Layer-specific imaging of retinal degeneration

描述（由申请人提供）：视网膜色素变性（RP）是一组以进行性光感受器变性为特征的遗传性疾病，影响全球150万人。位于视网膜两侧的血管（脉络膜和视网膜）层和其他（双极和神经节）细胞层也受到影响。目前RP的临床评估严重依赖于目视检查。能够检测层特异性细胞和血管变化的非侵入性成像技术将能够实现客观的早期检测、纵向疾病分期、治疗干预的监测以及对潜在病理生理学的更好理解。基于光学的视网膜成像技术可能受到介质不透明度（即，白内障和玻璃体破裂），这妨碍了视网膜深层和血管的可视化。相比之下，磁共振成像（MRI）提供解剖学，生理学和功能的非侵入性图像，而没有深度限制。然而，实现视网膜MRI的足够空间分辨率仍然具有挑战性。在这项提案中，我们将开发新的解剖学，生理学和功能性MRI，以解决60x60x500 5m的视网膜各层，并通过纵向研究皇家外科学院（RCS）大鼠视网膜（一种已建立的人类RP模型）的进行性，层特异性视网膜变性来大力测试这种能力。公共卫生相关性：该提案概述了新型MRI方法的开发、交叉验证和应用，以非常高的空间分辨率解决视网膜的结构、生理和功能层特异性。它对该领域具有很强的临床意义和潜在影响，因为它可以提供1）视网膜变性的早期标志物和用于监测治疗干预，以及2）对视网膜和脉络膜血流和氧合如何调节以及视网膜变性如何影响它们所维持的两个血管和神经组织的有力见解。来自这些动物研究的数据应该推进这些研究领域，为视网膜研究开辟新的途径，并为未来的人类研究奠定基础。

DESCRIPTION (provided by applicant): Retinitis pigmentosa (RP) is a group of inherited diseases marked by progressive photoreceptor degeneration, affecting 1.5 million people worldwide. The vascular (choroidal and retinal) layers located on either side of the retina and other (bipolar and ganglion) cell layers are also affected. Current clinical assessment of RP relies heavily on visual testing. Non-invasive imaging technologies capable of detecting layer-specific cellular and vascular changes would enable objective early detection, longitudinal disease staging, monitoring of therapeutic intervention, and improved understanding of the underlying pathophysiology. Optical-based retinal imaging techniques can be limited by media opacity (i.e., cataracts and vitreous hemorrhages) which precludes visualization of deep retinal layers and vessels. In contrast, magnetic resonance imaging (MRI) provides non-invasive images of anatomy, physiology and function without depth limitation. Achieving sufficient spatial resolution for retinal MRI, however, remains challenging. In this proposal, we will develop novel anatomical, physiologic and functional MRI to resolve various layers of the retina at 60x60x500 5m, and vigorously test this capability by longitudinally investigating progressive, layer-specific retinal degeneration in the Royal-College-of-Surgeon (RCS) rat retinas, an established model of human RP. PUBLIC HEALTH RELEVANCE: This proposal outlines the development, cross-validation and application of novel MRI approaches to resolve structural, physiological and functional laminar specificity of the retina at very high spatial resolution. It has strong clinical significance and potential impact to the field in that it can provide 1) an early marker of retinal degeneration and for monitoring therapeutic intervention and 2) powerful insights into how retinal and choroidal blood flow and oxygenation are regulated and how retinal degeneration affects the two vasculatures and the neural tissues they subserve. Data from these animal studies should advance these areas of research, open up new avenues for retinal research, and lay the foundation for future human studies.