Multi-Modality, Quantitative MRI to Assess the Human Optic Nerve in vivo

描述（由申请人提供）：视神经炎，以特发性，突发性视神经炎症（ON）为特征，是MS最常见的症状，估计50%的MS患者有视神经炎病史，通常随着时间的推移而消退，并且没有有效的治疗方法。然而，它的存在可能是MS早期阶段的标志，即使临床症状解决，也可能代表破坏性的轴突和髓鞘病理。我们的第一个假设是，使用对轴突和髓鞘完整性敏感的MRI方法评估视神经可以提供ms患者ON显微组织变化的定量信息。我们的第二个假设是，这些指标可能与视网膜神经纤维层（光学相干断层扫描[OCT]）厚度和视觉功能障碍（低对比视力）的测量有关。我们的总体目标是设计并验证一套多模态、髓鞘和轴突敏感的MR指标，用于临床常规应用，以研究有视神经炎病史和无视神经炎病史的MS患者的显性和隐性ON损伤。为了实现我们的目标，我们制定了以下具体目标。目的1：发展扩散张量成像（DTI）和磁化转移（MT）成像的ON，其结构的大小，持续运动和接近上颌窦（增加磁化率的工件）阻碍了DTI和MT方法。将在健康对照中评估所得DTI和MT指标的可重复性。目的2：评估DTI和MT方案检测有视神经炎病史的MS患者病理的能力。将患者数据与AIM 1中获得的健康志愿者数据进行比较，并评估ON损伤的敏感性和特异性。目的3：将有或没有视神经炎病史的MS患者的神经网络的MT和dti衍生指标与1)OCT确定的视网膜神经纤维层厚度和2)临床评估的低对比度视力联系起来。

DESCRIPTION (provided by applicant): Optic Neuritis, marked by idiopathic, sudden inflammation of the optic nerve (ON), is the most commonly presenting symptom of MS. An estimated 50% of MS patients have a history of optic neuritis, which often resolves with time, and there are no effective treatments. However, its mere presence can be a signature of the early stages of MS, which, even with resolved clinical symptoms, could represent devastating axonal and myelin pathology. Our first hypothesis is that assessment of the optic nerve using MRI methods sensitive to axonal and myelin integrity can provide quantitative information about microscopic tissue changes in the ON of patients with MS. Our second hypothesis is that these metrics can be related to measures of the retinal nerve fiber layer (optical coherence tomography [OCT]) thickness, and visual dysfunction (low contrast visual acuity). Our overall goal is to devise and validate a multi-modality, myelin and axonal sensitive set of MR metrics for routine application in the clinic to study overt and silent ON damage in MS patients with and without history of optic neuritis. To accomplish our goal, we have set the following specific Aims. Aim 1: To develop Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) imaging for the ON, a structure whose size, constant motion and proximity to the maxillary sinuses (increased magnetic susceptibility artifacts) has hampered DTI and MT methods. The reproducibility of the derived DTI and MT metrics will be assessed in healthy controls. Aim 2: To assess the ability of the DTI and MT schemes to detect pathology in patients with MS who have history of optic neuritis. Patient data will be compared with the healthy volunteer data obtained in AIM 1, and the sensitivity and specificity for ON damage will be assessed. Aim 3: To relate MT and DTI-derived metrics of the ON in MS patents with and without history of optic neuritis to 1) retinal nerve fiber layer thickness as determined by OCT and 2) low-contrast visual acuity assessed in the clinic. RELEVANCE: It is known that 17-20% of patients who present with optic neuritis eventually develop MS. The relevance is that quantitative diffusion and magnetization transfer MRI evaluation of the microstructure of the optic nerve (ON) in MS with or without history of optic neuritis may provide an earlier biomarker for MS and the evolution of MS. These methods should be applicable to other ON pathologies, and other difficult CNS tissues outside the brain.