Imaging the Pathophysiology of AMN in Mice and Humans

小鼠和人类 AMN 病理生理学成像

基本信息

批准号：
7869234
负责人：
FLORIAN S EICHLER
金额：
$ 17.56万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-06-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7869234
关键词：
Adrenoleukodystrophy Adrenomyeloneuropathy Affect Alzheimer&apos s Disease Amyotrophic Lateral Sclerosis Animal Model Animals Anisotropy Area Arts Award Biochemical Biological Biological Markers Brain Carrier Proteins Cells Cerebrum Cessation of life Choline Clinical Degenerative Disorder Demyelinations Development Diffusion Diffusion Magnetic Resonance Imaging Disease Disease Progression Environment Exposure to Fiber Functional disorder Future Genetic Genotype Goals Human Image Imaging Techniques Immunologics In Vitro Inflammatory Inflammatory Response Interdisciplinary Study Investigation Knowledge Lead Lesion Lipid Chemistry Lipids Magic Magnetic Resonance Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Maps Measurement Measures Membrane Mentors Metabolic Mus Mutation Myelin Myelin Sheath NMR Spectroscopy Natural History Nervous system structure Neurodegenerative Disorders Neurologic Dysfunctions Neurosciences Parkinson Disease Pathology Patients Pattern Peroxisomal Disorders Phenotype Physics Protons Research Research Personnel Research Project Grants Research Training Science Side Structure Study models Techniques Therapeutic Training Training Programs Variant Very Long Chain Fatty Acid brain metabolism career development density experience in vivo insight lipid metabolism magnetic resonance spectroscopic imaging morphometry mouse model novel therapeutics prospective spectroscopic imaging tool translational study white matter

项目摘要

DESCRIPTION (provided by applicant): The proposed interdisciplinary study allows the candidate to further develop his knowledge of MR physics and expertise in imaging studies of adrenomyeloneuropathy (AMN), a form of adrenoleukodystrophy (ALD), while providing rigorous exposure to the clinical and biological side of this research. The goal is to increase the candidate's expertise in multiple areas necessary to his proposed research project and future career development. These areas include genetics of peroxisomal disorders, lipid metabolism, and spatial aspects of nuclear magnetic resonance spectroscopy. The proposal builds nicely on the candidate's prior experience with Dr. Moser at Johns Hopkins and extends his studies to the animal model. The candidate is in a world-renown environment for both MR imaging and neuroscience. This Award will provide the guidance and tools necessary for him to become a successful, independent researcher. The 5 year research training program consists of 1) coursework and mentoring relationships on the science of high-field magnetic resonance that the candidate is currently lacking, 2) a 2 year rigorous training in animal imaging, and 3) collaborative translational studies with experts in the field of lipid metabolism and peroxisomal disorders. The research portion of this application will allow him to examine the histopathological and biochemical correlate of advanced MR techniques in the mouse model of ALD. This has never been done before and likely to reveal insight into the fundamental dynamics of demyelination. Further, the proposal encompasses application of novel therapeutics to normalize lipid metabolism and stabilize myelin membrane integrity. Hypotheses include: 1) in the animal model of ALD, measures of diffusion tensor imaging can assess the density of white matter tracts in the mouse and measures of single voxel proton MR spectroscopy reflect changes in lipid composition of the brain, and 2) in ALD patients, metabolic changes seen on proton MR spectroscopic imaging herald lesion development on conventional MRI. Our results will yield a noninvasive means of gauging the effects of experimental and therapeutic manipulations of lipid chemistry upon specific neuroanatomic structures. Ultimately, insights gained in these studies of ALD/AMN may prove beneficial to other neurodegenerative diseases, such as amyotrophic lateral sclerosis or Parkinson's and Alzheimer's diseases.

描述（由申请人提供）：拟议的跨学科研究允许候选人进一步发展他对肾上腺瘤肌病（AMN）成像研究中MR物理学和专业知识的了解，这是一种肾上腺素肌营养不良（ALD）的一种形式，同时为这项研究的临床和生物学方面提供了严格的暴露。目的是提高候选人在其拟议的研究项目和未来职业发展所需的多个领域的专业知识。这些领域包括过氧化物酶体疾病，脂质代谢以及核磁共振光谱的空间方面的遗传学。该提案很好地基于候选人在约翰·霍普金斯（Johns Hopkins）的摩泽尔博士（Moser）的先前经验，并将其研究扩展到动物模型。该候选人处于MR成像和神经科学的世界享有盛誉的环境中。该奖项将为他成为一名成功的独立研究人员提供必要的指导和工具。为期5年的研究培训计划包括1）候选人目前缺乏的高场磁共振科学的课程和指导关系，2）2）在动物成像方面进行了2年的严格培训，以及3）与脂质代谢和过氧化物症领域专家的协作转化研究。本应用的研究部分将使他能够检查ALD小鼠模型中高级MR技术的组织病理学和生化相关性。这从未有过，并且很可能揭示了对脱髓鞘基本动态的见解。此外，该提案涵盖了新型疗法的应用，以使脂质代谢正常化并稳定髓鞘膜完整性。 Hypotheses include: 1) in the animal model of ALD, measures of diffusion tensor imaging can assess the density of white matter tracts in the mouse and measures of single voxel proton MR spectroscopy reflect changes in lipid composition of the brain, and 2) in ALD patients, metabolic changes seen on proton MR spectroscopic imaging herald lesion development on conventional MRI.我们的结果将产生一种无创的手段，以衡量脂质化学对特定神经解剖结构的实验和治疗操作的影响。最终，在这些ALD/AMN的研究中获得的见解可能对其他神经退行性疾病有益，例如肌萎缩性侧索硬化症或帕金森氏症和阿尔茨海默氏病。