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.

项目概要/摘要 物理科学公司 (PSI) 提议开发一种新技术来识别淀粉样 β-蛋白 (Aβ) 视网膜中的沉积物作为阿尔茨海默病（AD）的生物标志物。我们这个计划的目标是开发 一种光学成像技术，能够识别视网膜中的体内特定化合物 细胞水平分辨率，非侵入性且无需使用造影剂。我们将验证能力 该技术首先在第一阶段中识别小鼠 AD 的早期迹象，作为原理验证 示范，然后是第二阶段的人类试验。 尽管 AD 尚不能以治愈为目的进行治疗，但足够早的诊断将有助于 使用可用的治疗方法进行干预，为患者的生活增加数年的生产质量时间。 然而，缺乏合适的诊断工具来进行体内 Aβ 聚集的快速筛查和早期诊断。 AD 病理学的检测具有严重的局限性。目前可用的结构、功能和代谢 脑成像方法尚不适合临床前阶段的重复人群筛查。 它们要么受到使用不安全的电离同位素（放射性）的限制，要么成本高，要么性能低 可用性，并提供降低的分辨率或特异性。另一种非侵入性可视化方法 AD 患者中的 Aβ 斑块可以通过视网膜进行高分辨率光学成像，因为知道 Aβ 斑块 在视网膜层中形成并与大脑中的层具有相同的特性。 视网膜作为大脑的延伸，是中枢神经系统中唯一可以被感知的部分。 以亚细胞分辨率进行非侵入性成像。人类死后组织病理学研究 显示 Aβ 在确诊 AD 患者的视网膜中积累，主要是在视网膜内层。 AD 转基因小鼠模型的研究证明了视网膜 Aβ 的存在，并显示 大脑和视网膜 Aβ 沉积之间的定量和时间相关性。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或基于 高光谱成像。然而，迄今为止，还没有涉及光谱分析的活体视网膜成像技术 提供细胞级分辨率，并且没有高分辨率视网膜成像仪器拥有光谱 歧视。 PSI提议开发基于多光谱自适应光学的非侵入式光学成像 该技术将实现体内细胞水平分辨率，以便早期检测视网膜中 Aβ 的存在 并将有助于了解各种神经退行性疾病的发病机制。我们将在此基础上 我们在高分辨率视网膜成像和光谱分析方面的专业知识。