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

扩散磁共振成像（MRI）能够探测组织微观结构和 中枢神经系统的结构连接。然而，没有经过验证的方法来建模， 询问连接大脑和脊髓的通路，这抑制了我们充分描述 并了解神经系统疾病可能造成的全面损害。例如疾病 已知多发性硬化症（MS）患者的进展源于脑和脊髓中的轴突损伤， 然而，还没有显示同时对两种结构进行协调的医学图像分析。 因此，所提出的研究的总体目标是开发和优化同时组织微观结构 使用磁共振成像（MRI）对脑和脊髓进行测绘以用于MS的临床评估， 特别是询问中枢神经系统运动通路的微观结构和连接性。 这一目标的关键挑战是（1）量化脑和脊髓的组织微结构， 尚未进行协调，（2）临床MRI缺乏对微结构组织完整性的特异性，以及（3） 很少有方法可以用于绘制MS病变和与MS相关的病理异常， 关键的纤维通路。为了解决这个问题，在目标1中，我们将开发一个有凝聚力的采集和图像处理 管道，最大限度地减少人为因素和最大限度地提高再现性，以促进统一分析 中枢神经系统在目标2中，我们将利用弥散MRI建模和纤维束成像来表征 从皮质到脊髓的组织微观结构和连接性。建模将使量化 高度特异性的水肿、轴突肿胀、脱髓鞘和轴突丢失的病理生理学指标，而 纤维束成像将促进特征定位到特定的白色物质通路和沿沿着特定通路。 最后，评估运动通路的微观结构和连通性，以询问MS的病理学， 在空间和时间上定量放射学生物标志物，可能有助于这种疾病的损害。的 该提案的总体影响将是疾病负担的定量生物标志物， 将脑和脊髓一起成像，因为它涉及了解体内病理学。

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.