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Window to health: ocular imaging for chronic and systemic disease assessment

健康之窗：用于慢性和全身性疾病评估的眼部成像

基本信息

批准号：
MR/W009293/1
负责人：
Alistair Bounds
金额：
$ 176.73万
依托单位：
Occuity Ltd.
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FW009293%2F1
关键词：
Window health ocular imaging chronic

项目摘要

Chronic and systemic health conditions frequently suffer from a lack of convenient, non-invasive diagnostic tests and imaging instruments, resulting in missed opportunities to detect illnesses early and causing increased patient suffering, missed opportunities for early intervention, worse outcomes, and increased costs. The eye offers unique insight into several chronic and systemic conditions. Blood vessels in the retina are shared with brain blood vessels, and when blood vessels in the brain experience disruption, this is often associated with retinal blood vessel disruption (e.g. malarial retinopathy in cerebral malaria). Protective barriers (the blood-brain and blood-retina barriers) in the smallest blood vessels prevent large molecules and pathogens such as viruses passing from blood into the retina and brain, and the breakdown of these barriers can lead to a range of chronic ocular and neurodegenerative conditions.Understanding what is happening in the eye can therefore tell us what is happening in the brain. Imaging of the eye is already routinely practiced, and can be conducted quickly and non-invasively, but this is currently targeted primarily at understanding the health of the retina by looking at changes in retinal structure, rather than being used to understand the brain or detecting molecular and blood flow changes. I will develop state-of-the-art retinal imaging systems and techniques to detect retinal indicators of chronic and systemic conditions.I will build a fluorescence lifetime imaging ophthalmoscope, to detect molecular spectral signatures and detect the presence of biomarkers across the retina. This system will use state-of-the-art single-photon detector arrays from the University of Edinburgh to achieve the most thorough assessment of retinal molecular composition ever. This system will then be used to investigate two key conditions, Alzheimer's disease and diabetic retinopathy. In the first stage of this fellowship, I will collaborate with clinical partners as part of existing research programmes to obtain preliminary evidence of molecular signatures of disease, which will be used to pursue larger clinical research projects in the second stage of this fellowship. This research programme builds on the scanning confocal and fluorescence imaging techniques already developed by Occuity that target the lens. Potential commercialisation of this system will be built on a diverse long-term collaboration between multiple industry and academic partners developed in this second stage. I will also develop a laser speckle contrast imaging system to assess retinal microvascular blood flow. Although laser speckle contrast imaging has already been used to assess retinal blood flow in large blood vessels, microvascular changes are far more relevant for conditions such as diabetic retinopathy and septic shock. Combining emerging multiple-exposure speckle imaging techniques with image stabilisation techniques pioneered by Occuity and utilising advances in camera technology, quantitative microvascular flow measurements will be demonstrated and validated through comparisons to existing methods such as optical coherence tomography angiography and fundus fluorescein angiography that are either invasive or prohibitively slow. Collaborating with clinical partners with existing research programmes, I will then demonstrate the potential usefulness of the system investigating septic shock and diabetic retinopathy and generate the preliminary evidence necessary to establish larger clinical research projects in the second stage of this project. I will also develop a commercial prototype during the first stage of this project, supported by a market assessment and commercialisation case study, setting the ground for market translation in the second stage of this fellowship.

慢性和全身性健康状况经常受到缺乏方便的非侵入性诊断测试和成像仪器的困扰，导致错过了早期发现疾病的机会，并导致患者痛苦增加，错过了早期干预的机会，结果更糟，成本增加。眼睛提供了对几种慢性和全身性疾病的独特见解。视网膜中的血管与脑血管共享，并且当脑中的血管经历破裂时，这通常与视网膜血管破裂（例如，脑疟疾中的疟疾性视网膜病变）相关。最小血管中的保护屏障（血脑屏障和血视网膜屏障）阻止大分子和病原体（如病毒）从血液进入视网膜和大脑，这些屏障的破坏可导致一系列慢性眼部和神经退行性疾病。因此，了解眼睛中发生的情况可以告诉我们大脑中发生了什么。眼睛成像已经是常规实践，并且可以快速和非侵入性地进行，但目前主要是通过观察视网膜结构的变化来了解视网膜的健康状况，而不是用于了解大脑或检测分子和血流变化。我将开发最先进的视网膜成像系统和技术，以检测慢性和系统性疾病的视网膜指标。我将建立一个荧光寿命成像检眼镜，以检测分子光谱特征，并检测整个视网膜的生物标志物的存在。该系统将使用爱丁堡大学最先进的单光子探测器阵列，以实现有史以来最彻底的视网膜分子组成评估。然后，该系统将用于研究两种关键疾病，阿尔茨海默病和糖尿病视网膜病变。在该奖学金的第一阶段，我将与临床合作伙伴合作，作为现有研究计划的一部分，以获得疾病分子特征的初步证据，这些证据将用于在该奖学金的第二阶段进行更大的临床研究项目。这项研究计划建立在占领已经开发的扫描共聚焦和荧光成像技术的目标透镜。该系统的潜在商业化将建立在第二阶段开发的多个行业和学术合作伙伴之间的长期合作基础上。我还将开发一个激光散斑对比成像系统，以评估视网膜微血管血流。虽然激光散斑对比成像已经被用于评估大血管中的视网膜血流，但微血管变化与糖尿病视网膜病变和感染性休克等疾病更为相关。结合新兴的多次曝光散斑成像技术与Occuity开创的图像稳定技术，并利用相机技术的进步，定量微血管流量测量将通过与现有方法（如光学相干断层扫描血管造影术和眼底荧光素血管造影术）的比较进行证明和验证，这些方法要么是侵入性的，要么是非常缓慢的。与现有研究项目的临床合作伙伴合作，我将展示该系统调查感染性休克和糖尿病视网膜病变的潜在有用性，并在该项目的第二阶段产生建立更大的临床研究项目所需的初步证据。我还将在该项目的第一阶段开发一个商业原型，并进行市场评估和商业化案例研究，为该奖学金第二阶段的市场翻译奠定基础。