Coherent light scattering for early detection of retinal disease

描述(由申请人提供)：这项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记物。最先进的技术是利用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，仅显示视网膜神经纤维层的厚度与青光眼的进展之间存在适度的相关性，在光感受器层的厚度与视网膜色素变性的进展之间也有类似的发现。这反映了这样一个事实，即单个视网膜层的厚度并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，角度分辨低相干干涉(a/LCI)是一种结合了OCT深度分辨率的光散射方法，可以获得深度分辨的食道上皮细胞形态测量，这使得可以在体内早期检测Barrett‘s食管病患者的异型增生。与其他非侵入性成像技术不同，a/LCI允许直接和特定地测量完整、未染色组织中的上皮细胞的核形态。我们已经证明，A/LCI可以检测到由于病理而引起的视网膜层细胞组织的变化。我们现在建议将a/LCI应用于眼部疾病的诊断，开发一种与扫描检眼镜兼容的a/LCI成像系统，以便对视网膜神经元的核形态进行深度分辨测量。在这里，我们将寻求建立准确的定量生物标志物，根据这些结构和组织变化来预测神经退行性眼部疾病的发生和发展。在这个项目中，(1)我们将实现一个原型a/LCI系统，以实现对视网膜的活体研究，以及(2)将该系统应用于对进行性视网膜变性小鼠模型的详细时间进程研究，以表征作为疾病进展的函数的光感受器结构的大小和组织的变化。在这项探索性研究成功完成后，将有理由继续开发一种应用于人类的临床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.