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: 10259768
• 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/10259768
• 关键词: Academic Medical Centers; Address; Age; Alzheimer' s disease related dementia; Anatomy; Atlases; Award; 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; Enrollment; Ensure; Exhibits; Faculty; Fostering; Goals; Growth; Hippocampus (Brain); Image; Imaging Techniques; Intervention; Iron; K-Series Research Career Programs; Lewy Bodies; Lewy Body Disease; Magnetic Resonance Imaging; Magnetism; 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; Testing; Therapeutic; Time; Tissues; Training; age related; age related neurodegeneration; alpha synuclein; base; biomarker development; brain behavior; brain tissue; career; career development; clinical Diagnosis; clinical biomarkers; clinical investigation; design; experience; high resolution imaging; high risk; human imaging; hyposmia; imaging biomarker; imaging modality; imaging study; improved; in vivo; insight; interest; locus ceruleus structure; magnetic field; motor symptom; nervous system disorder; neuroimaging; neuroimaging marker; neuromelanin; novel; oxidation; pars compacta; 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.

抽象的 K24 以患者为导向的职业生涯中期研究者奖是对该奖项的修订。 提案重点是培养范德比尔特大学医学中心的学员，并扩大研究范围 具体来说，该奖项将确保候选人有时间投入。 对从事以患者为中心的临床研究的学员进行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 该提案将向患有与年龄相关的神经退行性痴呆症的患者提供方法。 允许研究者将他的研究工作扩展到新的患者群体，积累经验 在计划性研究联盟中工作，并推进临床研究工作以解决 职业发展计划侧重于高场和超高场培训。 现场 MRI 方法，其中将补充专家合作者和顾问的实践培训 与研究目标相关的课程作业将是 3 特斯拉和 7 特斯拉方法的开发。 适用于患有纯粹自主神经衰竭的罕见疾病患者群体，他们可能会因以下原因转为痴呆： Lewy Bodies，一种与阿尔茨海默病相关的痴呆症，指导计划旨在重点帮助患者。 具体来说，指导计划将确保受指导者成功发展他们的学术研究生涯。 申请 K 奖（即 K23、K01 和 K76）的早期神经科医生将拥有适当的 在他们开发研究方法和建立研究专业知识时提供指导。 顾问将允许申请人制定适合医生的指导方法- VUMC 拥有广泛的机构资源，这将确保实现这一目标。 该研究将促进开发新成像技术的职业发展重点 计划。该项目将评估 α-突触核蛋白疾病患者发生的神经退行性变化。 这些包括纯粹自主神经衰竭的前驱状态，以及帕金森病和痴呆症 目的是了解铁、神经黑色素和大分子含量的变化。 可用作与年龄相关的神经退行性疾病的客观成像生物标志物，推进成像 通过获取患者数据，可以量化这些生物学变化的严重程度和程度。 作为自主罕见疾病联盟的一部分，候选人可以测试早期的假设 脑干神经黑色素减少、铁沉积增加和大分子含量增加 将 MRI 数据与 MRI 数据相结合，识别可能从前驱期转变为中枢性 α-突触核蛋白疾病的患者。 来自详细临床研究的临床观察将有助于改进预测模型 总体而言，该奖项将为扩大专业知识和指导提供重要支持。 申请人的计划。