Mesoscopic Biomarkers of Neurodegeneration with Diffusion MRI

弥散 MRI 神经退行性变的细观生物标志物

基本信息

批准号：
8744985
负责人：
Els Fieremans
金额：
$ 37.08万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8744985
关键词：
Acute Affect Alzheimer&apos s Disease American Amyotrophic Lateral Sclerosis Architecture Biological Markers Brain Brain region Central Nervous System Diseases Chronic Clinic Clinical Clinical Data Complex Computer software Corpus Callosum Corticospinal Tracts Demyelinations Development Diagnostic Diffusion Diffusion Magnetic Resonance Imaging Disease Disease Progression Fiber Future Geometry Gliosis Goals Grant Human Huntington Disease Image Individual Inflammation Injury Institution Life MRI Scans Magnetic Resonance Imaging Maps Measures Metric Modeling Molecular Monitor Multiple Sclerosis Myelin Nerve Degeneration Nervous System Trauma Neurodegenerative Disorders Parkinson Disease Pathologic Processes Pathology Patients Physics Physiological Process Protocols documentation Protons Public Health Radial Relative (related person)Resolution Retrospective Studies Series Severities Severity of illness Signal Transduction Specificity Testing Therapeutic Time Tissues Translating Translations Traumatic Brain Injury Validation Water Weight analytical method axonal degeneration base brain tissue cost density diagnostic accuracy disability health economics imaging modality improved in vivo innovation leukodystrophy millimeter molecular scale nanometer nervous system disorder neurological pathology normal aging novel public health relevance response role model soft tissue theories treatment response water diffusion white matter white matter damage white matter injury

项目摘要

DESCRIPTION (provided by applicant): Diseases of the central nervous system (CNS) are a significant public health and economic problem, affecting nearly one in three Americans at some point in life, with a cost exceeding $500 billion per year. Pathologically, the axonal integrity in the brain white matter is compromised in most human neurological diseases or injuries, including multiple sclerosis, leukodystrophy, traumatic brain injury, as well as in normal aging and neurodegenerative diseases such as Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Alzheimer's disease. Neurodegeneration occurs via a number of distinct processes, such as acute axonal injury, demyelination, inflammation, chronic axonal degeneration or axonal loss, and gliosis. Quantifying their degree, and distinguishing between these different underlying degenerative processes is particularly vital for adequate assessment of CNS disease progression and treatment, but currently not available. The main objective of this proposal is the development, validation and clinical translation of MesoMRI, a newly proposed framework that yields high specificity of diffusion MRI metrics to different degenerative processes by identifying how structural changes at the mesoscopic scale manifest themselves in the diffusion-weighted signal. The mesoscopic scale is the scale of cellular tissue architecture, intermediate between the molecular scale and the macroscopic MRI resolution. Our overall hypothesis is that our novel mesoscopic biomarkers of brain tissue integrity will be specific to different aspects of neurodegeneration in vivo, including demyelination and axonal loss. The development of the mesoscopic MRI framework involves qualitative understanding and quantitative modeling of the role of axonal geometry at the micrometer scale, and the response of water diffusion metrics to demyelination, axonal loss, injury, and other pathological changes. This involves bringing advanced analytical methods borrowed from modern transport theory and statistical physics into the context of diffusion MRI. In particular, we will first deveop and validate our white matter tract integrity metrics and the relation between them and the degree of demyelination and axonal loss in a single white matter fiber bundle. Subsequently, we will extend the mesoscopic modeling of a single fiber bundle onto the whole white matter, including regions of multiple fiber directions and crossings. This extension involves the development of MesoFT, a novel mesoscopic modeling and fiber tracking paradigm, able for the first time to produce self-consistent maps of both local mesoscopic parameters of fibers and their macroscopic connectivity maps. The potential of our technical developments for clinical translation will be evaluated by applying MesoFT to retrospectively acquired clinical cases of Alzheimer's disease and multiple sclerosis. Based on adequate interpretation of standard clinically feasible diffusion MRI metrics, our framework's translation into clinic will be straightforward, and will enable the quantitative assessment of disease progression and quality of treatment in neurological diseases.

描述（由申请人提供）：中枢神经系统 (CNS) 疾病是一个重大的公共卫生和经济问题，在生命的某个阶段影响近三分之一的美国人，每年造成的费用超过 5000 亿美元。病理学上，轴突完整性大多数人类神经系统疾病或损伤（包括多发性硬化症、脑白质营养不良、创伤性脑损伤）以及正常衰老和神经退行性疾病（如帕金森病、亨廷顿病、肌萎缩侧索硬化症和阿尔茨海默病）中，大脑白质都会受到损害。神经变性通过许多不同的过程发生，例如急性轴突损伤、脱髓鞘、炎症、慢性轴突变性或轴突损失以及神经胶质增生。量化其程度并区分这些不同的潜在退行性过程对于充分评估中枢神经系统疾病进展和治疗尤其重要，但目前尚不可行。该提案的主要目标是 MesoMRI 的开发、验证和临床转化，MesoMRI 是一种新提出的框架，通过识别介观尺度的结构变化如何在扩散加权信号中表现出来，产生针对不同退行性过程的扩散 MRI 指标的高特异性。介观尺度是细胞组织结构的尺度，介于分子尺度和宏观 MRI 分辨率之间。我们的总体假设是，我们的脑组织完整性的新型介观生物标志物将特定于体内神经变性的不同方面，包括脱髓鞘和轴突损失。细观 MRI 框架的开发涉及对微米尺度轴突几何形状的作用的定性理解和定量建模，以及水扩散指标对脱髓鞘、轴突损失、损伤和其他病理变化的响应。这涉及将从现代传输理论和统计物理学借用的先进分析方法引入扩散 MRI 的背景中。特别是，我们将首先开发和验证我们的白质束完整性指标以及它们与单个白质纤维束中脱髓鞘和轴突损失程度之间的关系。随后，我们将把单个纤维束的介观模型扩展到整个白质，包括多个纤维方向和交叉的区域。这一扩展涉及 MesoFT 的开发，这是一种新颖的介观建模和光纤跟踪范例，首次能够生成光纤局部介观参数及其宏观连接图的自洽图。我们将通过将 MesoFT 应用于回顾性获得的阿尔茨海默病和多发性硬化症的临床病例来评估我们临床转化技术开发的潜力。基于对标准临床可行的扩散 MRI 指标的充分解释，我们的框架将很容易转化为临床，并将能够对神经系统疾病的疾病进展和治疗质量进行定量评估。