Microstructure and connectivity modeling from the cortex to the spinal cord in Multiple Sclerosis

多发性硬化症从皮质到脊髓的微观结构和连接建模

• 批准号: 10429762
• 负责人: Kurt G Schilling
• 金额: $ 15.78万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10429762
• 关键词: Address; Affect; Anatomy; Axon; Biological Markers; Biophysical Process; Brain; Brain Mapping; Brain Stem; Brain imaging; Central Nervous System Diseases; Clinical; Clinical assessments; Complex; Corticospinal Tracts; Demyelinations; Deterioration; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Edema; Evaluation; Evolution; Fiber; Foundations; Goals; Health; Human; Image; Image Analysis; Impairment; Investigation; Lesion; Literature; Magnetic Resonance Imaging; Measures; Medical Imaging; Methods; Modeling; Morphologic artifacts; Motor Pathways; Multiple Sclerosis; Multiple Sclerosis Lesions; Neuraxis; Neurologic; Pathologic; Pathology; Pathway interactions; Prognosis; Radiology Specialty; Reproducibility; Research; Resolution; Role; Sensitivity and Specificity; Specificity; Spinal Cord; Spinal Cord Diseases; Spinal cord damage; Structure; Swelling; Techniques; Technology; Time; Tissue Model; Tissues; Water; axon injury; base; brain magnetic resonance imaging; brain pathway; burden of illness; cohesion; cohort; disability; image processing; improved; in vivo; indexing; magnetic resonance imaging biomarker; motor impairment; multiple sclerosis patient; nervous system disorder; spinal pathway; stem; tractography; white matter; white matter damage

Diffusion magnetic resonance imaging (MRI) enables the ability to probe both tissue microstructure and structural connectivity of the central nervous system. However, there are no validated methods to model and interrogate the pathways that connect the brain and spinal cord, which inhibits our ability to fully characterize and understand the complete damage that may occur in neurological disorders. For example, disease progression in patients with multiple sclerosis (MS) is known to stem from axonal damage in both the brain and spinal cord, yet, coordinated medical image analysis of both structures simultaneously has not been shown. Thus, the overall goal of the proposed research is to develop and optimize simultaneous tissue microstructural mapping of the brain and spinal cord for clinical assessment of MS using magnetic resonance imaging (MRI), specifically interrogating the microstructure and connectivity of motor pathways of the central nervous system. The critical challenges to this goal are (1) quantifying tissue microstructure of the brain and spinal cord in unison has not been performed, (2) clinical MRI lacks specificity for microstructural tissue integrity, and (3) there are few methods available that allow mapping of MS lesions and pathological abnormalities in relation to critical fiber pathways. To address this, in Aim 1 we will develop a cohesive acquisition and image processing pipeline, minimizing artifacts and maximizing reproducibility, in order to facilitate a unified analysis of the central nervous system. In Aim 2, we will utilize diffusion MRI modeling and fiber tractography to characterize tissue microstructure and connectivity from the cortex to the spinal cord. Modeling will enable quantification of highly specific pathophysiological indices of edema, axonal swelling, demyelination, and axonal loss, whereas tractography will facilitate feature localization to specific white matter pathways and along specific pathways. Finally, evaluate microstructure and connectivity of the motor pathways to interrogate pathology in MS, quantifying radiological biomarkers over space and time that may contribute to impairment in this disease. The overall impact of this proposal will be quantitative biomarkers for disease burden that may improve the value of imaging the brain and spinal cord together as it relates to understanding pathology in vivo.

扩散磁共振成像（MRI）使能够探测组织微观结构和 中枢神经系统的结构连通性。但是，没有验证的方法来建模和 询问连接大脑和脊髓的途径，这抑制了我们完全表征的能力 并了解神经系统疾病可能发生的完全损害。例如，疾病 已知多发性硬化症患者（MS）的进展源于大脑和大脑的轴突损伤 尚未显示两种结构的脊髓协调的医学图像分析。 因此，拟议的研究的总体目标是开发和优化同时的组织微观结构 使用磁共振成像（MRI）的大脑和脊髓映射MS的临床评估， 特别询问中枢神经系统电动通路的微观结构和连通性。 该目标的关键挑战是（1）量化大脑和脊髓的组织微观结构 尚未进行一致性，（2）临床MRI缺乏对微结构组织完整性的特异性，（3） 几乎没有可用的方法可以映射MS病变和病理异常 关键的纤维途径。为了解决这个问题，在AIM 1中，我们将开发一个有凝聚力的获取和图像处理 管道，最小化伪影并最大化可重复性，以促进对统一的分析 中枢神经系统。在AIM 2中，我们将利用扩散MRI建模和纤维拖拉术来表征 从皮质到脊髓的组织微观结构和连通性。建模将实现量化 水肿，轴突肿胀，脱髓鞘和轴突丧失的高度特异性病理生理指数，而 拖拉机将促进特征定位到特定的白质途径以及沿特定途径。 最后，评估电动机通路与MS中询问病理的微观结构和连通性， 在时间和时间上量化放射生物标志物，这可能导致这种疾病的损害。这 该提案的总体影响将是疾病负担的定量生物标志物，可以提高 将大脑和脊髓成像与理解体内病理学有关。