Characterizing axonal damage in multiple sclerosis using TractCaliber MRI

使用 TractCaliber MRI 表征多发性硬化症的轴突损伤

• 批准号: 9886287
• 负责人: Susie Yi Huang
• 金额: $ 13.91万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9886287
• 关键词: Address; Advisory Committees; Autopsy; Award; Axon; Biological; Boston; Brain; Caliber; Central Nervous System Degenerative Diseases; Clinic; Clinical; Clinical Trials; Corpus Callosum; Corticospinal Tracts; Demyelinating Diseases; Demyelinations; Development; Development Plans; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Education; Educational workshop; Fostering; Funding; Future; Goals; Grant; Health; Histopathology; Human; Image; Imaging Techniques; Imaging technology; Impaired cognition; Inflammatory; Injury; Institution; Lead; Lesion; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mentors; Modeling; Multiple Partners; Multiple Sclerosis; Multiple Sclerosis Lesions; Neurologic; Outcome; Outcome Measure; Pathogenesis; Pathologic; Pathology; Patient Care; Patient Recruitments; Patients; Positioning Attribute; Preparation; Research; Research Personnel; Research Proposals; Resources; Severities; Specificity; Techniques; Time; Tissue Banks; Tissue Sample; Training; Translating; Translations; Treatment Effectiveness; Universities; Validation; Work; axon injury; bioimaging; brain tissue; career development; clinical translation; cognitive function; connectome; density; design; disability; imaging biomarker; imaging modality; improved; in vivo imaging; insight; multiple sclerosis patient; nervous system disorder; neuroimaging; non-invasive imaging; novel; patient population; physically handicapped; prevent; programs; progressive neurodegeneration; public health relevance; research clinical testing; response; technology development; white matter; young adult; Address; Advisory Committees; Autopsy; Award; Axon; Biological; Boston; Brain; Caliber; Central Nervous System Degenerative Diseases; Clinic; Clinical; Clinical Trials; Corpus Callosum; Corticospinal Tracts; Demyelinating Diseases; Demyelinations; Development; Development Plans; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Education; Educational workshop; Fostering; Funding; Future; Goals; Grant; Health; Histopathology; Human; Image; Imaging Techniques; Imaging technology; Impaired cognition; Inflammatory; Injury; Institution; Lead; Lesion; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mentors; Modeling; Multiple Partners; Multiple Sclerosis; Multiple Sclerosis Lesions; Neurologic; Outcome; Outcome Measure; Pathogenesis; Pathologic; Pathology; Patient Care; Patient Recruitments; Patients; Positioning Attribute; Preparation; Research; Research Personnel; Research Proposals; Resources; Severities; Specificity; Techniques; Time; Tissue Banks; Tissue Sample; Training; Translating; Translations; Treatment Effectiveness; Universities; Validation; Work; axon injury; bioimaging; brain tissue; career development; clinical translation; cognitive function; connectome; density; design; disability; imaging biomarker; imaging modality; improved; in vivo imaging; insight; multiple sclerosis patient; nervous system disorder; neuroimaging; non-invasive imaging; novel; patient population; physically handicapped; prevent; programs; progressive neurodegeneration; public health relevance; research clinical testing; response; technology development; white matter; young adult

 DESCRIPTION (provided by applicant): In this application, I propose a project of technology development, validation, and translation aimed at providing a better imaging marker of axonal damage in patients with multiple sclerosis (MS). This award will provide protected research time and training in preparation for independent R01 funding. Multiple sclerosis is the leading non-traumatic cause of disability in young adults. Axonal damage is considered the pathologic substrate underlying clinical disability in MS but currently lacks a reliable imaging biomarker. Advanced diffusion MRI techniques with microstructural specificity for axon diameter and density offer the potential to improve the understanding of axonal damage in MS. The goal of the proposed research is to develop, validate and translate a new diffusion MRI method called Tract Caliber MRI to provide more direct and accurate measures of axonal damage in people with MS than existing MRI techniques. I will optimize the Tract Caliber technique to measure axon diameter and density within lesions and normal-appearing white matter in people with MS compared to healthy controls. The Tract Caliber measurements will then be validated against axon diameter and density measurements from histopathology performed on ex vivo brain tissue obtained at autopsy from MS patients. Once validated, Tract Caliber measurements of axon diameter and density in the corpus callosum and corticospinal tracts will be correlated with physical disability and cognitive dysfunction in MS patients compared to conventional MRI, magnetization transfer imaging, and diffusion tensor imaging in order to address the clinical utility of these different imaging techniques in tracking disease progression. This research proposal will enable me to achieve my short-term goal of becoming an independent investigator in translational neuroimaging. My ultimate goal is to lead an independently-funded research program in the development and clinical translation of novel imaging biomarkers for improving the care of patients with neurological diseases such as MS. To facilitate my progression to a position of independence, I have designed with my mentors a career development plan involving tailored didactic coursework, workshops, seminars, and hands-on training that will provide me with formal education in histopathological validation, disease pathogenesis, and clinical evaluation of patients with MS. The primary mentor for this project is Dr. Lawrence Wald, an expert in developing advanced diffusion MRI technology to solve specific biological and clinical problems. Dr. Howard Weiner will serve as the secondary mentor, lending his renowned expertise in MS. In addition, I will work with a team of collaborators/consultants from MGH (Dr. Bruce Fischl, Dr. Eric Klawiter), Boston University (Dr. Kathleen Rockland), and the Cleveland Clinic (Dr. Bruce Trapp), who will provide additional expertise and guidance as part of my scientific advisory committee. This research will be performed at the Martinos Center for Biomedical Imaging, a world-leading institution for translational neuroimaging and the study of the brain in health and disease. The project will greatly benefit from the unique resources of the Martinos Center, including the one-of-a-kind 3 Tesla Human Connectome MRI scanner equipped with ultra-high gradient strengths ideal for probing axonal microstructure. We will recruit patients with MS from the large patient population served by the MGH Multiple Sclerosis Clinic and Partners MS Center for the development and translational aims of this project and obtain fixed brain tissue samples from the MS tissue bank established at the Cleveland Clinic for the validation aim. This collaborative framework will help me foster relationships with leading experts in MS and will increase the impact and visibility of my research.

 描述（由应用程序提供）：在本应用程序中，我提出了一个技术开发，验证和翻译项目，旨在为多发性硬化症患者（MS）提供更好的轴突损伤成像标记。该奖项将提供受保护的研究时间和培训，以准备独立R01资金。多发性硬化症是年轻人的主要无创伤原因。轴突损伤被认为是MS中临床障碍的病理底物，但目前缺乏可靠的成像生物标志物。具有微观结构特异性的高级扩散MRI技术对轴突直径和密度，为提高对MS中轴突损伤的理解提供了潜力。拟议的研究的目的是开发，验证和翻译一种称为Tract Caliber MRI的新扩散MRI方法，以提供MS患者的轴突损伤的更直接和准确的测量，而不是现有MRI技术。与健康对照组相比，我将优化对病变内的轴突直径和密度和正常的白质的轴突直径和密度。然后，将针对MS患者在尸检时在尸检时对轴突的轴突直径和密度测量进行验证。一旦经过验证，与常规MRI，磁化转移成像和差异成像相比，MS患者的身体残疾和认知功能障碍与MS患者的身体残疾和认知功能障碍相关，以及差异张力张力成像以应对这些不同成像疾病的临床疾病进程。这项研究建议将使我能够实现成为转化神经影像学独立研究者的短期目标。我的最终目标是领导一项由新型成像生物标志物的开发和临床翻译中的独立研究计划，以改善MS等神经系统疾病患者的护理。为了促进我晋升为独立性的位置，我与导师一起设计了一项职业发展计划，涉及量身定制的教学课程，讲习班，半手和动手培训，这将为我提供有关MS患者的组织病理学验证，疾病发病机理和临床评估的正规教育。该项目的主要心理是劳伦斯·沃尔德（Lawrence Wald）博士，他是开发高级扩散MRI技术的专家，以解决特定的生物学和临床问题。霍华德·韦纳（Howard Weiner）博士将担任中学精神，并在MS中借用了他著名的专业知识。此外，我将与MGH（Bruce Fischl博士，Eric Klawiter博士，埃里克·克拉维特（Eric Klawiter）博士），波士顿大学（Kathleen Rockland博士）和克利夫兰诊所（Bruce Trapp博士）组成的合作者/顾问团队，他们将作为我的科学咨询委员会提供其他专业知识和指导。这项研究将在马提尼斯生物医学成像中心进行，这是一个世界领先的转化神经影像学机构，以及对健康和疾病中大脑的研究。该项目将大大受益于马提尼斯中心的独特资源，包括配备了超高梯度强度的独一无二的三个特斯拉人连接MRI扫描仪，非常适合探测轴突微观结构。我们将招募由MGH多发性硬化症诊所和MS MS的开发和转化目标中心服务的大量患者的患者，并从克利夫兰诊所建立的MS组织库中获得固定的脑组织样品，以验证目的。这个协作框架将有助于我与领先的关系建立关系 MS的专家将增加我的研究的影响和可见性。