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

研究阿尔茨海默病视网膜局部神经刺激的脑血流反应变化作为早期诊断的潜在机制

• 批准号: 2154267
• 负责人: Ramin Pashaie
• 金额: $ 65.8万
• 依托单位: Florida Atlantic University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154267&HistoricalAwards=false
• 关键词: Investigating; changes; cerebral; blood; flow

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.

阿尔茨海默氏病（AD）是一种脑部疾病，是美国第六大死亡原因。如果疾病继续认知下降，AD不能缓慢或治愈。早期检测将有利于及时干预，以避免脑细胞损失并改善患者的生活质量。该项目的主要目标是通过一组相对简单的眼部成像程序建立可行且具有成本效益的策略，以早日检测AD。将开发新的光学技术来衡量与AD相关的眼睛和脑血流的变化。机器学习工具将被部署以预测疾病的轨迹。此外，该项目将为工程专业的学生提供培训机会，以了解广告并利用其工程技能来促进梳理这种毁灭性状况的集体努力。广告中的神经退化和连接性丧失会导致大脑中的形态和代谢变化，这些变化可以在磁共振或积极的发射层析图像中可视化。但是，作为诊断工具作为诊断工具，这些大脑成像方法既不是具有成本效益的，也不容易获得大量人群。由于可用于非侵入性成像的眼睛，因此已经提出了几种通过眼科检查和视网膜成像检测AD的程序。不幸的是，这些测试都没有被证明是在疾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承诺替代方案。有实验证据表明，视网膜血流动力学特定特征的特定特征的变化出现在AD的症状前阶段，从而使这些特征具有早期诊断的特征指标。在该项目中，将开发和使用用于研究和免疫组织化学实验室技术，包括多光子显微镜，光学相干断层扫描以及光遗传学中性刺激，以研究脑和脑中AD的相关性。具体而言，将探讨静息状态大脑和残留血流的变化与AD下功能充血的破坏之间的关系。在该项目中，研究团队将测试这些功能的分析有效性和潜在的临床可行性，以验证AD的非侵入性早期检测。该奖项反映了NSF的法定任务，并通过使用该基金会的知识分子的优点和更广泛的影响来评估NSF的法定任务。