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

项目摘要 本提案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改变， AD的指标，它只能在尸检或正电子发射断层扫描（PET） 成像，这可能非常昂贵。因此，最广泛使用的方法 诊断AD仍然是认知障碍的临床识别， 只有在排除了痴呆症的其他原因后才能提供可能的诊断。 由于视神经和视网膜是中枢神经系统的延伸， 研究试图将视网膜特征与疾病的发作联系起来。使用光学 相干断层扫描（OCT），已经观察到视网膜变薄与视网膜病变之间的相关性。 神经纤维层和AD，但这一特征也可以指示其他疾病。相反，我们建议 为了开发基于测量视网膜各层中的结构特征的诊断， 特别是识别可能与其他病理不同的AD的诊断度量。 为了实现这一目标，我们寻求发展角分辨低相干干涉术（a/LCI） 用于视网膜层结构特征的临床测量。a/LCI是一种光散射方法 它结合了光散射的亚细胞灵敏度和OCT的深度分辨率， 已经显示使用体内深度检测食管和宫颈中的癌前细胞 核形态的分辨测量。而不是成像的细胞结构， 视网膜直接，我们建议使用/LCI来测量微米级结构 视网膜层的特征。初步数据显示， 这些结构的组织与鼠模型中AD的存在相关。以下 具体目标是：1。实施集成的a/LCI和OCT系统，用于体内研究 人类的视网膜2.描述患有a/LCI和OCT的AD患者的视网膜特征。 将确认动物模型的测量结果，并为建立生物标志物提供数据 AD在人类3.使用形态学进行生物标志物开发的数据分析 描述符和机器学习。4.在AD患者中进行体内前瞻性研究，以验证 结构变化的生物标志物作为疾病的预测。在完成这个项目后，我们将 已经显示出可行性，并为未来发展a/LCI和 用于AD临床筛查的OCT系统。

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.