Magnetic Resonance Imaging of Glaucoma

描述（由申请人提供）：青光眼是世界上不可逆失明的主要原因，其特征在于视网膜神经节细胞（RGC）、视网膜神经纤维层和视神经的进行性变性。青光眼通常与眼内压（IOP）升高有关，并且由于IOP升高对眼睛中的血管施加压缩力，因此长期以来一直假设RGC损伤是由轻度但慢性的基础血流减少和/或血流失调引起的。对于许多患者来说，在检查中检测到青光眼或患者注意到视力丧失时，超过一半的RGC已经退化。最终的结果往往是失明。因此，能够检测深度分辨血流、氧合和刺激诱发的血流动力学变化以评估视网膜和视神经乳头中的血流减少和失调的非侵入性成像技术可以实现客观的早期检测、纵向疾病分期和治疗干预的监测。尽管基于光学的成像技术提供高空间分辨率，但是它们是深度有限的，这排除了视网膜、脉络膜和视神经血流的定量分辨率。本实验室 开创了多模态MRI的应用，以成像高分辨率的特定于椎板的解剖结构、血流、氧合和视网膜功能，而没有深度限制。在此，我们建议：i）开发多模式MRI方法，以显著提高对比度和空间分辨率（35 x35 x300 μ m），无MRI敏感性伪影，使用3D平衡稳态自由进动（bSSFP）数据采集方案，和ii）将该方法应用于已建立的遗传（DBA/2 J）中，小鼠青光眼模型，以确定MRI是否可以检测早期青光眼变化，并检查青光眼发病机制的可能性。我们假设：1）MRI可以提供高分辨率、深度分辨、无敏感性伪影的层特异性解剖学、血流和功能图像;以及2）青光眼的发病机制是由早期阶段的血流减少和/或血流失调介导的，导致缺血性缺氧导致RGC的最终损失，并且如果这是原因， 高氧治疗应该停止昏迷损害。

DESCRIPTION (provided by applicant): Glaucoma, a leading cause of irreversible blindness in the world, is characterized by progressive degeneration of the retinal ganglion cells (RGCs), the retinal nerve fiber layer, and the optic nerve. Glaucoma is often associated with elevated intraocular pressure (IOP), and because the increased IOP exerts a compressing force on the blood vessels in the eye, it has long been hypothesized that the RGC damage is caused by mild, but chronic, reduction of basal blood flow and/or blood-flow dysregulation. For many patients, by the time glaucoma is detected in examinations or patients notice vision loss, more than half of the RGCs have already degenerated. The eventual outcome is often blindness. Thus, non-invasive imaging technologies capable of detecting depth-resolved blood flow, oxygenation, and stimulus-evoked hemodynamic changes to evaluate blood flow reduction and dysregulation in the retina and the optic nerve head could enable objective early detection, longitudinal disease staging, and monitoring of therapeutic interventions. Although optically based imaging techniques provide high spatial resolution, they are depth limited which precludes quantitative resolution of retinal, choroidal, and optic nerve blood flow. Our laboratory pioneered the application of multimodal MRI to image high-resolution lamina-specific anatomy, blood flow, oxygenation, and function of the retina without depth limitation. Here we propose: i) to develop a multimodal MRI approach to markedly improve contrast and spatial resolution (35x35x300 �m) without MRI susceptibility artifact by using a 3D balanced Steady State Free Precession (bSSFP) data acquisition scheme, and ii) to apply this approach in an established genetic (DBA/2J) mouse glaucoma model to determine whether MRI can detect glaucomatous changes in early stage and examine a plausible mechanism of glaucoma pathogenesis. We hypothesize that: 1) MRI can provide high resolution, depth-resolved, laminar- specific anatomical, blood flow, and functional images free of susceptibility artifacts; and 2) the pathogenesis of glaucoma is mediated by reduced blood flow and/or blood-flow dysregulation in the early stage, resulting in eventual loss of RGCs by ischemic hypoxia, and, if this is the cause, hyperoxia treatment should halt glaucomatous damage.