Endotying neurodegeneration through the eye using multimodal retinal imaging

使用多模态视网膜成像通过眼睛内观神经退行性变

• 批准号: 2893169
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2893169
• 关键词: Endotying; neurodegeneration; through; eye; using

Neurodegenerative diseases affect millions of people worldwide and are a global public health challenge. They occur when nerve cells in the brain or peripheral nervous system lose function over time and ultimately die. While no cures currently exist, early detection provides a chance for earlier treatment that may help to prevent or slow disease progression with symptomatic relief to enhance patients' quality of life. However, accurate diagnosis can be challenging. A clinician examining a person to elucidate signs and symptoms over time is usually supported by biomarker data from complex and invasive tests such as MRI and PET imaging and biochemical analysis of cerebrospinal fluid. There is a clinical need for new tests and biomarkers that are quick, less invasive, better tolerated by patients, less expensive, and more accurate [1]. In addition, biomarkers that can predict progression or act as outcome measures in trials of new therapeutics are highly sought.The retina as an accessible part of the human nervous system where we can study nerve cells and small blood vessels [2]. With similarities between the retina and the brain in the composition and structure of cells and vessels and their inflammatory and immunologic reactions to insults combined with the capability to image at a micron level means the eye provides a unique "window" to neurodegeneration and neurovascular dysfunction. Applied to cross-linked datasets collected from patients in Edinburgh has already uncovered evidence of signatures or phenotypes in the eye of diseases affecting the brain such as multiple sclerosis, motor neuron disease, and dementias [3, 4].The SPECTRALIS platform manufactured by our industry partner, Heidelberg Engineering, features 3 types or modes of retinal imaging in one device: Scanning Laser Ophthalmoscopy (SLO) to capture views of the interior surface of the retina featuring the optic nerve head, macula and small blood vessels; Optical coherence tomography (OCT) for cross-sectional imaging of the retina and choroid; OCT-Angiography (OCTA) to image the smallest capillary-level vessel networks. Combining these outputs will enable a detailed characterisation of the vascular systems of the retina and surrounding nerve tissues and further the study of neurodegeneration and neurovascular dysfunction. Generating new insights through the eye will help develop a better understanding, differentiating and monitoring of brain disease, and eventually the development of new therapeutic targets.AimsInvestigate multimodal retinal imaging and analysis as a means of endotyping neurodegeneration.Identify candidate biomarkers derived from imaging for prospective clinical use.Demonstrate the utility of imaging the retina for neurology in diagnosis, prognosis, and monitoring.The specific hypotheses to be examined are:People with different conditions or subtypes of neurodegenerative disease will show significant differences in retinal measures.Retinal measures will correlate with abnormalities found on other clinical tests and brain imaging.Differences in the retina will be evidenced on both cross-sectional and longitudinal measures.Retinal measures will predict patient outcome and/or deterioration.References1. Hansson O. Biomarkers for neurodegenerative diseases. Nat Med. 2021 Jun;27(6):954-963.2. London A, Benhar I, Schwartz M. The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol. 2013 Jan;9(1):44-53.3. Cameron JR (2018). The Eye as a Window to the Brain: investigating the clinical utility of retinal imaging derived biomarkers in the phenotyping of neurodegenerative disease. PhD Thesis, University of Edinburgh, Edinburgh, UK4. Pearson TMC (2019). Multi-modal retinal scanning for diagnostic and therapeutic biomarker discovery in neurodegenerative disease. PhD Thesis, University of Edinburgh, Edinburgh, UK

神经退行性疾病影响着全世界数百万人，是全球公共卫生挑战。当大脑或周围神经系统中的神经细胞随着时间的推移失去功能并最终死亡时，就会发生这种情况。虽然目前没有治愈方法，但早期发现为早期治疗提供了机会，这可能有助于预防或减缓疾病进展，缓解症状，提高患者的生活质量。然而，准确的诊断可能具有挑战性。临床医生检查一个人，以阐明随着时间的推移的体征和症状，通常是由生物标志物数据支持的复杂和侵入性的测试，如MRI和PET成像和脑脊液的生化分析。临床上需要快速、侵入性较小、患者耐受性更好、更便宜且更准确的新检测和生物标志物[1]。此外，可以预测进展或作为新疗法试验结果指标的生物标志物也备受关注。视网膜作为人类神经系统的一个可访问部分，我们可以在其中研究神经细胞和小血管[2]。视网膜和大脑在细胞和血管的组成和结构以及它们对损伤的炎症和免疫反应方面的相似性与在微米级成像的能力相结合意味着眼睛为神经变性和神经血管功能障碍提供了独特的“窗口”。应用于从爱丁堡患者收集的交叉数据集，已经发现了多发性硬化症、运动神经元疾病和痴呆症等影响大脑的疾病的眼部特征或表型的证据[3，4]。SPECTRALIS平台由我们的行业合作伙伴海德堡工程公司制造，在一台设备中具有3种类型或模式的视网膜成像：扫描激光检眼镜检查（SLO）用于捕获视网膜内表面的视图，包括视神经头、黄斑和小血管;光学相干断层扫描（OCT）用于视网膜和脉络膜的横截面成像; OCT血管造影（OCTA）用于对最小的毛细血管网络进行成像。结合这些输出将能够详细描述视网膜和周围神经组织的血管系统，并进一步研究神经变性和神经血管功能障碍。通过眼睛产生新的见解将有助于更好地理解，区分和监测脑部疾病，并最终开发新的治疗靶点。目的研究多模式视网膜成像和分析作为神经变性内分型的一种手段。识别来自成像的候选生物标志物用于前瞻性临床应用。展示视网膜成像在神经病学诊断，预后，和监测。要检查的具体假设是：患有不同条件或神经退行性疾病亚型的人将在视网膜测量中显示出显著差异。视网膜测量将与其他临床测试和脑成像中发现的异常相关。视网膜的差异将在横截面和纵向测量中得到证明。视网膜测量将预测患者的结果和/或恶化。汉森岛神经退行性疾病的生物标志物。自然医学2021年6月;27（6）：954-963.2。放大图片作者：伦敦A，本哈尔I，施瓦茨M.视网膜作为大脑的窗口-从眼科研究到中枢神经系统疾病。天然神经元2013年1月;9（1）：44-53.3。卡梅隆JR（2018）.眼睛作为大脑的窗口：研究视网膜成像衍生生物标志物在神经退行性疾病表型中的临床效用。博士论文，爱丁堡大学，爱丁堡，英国4。Pearson TMC（2019）。多模式视网膜扫描用于神经退行性疾病的诊断和治疗生物标志物发现。英国爱丁堡大学博士论文