Retinal Light Scattering Measurements as a Clinical Biomarker of Alzheimer's Disease

项目摘要 这项建议的总体目标是证明一种新方法的临床可行性。 虽然脑组织中淀粉样斑块的沉积是最明显的病理 AD的标志，只有在尸检或正电子发射断层扫描(PET)中才能检测到 成像，这可能是令人望而却步的昂贵。因此，最广泛使用的方法是 阿尔茨海默病的诊断仍然是临床认知障碍的一种主观认识 只有在消除了痴呆的其他原因后才能提供可能的诊断的评估。 因为视神经和视网膜是中枢神经系统的延伸， 寻求的调查试图将视网膜特征与疾病的发病联系起来。使用光纤 相干断层扫描(OCT)，已经观察到视网膜变薄与 神经纤维层和阿尔茨海默病，但这一特征也可以提示其他疾病。相反，我们建议 为了开发基于测量视网膜不同层的结构特征的诊断， 具体地说，以确定潜在有别于其他病理的AD的诊断指标。 为了满足这一目标，我们寻求发展角度分辨低相干度测量(a/lci)。 用于临床测量视网膜层的结构特征。A/LCI是一种光散射方法 这结合了光散射的亚细胞敏感度和OCT的深度分辨率。它 已被证明可以使用活体深度检测食道和宫颈中的癌前细胞 解决了对核形态的测量。而不是成像细胞结构 我们建议使用a/lci来测量微米级的结构。 视网膜各层的特征。初步数据显示，A/LCI测量的 这些结构的组织与小鼠模型中AD的存在相关。以下是 具体目标是：1.建立A/LCI和OCT一体化的体内研究系统 人类的视网膜。2.用a/LCI和OCT研究AD患者的视网膜特征。本研究 将确认动物模型的测量结果，并为建立生物标记物提供数据 阿尔茨海默病在人类中的作用。3.利用形态学进行生物标记物开发的数据分析 描述符和机器学习。4.对AD患者进行体内前瞻性研究以验证 作为疾病预测的结构变化的生物标记物。在这个项目完成后，我们将 已经证明了A/LCI合并的可行性，并为未来的发展提供了理由 OCT系统用于AD的临床筛查。

Project Summary The overall objective of this proposal is to demonstrate the clinical feasibility of a novel method Although deposition of amyloid plaques in brain tissue is the clearest pathological indicator of AD, it can only be detected during autopsy or positron emission tomography (PET) imaging, which can be prohibitively expensive. As a result, the most widely used approach for diagnosing AD continues to be the clinical recognition of cognitive impairment, a subjective evaluation which only provides probable diagnosis when other causes of dementia are eliminated. Because the optic nerve and retina are extensions of the central nervous system, several investigations to seek have sought to link retinal features with onset of the disease. Using optical coherence tomography (OCT), a correlation has been observed between thinning of the retinal nerve fiber layer and AD but this feature can also indicate other diseases. Instead, we propose to develop a diagnostic based on measuring structural features in the various layers of the retina, specifically to identify a diagnostic metric of AD that is potentially distinct from other pathologies. To meet this objective, we seek to develop angle-resolved low coherence interferometry (a/LCI) for clinical measurement of structural features of retinal layers. a/LCI is a light scattering method that combines the sub-cellular sensitivity of light scattering with the depth resolution of OCT. It has been shown to detect precancerous cells in esophagus and cervix using in vivo depth resolved measurements of nuclear morphology. Rather than imaging the cellular structure of the retina directly, we instead propose to use a/LCI to measure the micron-scale structural characteristics of retinal layers. Preliminary data shows that a/LCI measurements of the organization of these structures correlates with presence of AD in a murine model. The following Specific Aims are proposed: 1. Implement integrated a/LCI & OCT system for in vivo studies of the human retina. 2. Characterize retinal features in AD patients with a/LCI & OCT. This study will confirm measurements from the animal model and provide data for establishing biomarkers of AD in humans. 3. Conduct data analysis for biomarker development using morphological descriptors and machine learning. 4. Perform in vivo prospective studies in AD patients to validate biomarkers of structural changes as predictive of disease. Upon completion of this project, we will have shown feasibility and provided justification for future development of a combined a/LCI & OCT system for clinical screening for AD.