Multispectral cellular-level retinal imaging for early detection of Alzheimer’s disease

用于早期检测阿尔茨海默病的多光谱细胞水平视网膜成像

• 批准号: 10323717
• 负责人: Mircea Mujat
• 金额: $ 26.31万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10323717
• 关键词: Address; Affect; Age; Algorithmic Software; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Animals; Autopsy; Blood; Brain; Brain imaging; Chemicals; Clinic; Computer software; Contrast Media; Curcumin; Deposition; Detection; Development; Diagnostic; Discrimination; Disease Progression; Early Diagnosis; Evaluation; FDA approved; Fluorescence; Goals; Government; Human; Human Volunteers; IACUC; Image; Imaging Device; Imaging Techniques; Imaging technology; Intervention; Ions; Isotopes; Laboratory Research; Letters; Life; Lighting; Measures; Metabolic; Mus; Neuraxis; Neurodegenerative Disorders; Oxygen saturation measurement; Pathology; Patients; Persons; Phase; Play; Population; Positron-Emission Tomography; Property; Protocols documentation; Radioactivity; Rapid screening; Rattus; Recording of previous events; Research; Research Personnel; Resolution; Retina; Science; Specificity; Structure; Techniques; Technology; Testing; Therapeutic; Time; Training; Transgenic Mice; abeta accumulation; adaptive optics; amyloid imaging; base; cognitive function; cost; design; drug development; fluorescence imaging; imager; imaging modality; imaging platform; in vivo; instrument; mouse model; multimodality; non-invasive optical imaging; novel; novel strategies; optical imaging; physical science; pre-clinical; programs; protein aggregation; retinal imaging; screening; success; tool; transmission process; treatment response

Project Summary/Abstract Physical Sciences Inc (PSI) proposes to develop a novel technique to identify amyloid β-protein (Aβ) deposits in the retina as a biomarker for Alzheimer's disease (AD). Our goal in this program is to develop an optical imaging technique capable of identifying specific chemical compounds in vivo in the retina with cellular-level resolution, non-invasively, and without the use of contrast agents. We will validate the ability of this technique to identify early indications of AD on mice first in Phase I as a proof-of-principle demonstration, and then on humans in Phase II. Although AD cannot yet be treated with the intent to cure, sufficiently early diagnosis will facilitate intervention with available therapeutics, adding years of productive quality time to the patient's life. However, the lack of suitable diagnostic tools for both in vivo rapid screening of Aβ aggregation and early detection of AD pathology poses severe limitations. Current available structural, functional, and metabolic brain imaging methods are not yet suitable for repeated population screening in the preclinical stages. They are either limited by the use of unsafe ionizing isotopes (radioactivity), involve high costs, have low availability, and provide reduced resolution or specificity. An alternative non-invasive approach to visualize Aβ plaques in AD patients could be high-resolution optical imaging of the retina, knowing that Aβ plaques form in retinal layers and share properties with those in the brain. The retina, as an extension of the brain, is the only part of the central nervous system that can be imaged non-invasively at sub-cellular resolutions. Human postmortem histopathological studies have shown accumulation of Aβ in the retinas of those with confirmed AD, principally in the inner-retinal layers. Studies of transgenic mouse models of AD have demonstrated the presence of retinal Aβ and shown quantitative and temporal correlations between brain and retinal Aβ deposition. Most of the in vivo retinal imaging techniques involved fluorescence imaging based on curcumin as a fluorescence tag or on hyperspectral imaging. However, so far, no in vivo retinal imaging technique involving spectral analysis provided cellular-level resolution and no high-resolution retinal imaging instrument possessed spectral discrimination. PSI proposes to develop a multispectral adaptive optics-based non-invasive optical imaging technique that will enable in vivo cellular-level resolution for early detection of Aβ presence in the retina and will facilitate a path to understanding the onset of various neurodegenerative diseases. We will build on our expertise in high-resolution retinal imaging and spectral analysis.

项目摘要/摘要 物理科学公司（PSI）提案，以开发一种新技术来鉴定淀粉样蛋白β-蛋白质（Aβ） 作为阿尔茨海默氏病（AD）的视网膜沉积物作为生物标志物。我们在该计划中的目标是发展 一种光学成像技术，能够在视网膜中鉴定特定的化学化合物， 细胞水平的分辨率，无侵入性，不使用对比剂。我们将验证能力 这项技术是首先在第一阶段识别小鼠的早期迹象作为原理证明 示范，然后在第二阶段的人类。 尽管AD尚无法治愈目的，但足够的早期诊断将有助于 干预可用的治疗，为患者的生活增加了多年的产品质量时间。 但是，缺乏用于体内快速筛查Aβ聚集和早期的诊断工具 检测AD病理位置的严重局限性。当前可用的结构，功能和代谢 脑成像方法尚不适合在临床前阶段重复进行种群筛查。 它们要么受到使用不安全的电离同位素的限制（放射性），涉及高成本，较低 可用性，并提供降低的分辨率或特异性。可视化的另一种非侵入性方法 AD患者的Aβ斑块可能是视网膜的高分辨率光学成像，知道Aβ斑块 在残留层中形成并与大脑中的属性共享。 视网膜作为大脑的扩展，是中枢神经系统的唯一部分 在亚细胞分辨率下进行非侵入性成像。人类验尸组织病理学研究 显示Aβ在具有确认AD的视网膜中的积累，主要是在视网膜层中。 AD的转基因小鼠模型的研究表明存在残留Aβ，并显示了 大脑与视网膜Aβ沉积之间的定量和临时相关性。大多数体内视网膜 成像技术涉及基于姜黄素作为荧光标签的荧光成像或 高光谱成像。但是，到目前为止，没有涉及光谱分析的体内视网膜成像技术 提供了细胞水平的分辨率，没有具有光谱的高分辨率视网膜成像仪 歧视。 PSI提出的提议开发基于多光谱的基于自适应光学的非侵入性光学成像 将使体内细胞级分辨率的技术早期检测到视网膜中的Aβ存在 并将促进理解各种神经退行性疾病的开始的途径。我们将基础 我们在高分辨率视网膜成像和光谱分析方面的专业知识。