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

扩大以患者为中心的大脑、行为和年龄相关痴呆症研究的指导和神经影像专业知识

• 批准号: 10636842
• 负责人: Daniel Oliver Claassen
• 金额: $ 17.1万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-10 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10636842
• 关键词: Academic Medical Centers; Acceleration; Address; Age; Alzheimer' s disease related dementia; Anatomy; Atlases; Award; Behavior; Biodistribution; Biological; Biological Assay; Brain; Brain Stem; Brain region; Clinical; Clinical Research; Clinical assessments; Complement; Contrast Media; Data; Dementia; Dementia with Lewy Bodies; Deposition; Development; Development Plans; Diagnosis; Disease; Disease Progression; Disease model; Dopamine; Early Diagnosis; Ensure; Exhibits; Faculty; Fostering; Goals; Growth; Hippocampus; Human; Image; Imaging Techniques; Institution; Intervention; Iron; K-Series Research Career Programs; Lewy Bodies; Lewy Body Disease; Magnetic Resonance Imaging; Magnetism; Maps; Measurement; Measures; Mentors; Mentorship; Methods; Midcareer Investigator Award in Patient-Oriented Research; Nerve Degeneration; Neurobiology; Neurodegenerative Disorders; Neurologist; Noise; Norepinephrine; Outcome; Parkinson Disease; Parkinsonian Disorders; Participant; Pathologic; Pathology; Patients; Phenotype; Physicians; Pigments; Population; Predisposition; Public Health; Pure Autonomic Failures; REM Sleep Behavior Disorder; Rare Diseases; Research; Research Methodology; Research Personnel; Resolution; Resources; Risk; Scientist; Severities; Signal Transduction; Spatial Distribution; Stratification; Structure; Substantia nigra structure; Symptoms; Techniques; Testing; Therapeutic; Time; Tissues; Training; age related; age related neurodegeneration; alpha synuclein; biomarker development; brain tissue; career; career development; clinical biomarkers; clinical diagnosis; clinical investigation; demented; design; experience; high resolution imaging; high risk; hyposmia; imaging biomarker; imaging modality; improved; in vivo; insight; interest; locus ceruleus structure; motor symptom; nervous system disorder; neuroimaging; neuroimaging marker; neuromelanin; novel; oxidation; pars compacta; participant enrollment; patient oriented research; patient population; predictive modeling; programs; recruit; sex; synucleinopathy; therapeutic effectiveness; ultra high resolution

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.

摘要 这个K24职业中期研究者奖以患者为导向的研究是一个修订。这一目标 一项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 候选人的专业知识。具体来说，这一奖项将确保候选人保护的时间承诺， 对参与临床研究的学员进行持续和扩大的指导工作， 研究，并获得新的成像专业知识，应用定量磁共振成像（MRI） 方法给患有与年龄相关的神经退行性痴呆症的患者。这项建议会 允许研究者将其研究工作扩展到新的患者人群， 在一个计划性研究联盟中工作，并推进临床研究工作，以解决 神经影像学生物标志物。职业发展计划侧重于高领域和超高领域的培训， 现场MRI方法，其中将补充与专家合作者和顾问的动手培训 与研究目标相关的课程。3特斯拉和7特斯拉方法的开发将是 应用于纯自主神经功能衰竭的罕见疾病患者人群，他们可能会转化为痴呆症， 路易体，一种与阿尔茨海默病有关的痴呆症。指导计划旨在帮助 学员成功地发展了他们的学术研究事业。具体而言，指导计划将确保 正在申请K奖（即K23，K 01和K76）的早期神经科医生将有适当的 导师，因为他们开发的研究方法，并建立研究专长。的额外支持 顾问将允许申请人开发一种针对医生的指导方法- 科学家VUMC拥有广泛的机构资源，将确保完成这一目标。最后， 职业发展的重点，开发新的成像技术将促进研究 计划该项目将评估发生在α-突触核蛋白疾病患者中的神经退行性变化。 这些症状包括单纯自主神经功能衰竭的前驱状态，以及帕金森病和痴呆症。 路易体目的是了解铁、神经黑色素和大分子含量的变化 可作为年龄相关性神经退行性疾病的客观影像学生物标志物， 可以量化这些生物学变化的严重性和程度的候选物。通过获取患者的数据 作为自主神经罕见疾病联盟的一部分，候选人可以测试早期 脑干神经黑色素减少、铁沉积增加和高分子含量增加将 鉴定可能从前驱症状转变为中枢α-突触核蛋白紊乱的患者。将MRI数据与 来自详细临床研究的临床观察将允许改进以下预测模型： 疾病转化总的来说，该奖项将为扩大专业知识和指导提供关键支持 申请人的计划。