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.

抽象的 这项K24中级护理研究员授予以患者为导向的研究是一项修订版。目标的目标 提案重点是在范德比尔特大学医学中心开发月经，并扩大研究 候选人的专业知识。具体而言，该裁决将确保候选人受到保护的时间 从事临床研究的月经的持续和扩大的心理工作，以患者为导向 研究，并获得应用定量磁共振成像（MRI）的新成像专业知识 与年龄相关的神经退行性痴呆症患者的方法。该提议将 允许研究人员将研究工作扩展到新的患者人群，发展经验 在一个程序化研究联盟中工作，并提高临床研究工作来解决 神经影像生物标志物。职业发展计划的重点是高场和超高的培训 现场MRI方法，将补充与专家合作者和顾问进行培训 与研究目标有关的课程工作。 3种特斯拉和7种特斯拉方法的开发将是 适用于具有纯自主衰竭的罕见病患者人群，他们可能会转化为痴呆症 路易尸体，阿尔茨海默氏病有关的痴呆症。指导计划旨在专注于帮助 Menets成功地发展了他们的学术研究生涯。具体而言，修补计划将确保 那些正在申请K-awards的早期神经科医生（即K23，K01和K76）将有适当的 在开发研究方法并建立研究专业知识的过程中识别。来自 顾问将允许申请人开发一种针对身体的心理方法 - 科学家。 VUMC有大量的机构资源，这将确保完成此目标。最后， 这项研究将准备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。 其中包括纯自主衰竭以及帕金森氏病和痴呆症的前驱状态 与路易的身体。目的是了解如何改变铁，神经苯胺和大分子含量 可以用作与年龄有关的神经退行性疾病的客观成像生物标志物 可以量化这些生物学变化严重程度和程度的候选人。通过获取患者的数据 候选人是自主罕见疾病财团的一部分，可以检验以下假设。 减少脑干神经元素，铁沉积升高和大分子含量的升高将 鉴定可能从前瞻性转变为中央α-突触核蛋白疾病的患者。将MRI数据与 详细的临床研究中的临床观察结果将允许改进预测模型 疾病转化。总体而言，该奖项将为扩大专业知识和心理发展提供重要的支持 申请人的计划。