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

扩散磁共振成像(MRI)能够探测组织微结构和 中枢神经系统的结构性连接。然而，还没有经过验证的方法来建模和 询问连接大脑和脊髓的路径，这抑制了我们充分描述 并了解在神经紊乱中可能发生的完全损害。例如，疾病 多发性硬化症(MS)患者的进展已知源于大脑和大脑中的轴突损伤 然而，同时对两个结构进行协调的医学图像分析还没有显示出来。 因此，拟议研究的总体目标是开发和优化同步的组织微结构 使用磁共振成像(MRI)对多发性硬化症进行临床评估的脑和脊髓标测， 特别是询问中枢神经系统运动通路的微观结构和连通性。 实现这一目标的关键挑战是(1)对大脑和脊髓的组织微结构进行量化 (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与以下相关的MS损害和病理异常 关键的纤维通路。为了解决这个问题，在目标1中，我们将开发一个内聚式采集和图像处理 流水线，最大限度地减少伪影和最大限度地提高再现性，以便促进对 中枢神经系统。在目标2中，我们将利用弥散磁共振建模和纤维束成像来表征 组织微结构和从皮质到脊髓的连通性。建模将使量化 高度特异的水肿、轴突肿胀、脱髓鞘和轴突丢失的病理生理指标，而 纤维束造影术将有助于将特征定位到特定的白质通路和沿着特定的通路。 最后，评估运动通路的微观结构和连通性，以询问MS的病理， 在空间和时间上量化可能导致这种疾病损害的放射生物标记物。这个 这项提案的总体影响将是疾病负担的量化生物标记物，可能会提高 对大脑和脊髓进行成像，因为它与了解活体病理有关。

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.