Brain MRI of Human Glaucoma

人类青光眼的脑部 MRI

• 批准号: 10313017
• 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 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10313017
• 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; Structure; Suspect Glaucomas; Testing; Thick; Vision; Visual Cortex; Visual Fields; Visual Pathways; Work; base; brain abnormalities; 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.

摘要：人类青光眼的脑部 MRI 原发性开角型青光眼 (POAG) 是导致失明的主要原因，影响着 400 万美国人。 该疾病始于周边视力丧失，随后是中心视力丧失。眼压升高的同时 被认为是导致视网膜神经节细胞死亡的关键致病机制，许多青光眼患者 尽管成功地进行了降低眼压的治疗，但视力仍继续下降。在这里，我们追求一部小说 假设青光眼也会发生大脑的病理变化，从而导致疾病的发病机制 和进展。 这一假设基于我们的初步功能磁共振成像数据，显示轻度至中度 POAG 患者 视觉皮层有功能重新映射。这些初步的功能磁共振成像数据还表明变化不仅在于 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灰质和白质变性具有结构相关性。更多的 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大脑视觉并发神经退行性变的组织学证据一致 青光眼的途径。事实上，一些研究甚至表明大脑视觉通路的结构损伤 先于视网膜神经节细胞纤维的损失，表明神经退行性变在这种致盲中发挥了作用 紊乱。一些先前的功能磁共振成像研究仅刺激中央视野，报告称总体减少 青光眼患者视觉皮层的刺激诱发活动。但具体到什么程度仍不得而知 青光眼患者视觉皮层的周边和中央视觉功能发生改变，以及这种功能如何改变 重新映射与疾病的进展有关。 根据我们的初步数据，我们假设青光眼会导致视觉功能重新映射 通过功能磁共振成像（fMRI）非侵入性检测到皮层，并且发现更多异常的功能性和结构性神经退行性变 MRI 预测青光眼同一临床阶段患者的视野丧失进展更快。这 这项研究的首要目标是确定青光眼患者在不同时期大脑的功能和结构变化。 横截面设计中的严重程度阶段。第二个目标将阐明大脑的变化如何提供帮助 在纵向设计中对临床青光眼进展的风险进行分层。转化影响将是 通过将 MRI 结果与临床眼科检查（包括眼压、视野）进行比较来增加 视野检查、视网膜神经纤维层厚度和散瞳眼底照相。