Investigating changes in cerebral blood flow response to local neural stimulation in Alzheimer disease retina as a potential mechanism for early diagnosis

阿尔茨海默病（AD）是一种脑部疾病，是美国第六大死因。如果阿尔茨海默病发展到认知能力下降，就不能减缓或治愈。早期发现有利于及时干预，避免脑细胞损失，提高患者生活质量。该项目的主要目标是通过一套相对简单的眼部成像程序，建立一种可行且具有成本效益的早期检测AD的策略。将开发新的光学技术来测量与AD相关的眼睛和脑血流的变化。机器学习工具将被用来预测疾病的发展轨迹。此外，该项目将为工程专业学生提供培训机会，让他们了解AD，并运用他们的工程技能，为抗击这一毁灭性疾病的集体努力做出贡献。阿尔茨海默病的神经退化和连通性的丧失导致大脑的形态和代谢变化，这些变化可以在磁共振或正电子发射断层扫描图像中看到。然而，这些脑成像方法作为诊断工具，既不具有成本效益，也不便于大规模人群使用。由于可以对眼睛进行无创成像，因此提出了几种通过眼科检查和视网膜成像来检测AD的方法。不幸的是，这些测试都没有被证明是阿尔茨海默病早期阶段的有效指标。该项目旨在通过研究视网膜血流动力学的变化来探索一种有希望的替代方法，用于早期AD的检测。有实验证据表明，AD相关的视网膜血流动力学特定特征的改变出现在AD症状前阶段，使这些特征成为早期诊断的优越指标。本项目将采用多光子显微镜、光学相干断层扫描和光遗传神经刺激等先进技术，结合生物化学和免疫组织化学实验室技术，研究AD在大脑和视网膜的状态和进展之间的相关性。具体而言，我们将探讨AD下静息状态脑和视网膜血流变化与功能性充血中断之间的关系。在本项目中，研究团队将测试这些特征对AD无创早期检测的分析有效性和潜在的临床可行性。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Alzheimer’s disease (AD) is a brain disorder and is the sixth leading cause of death in the United States. AD cannot be slowed or cured should the disease proceed to cognitive decline. Early detection would favor timely intervention to avoid brain cell loss and improve life quality of patients. The main goal of this project is to establish a viable and cost-effective strategy for early detection of AD through a set of relatively simple eye imaging procedures. New optical technologies will be developed to measure changes in eye and brain blood flow associated with AD. Machine learning tools will be deployed to predict the trajectory of the disease. In addition, this project will provide a training opportunity for engineering students to learn about AD and use their engineering skills to contribute to the collective effort of combating this devastating condition.Neural degeneration and loss of connectivity in AD leads to morphological and metabolic changes in the brain that can be visualized in magnetic resonance or positron emission tomography images. However, these brain imaging methods, as diagnostic tools, are neither cost effective nor readily available to large populations. Since the eye is accessible for noninvasive imaging, several procedures have been proposed for detection of AD via ophthalmological examinations and retinal imaging. Unfortunately, none of these tests have proven to be effective indicators of AD at early stages of the disease. This project seeks to explore a promising alternative by studying changes in retinal hemodynamics for early AD detection. There is experimental evidence suggesting that AD-associated changes in specific features of retinal hemodynamics appear in the pre-symptomatic phase of AD making these features superior indicators for early diagnosis. In this project, advanced technologies including multi-photon microscopy, optical coherence tomography, and optogenetic neural stimulation will be developed and employed with biochemical and immunohistochemistry lab techniques, to study the correlation between the state and progression of AD in the brain and retina. Specifically, the relationship between changes in the resting-state cerebral and retinal blood flow and disruption of functional hyperemia under AD will be explored. In this project, the research team will test the analytical validity and potential clinical viability of these features for noninvasive early detection of AD.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.