Thalamic MRI, histopathologic, and clinical correlations in multiple sclerosis

多发性硬化症的丘脑 MRI、组织病理学和临床相关性

• 批准号: 10455697
• 负责人: Kedar Mahajan
• 金额: $ 18.43万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10455697
• 关键词: Affect; Anatomy; Anterior; Area; Atlases; Atrophic; Autopsy; Award; Axon; Basic Science; Biological Markers; Biometry; Biostatistical Methods; Brain; Career Choice; Cell Nucleus; Cervical spinal cord structure; Characteristics; Clinic; Clinical; Clinical Research; Clinical Trials; Cognitive; Confocal Microscopy; Data; Data Set; Demyelinations; Dendrites; Dendritic Spines; Development; Disease Progression; Doctor of Philosophy; Ensure; Fellowship; Funding; Future; Goals; Histopathology; Image; Impaired cognition; Impairment; Individual; Injury; Intervention; Label; Laboratories; Lateral; Lateral Geniculate Body; Lesion; Magnetic Resonance Imaging; Measurement; Measures; Medial; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Microglia; Motor; Multiple Sclerosis; Myelin; Nerve Degeneration; Neurons; Neurosciences; Nuclear; Parietal; Pathologic; Pathologic Processes; Pathology; Performance; Persons; Physicians; Physics; Primary Progressive Multiple Sclerosis; Radiology Specialty; Research; Research Personnel; Research Project Grants; Research Proposals; Risk; Scientist; Societies; Spinal Cord; Structure; Supervision; Syndrome; Techniques; Testing; Thalamic Nuclei; Thalamic structure; Thick; Tracer; Training; Visual Acuity; axon injury; axonal degeneration; base; career development; clinical investigation; clinical predictors; cohort; design; disability; gray matter; imaging biomarker; improved; in vivo; insight; lipophilicity; novel; patient oriented; patient oriented research; programs; progressive neurodegeneration; skills; success; translational neuroscience; translational physician; white matter injury; young adult

Project Summary/Abstract The purpose of this K23 Mentored Patient-Oriented Research Career Development Award is to develop Kedar Mahajan MD, PhD as an independent translational neuroscience researcher with a focus in multiple sclerosis (MS). This project will allow him to pursue his research plans in understanding neurodegeneration and progressive disability in MS. The structured mentoring plan for clinical, laboratory, and imaging research with semester-long courses in biostatistics and MRI analysis, will provide for an accelerated development of his independent career path. The candidate’s lab mentor, Dr. Bruce Trapp, is a world renowned neuroscience researcher in MS and will oversee his overall development and develop his basic science proficiency. Dr. Daniel Ontaneda’s expertise in the application of advanced MRI techniques to clinical trials, and Dr. Kunio Nakamura’s background in MRI processing and analysis in clinical investigations, will form critical components of the candidate’s mentorship committee. At the Cleveland Clinic Mellen Center, under the supervision of his clinical mentors Daniel Ontaneda MD, MSc and Jeffrey A. Cohen MD, Dr. Mahajan is nearing the completion of a two year clinical and research MS fellowship (National MS Society Clinician Scientist Development Award). He has already collaborated with Dr. Trapp and begun to characterize thalamic demyelination and neurodegeneration and with Dr. Nakamura to correlate thalamic atrophy with extra-thalamic MRI changes. His preliminary data supports the concept that thalamic demyelination is not common in postmortem brains from individuals with MS, and that thalamic atrophy is driven by extra-thalamic injury. Based on these observations, we decided to further examine thalamic pathology and hypothesized that 1) thalamic atrophy will correlate with extra-thalamic injury in the spinal cord and gray matter injury on MRI; 2) thalamic histopathology will show neuronal, axonal, and dendritic injury and loss; 3) atrophy of individual thalamic nuclei will correspond to injury in their respective afferent and efferent projections in cortical regions on MRI, and will correlate with clinical measures associated with their functions. The aims of the proposed research project are: 1) to examine MRI characteristics correlated with thalamic atrophy; 2) investigate pathological correlates of thalami with extremes in atrophy and thalamic lesions; 3) to determine the relationship between individual thalamic nuclear volumes and clinical disability measures. As the MRI sequences in the post-mortem and in vivo projects are similar, correlations between post-mortem MRI metrics to histopathology (Aim 1), and in vivo MRI metrics to quantitative clinical measures (Aim 2), are feasible and particularly meaningful for future clinical studies. The training and development in this structured mentoring plan is designed to provide Dr. Mahajan the framework to seek independent research program funding near the completion of this award, a step towards his goal of becoming a translational physician scientist in MS.

项目总结/摘要 这个K23指导的以患者为导向的研究职业发展奖的目的是发展 Kedar Mahajan医学博士，博士作为一个独立的翻译神经科学研究人员，专注于多个 硬化症（MS）。这个项目将使他能够继续他的研究计划，了解神经变性 临床、实验室和影像学研究的结构化指导计划 在生物统计学和MRI分析学期的课程，将提供他的加速发展， 独立的职业道路。候选人的实验室导师布鲁斯特拉普博士是世界著名的神经科学家， 研究员在MS，并将监督他的整体发展和发展他的基础科学能力。博士 丹尼尔Ontaneda的专业知识在应用先进的MRI技术的临床试验，和博士国雄 中村在临床研究中的MRI处理和分析方面的背景将成为关键因素 候选人导师委员会的主席 在克利夫兰诊所梅伦中心，在他的临床导师丹尼尔翁塔内达的监督下， MD，MSc和Jeffrey A.科恩医学博士，Mahajan博士即将完成为期两年的临床和研究 MS奖学金（国家MS社会临床科学家发展奖）。他已经与 博士Trapp并开始描述丘脑脱髓鞘和神经退行性变，并与中村博士合作， 将丘脑萎缩与丘脑外MRI改变相关联。他的初步数据支持这样一个概念， 丘脑脱髓鞘在MS患者的死后大脑中并不常见， 萎缩是由丘脑外损伤引起的。 基于这些观察，我们决定进一步检查丘脑病理学，并假设， 1)丘脑萎缩将与脊髓中的丘脑外损伤和MRI上的灰质损伤相关; 2） 丘脑组织病理学将显示神经元、轴突和树突的损伤和损失; 3）个体的萎缩 丘脑核将对应于皮质区域中它们各自的传入和传出投射中的损伤 在MRI上，并且将与与其功能相关的临床测量相关联。建议的目标 本研究的主要目的是：1）研究丘脑萎缩的MRI特征; 2）研究丘脑萎缩的MRI表现， 丘脑与萎缩和丘脑病变的极端病理学相关性; 3）确定 个体丘脑核体积与临床残疾测量之间的关系。由于MRI 尸检和体内项目中的序列相似，尸检MRI指标之间的相关性 组织病理学（目标1）和定量临床测量（目标2）的体内MRI指标是可行的， 对未来的临床研究特别有意义。这种结构化指导的培训和发展 该计划旨在为Mahajan博士提供一个框架，以寻求附近的独立研究项目资金。 该奖项的获得，使他朝着成为密西西比州转化医生科学家的目标又迈出了一步。