biologic changes. By acquiring data on patients who are part of the Autonomic Rare Disease Consortium, the candidate can test the hypothesis that early reductions in brainstem neuromelanin, elevated iron deposition, and elevated macromolecular content will identify patients likely to convert from prodromal to central alpha-synuclein disorders. Integrating MRI data with clinical observations from the detailed clinical investigations will allow improvements to prediction models of disease conversion. Overall, this award will provide crucial support for to expand the expertise and mentoring program of the applicant.