Brain MRI of Human Glaucoma

人类青光眼的脑部 MRI

• 批准号: 10488235
• 负责人: Timothy Q. Duong
• 金额: $ 40.74万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10488235
• 关键词: Affect; Age; American; Blindness; Brain; Cell Death; Clinical; Cross-Sectional Studies; Data; Disease; Disease Progression; Exhibits; Eye; Functional Magnetic Resonance Imaging; Fundus; Fundus photography; Glaucoma; Histologic; Human; Image; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Monitor; Nerve Degeneration; Nerve Fibers; Ophthalmic examination and evaluation; Ophthalmologist; Participant; Pathogenesis; Pathogenicity; Pathologic; Patients; Perimetry; Peripheral; Physiologic Intraocular Pressure; Play; Primary Open Angle Glaucoma; Reporting; Research Design; Resolution; Retinal Ganglion Cells; Role; Schedule; Severities; Severity of illness; Staging; Stimulus; Structural defect; Suspect Glaucomas; Testing; Thick; Vision; Visual Cortex; Visual Fields; Visual Pathways; Work; base; brain abnormalities; brain dysfunction; brain magnetic resonance imaging; brain pathway; central visual field; clinical risk; design; effective therapy; fiber cell; follow-up; gray matter; imaging scientist; improved; innovation; insight; longitudinal design; novel; pre-clinical; preservation; recruit; retinal nerve fiber layer; retinotopic; risk stratification; translational impact; treatment planning; treatment strategy; white matter

Abstract: Brain MRI of human glaucoma Primary open angle glaucoma (POAG) is a leading cause of blindness, affecting 4 million Americans. The disease starts with loss of peripheral vision followed by central vision. While elevated intraocular pressure is thought to be a critical pathogenic mechanism causing retinal ganglion cell death, many glaucoma patients continue to lose vision despite successful treatment to lower intraocular pressure. Here, we pursue a novel hypothesis that pathological changes to the brain also occur in glaucoma, contributing to disease pathogenesis and progression. This hypothesis is based on our preliminary fMRI data showing that mild to moderate POAG patients have functional remapping in the visual cortex. These preliminary fMRI data also show changes vary not only as a function of peripheral to central visual field but also as a function of disease severity. Further, these functional changes have structural correlates of gray- and white-matter degeneration in the brain visual pathways. More effective treatment for glaucoma may require comprehensive strategies that target both the eye and the brain. Our findings agree with prior histological evidence of concurrent neurodegeneration in the brain visual pathway in glaucoma. In fact, some studies even show that structural damage in the brain visual pathway precedes the loss of retinal ganglion cell fibers, suggesting neurodegeneration plays a role in this blinding disorder. A few prior fMRI studies, stimulating only the central visual field, have reported overall reduced stimulus-evoked activities in the visual cortex in glaucoma patients. However, it remains unknown to what extent the peripheral and central visual function in the visual cortex is altered in glaucoma and how this functional remapping relates to the progression of the disease. Based on our preliminary data, we hypothesize that glaucoma leads to functional remapping of the visual cortex as detected non-invasively by fMRI, and that more abnormal functional and structural neurodegeneration from MRI predicts faster progression of visual field loss in patients at the same clinical stage of glaucoma. The first aim of this study will determine functional and structural changes in the brain of glaucoma patients at different stages of severity in a cross-sectional design. The second aim will elucidate how changes in the brain can help to sub-stratify risk of clinical glaucoma progression in a longitudinal design. The translational impact will be increased by comparing MRI findings with clinical eye exams that include intraocular pressure, visual field perimetry, retinal nerve fiber layer thickness, and dilated fundus photography.

翻译后摘要：人类青光眼的脑MRI 原发性开角型青光眼（POAG）是致盲的主要原因，影响400万美国人。 这种疾病开始于周边视力的丧失，然后是中心视力。当眼内压升高 被认为是导致视网膜神经节细胞死亡的重要致病机制，许多青光眼患者 尽管成功治疗降低眼内压，但仍继续失去视力。在这里，我们追求一个小说 假设大脑的病理变化也发生在青光眼中，有助于疾病的发病机制 和进步。 这一假设是基于我们初步的fMRI数据显示，轻度至中度POAG患者 在视觉皮层中有功能性的重新映射。这些初步的功能磁共振成像数据还显示， 是周边视野到中央视野的函数，也是疾病严重程度的函数。此外，这些功能 这些变化与大脑视觉通路中的灰质和白质变性有结构相关性。更 青光眼的有效治疗可能需要针对眼睛和大脑的综合策略。 我们的研究结果与先前的组织学证据一致，即视觉系统中的脑神经退行性变 青光眼的治疗方法事实上，一些研究甚至表明，大脑视觉通路的结构性损伤 在视网膜神经节细胞纤维丧失之前，这表明神经变性在这种致盲中起作用。 disorder.一些先前的功能性磁共振成像研究，只刺激中央视野，已经报告了整体减少 青光眼患者视皮层的刺激诱发活动。然而，目前尚不清楚在多大程度上， 视皮层中的周边和中央视觉功能在青光眼中改变， 重新映射与疾病的进展有关。 根据我们的初步数据，我们假设青光眼导致视觉系统的功能重新映射， 功能磁共振成像检测非侵入性皮质，以及更多的异常功能和结构神经变性， 在相同临床阶段的青光眼患者中，来自MRI的预测视野丧失的进展更快。的 本研究的第一个目的是确定青光眼患者在不同时间的脑功能和结构变化。 横截面设计中的严重性阶段。第二个目标将阐明大脑的变化如何帮助 在纵向设计中对临床青光眼进展的风险进行子分层。翻译的影响将是 通过将MRI结果与临床眼科检查（包括眼内压、视野 视野检查、视网膜神经纤维层厚度和散瞳眼底照相。