Coherent light scattering for early detection of retinal disease

描述（由申请人提供）：本提案的总体目标是开发一种新的体内光学成像系统，该系统将量化视网膜退行性疾病的结构生物标志物。最先进的技术是通过光谱域光学相干断层扫描（SDOCT）测量视网膜层的厚度。然而，尽管SDOCT可以分辨组织层，但它缺乏测量细胞特征的分辨率。在最近的SDOCT研究中，视网膜神经纤维层厚度与青光眼的进展之间只有适度的相关性，而感光层厚度与视网膜色素变性的进展之间也有类似的发现。这反映了一个事实，即单个视网膜层的厚度不一定与其组成细胞的健康或解剖状况相关。我们已经证明，角分辨低相干干涉法（a/LCI），一种结合了OCT深度分辨率的光散射方法，可以获得食管上皮细胞的深度分辨形态学测量，这可以在体内早期检测Barrett食管患者的发育不良，与其他非侵入性成像技术不同，a/LCI可以直接和特定地测量完整未染色组织内上皮细胞的核形态。我们已经证明，a/LCI可以检测到病理导致的视网膜层细胞组织的变化。我们现在建议通过开发与扫描检眼镜兼容的a/LCI成像系统，将a/LCI应用于眼部疾病的诊断，以便对视网膜神经元的核形态进行深度分辨率测量。在这里，我们将寻求制定准确的定量生物标志物，以预测基于这些结构和组织变化的神经退行性眼部病变的发生和进展。在这个项目中，(1)我们将实现一个原型a/LCI系统，以实现视网膜的体内研究；(2)将该系统应用于进行性视网膜变性的小鼠模型的详细时间过程研究，以表征光感受器结构的大小和组织的变化作为疾病进展的功能。在成功完成这项探索性研究后，将有理由继续开发用于人类的临床a/LCI设备。

DESCRIPTION (provided by applicant): The overall objective of this proposal is to develop a novel in vivo optical imaging system that will quantify structural biomarkers of retinal degenerative diseases. The state-of-the-art technology is measurement of the thickness of retina layers by spectral domain optical coherence tomography (SDOCT). However, while SDOCT can resolve histological layers, it lacks the resolution to measure cellular features. In recent SDOCT studies, only a modest correlation between the thickness of the retinal nerve fiber layer and the progression of glaucoma has been shown, with similar findings seen between the thickness of the photoreceptor layer and progression of retinitis pigmentosa. This reflects the fact that thickness of an individual retina layer does not necessarily correlate with the healt or anatomical condition of its constituent cells. We have shown that angle-resolved low coherence interferometry (a/LCI), a light scattering method that incorporates the depth resolution of OCT, can acquire depth-resolved morphological measurements of esophageal epithelial cells, which allows in vivo early detection of dysplasia in Barrett's Esophagus patients Unlike other non-invasive imaging techniques, a/LCI allows direct and specific measurements of the nuclear morphology of epithelial cells within intact, unstained tissues. We have shown that a/LCI can detect changes in organization of cells in the retinal layer due to pathology. We now propose to apply a/LCI to the diagnosis of ocular diseases by developing an a/LCI imaging system that is compatible with a scanning ophthalmoscope in order to execute depth-resolved measurements of the nuclear morphology of retinal neurons. Here we will seek to formulate accurate quantitative biomarkers that predict the onset and progression of neurodegenerative ocular pathologies based on these structural and organizational changes. In this project, (1) we will implement a prototype a/LCI system to enable in vivo studies of the retina and (2) apply the system to a detailed time course study of a murine model of progressive retinal degeneration to characterize the changes in both size and organization of photoreceptor structures as a function of disease progression. Upon successful completion of this exploratory research study, there will be justification to pursue development of a clinical a/LCI device for application to humans.