PREDICTOR - PRE-symptomatic DIagnosis through adaptive optiCal Tomographic sensing Of the Retina

磁共振成像等医学成像技术已经彻底改变了临床诊断、治疗和疾病监测。然而，它们价格昂贵，而且在专科单位以外不易获得。想象一下，如果有一种普通的视力测试可以提供一系列疾病的诊断信息。这些疾病可能是神经退行性疾病，如阿尔茨海默氏症，全身性疾病（对身体有广泛影响的疾病），如心脏病，或精神疾病，如抑郁症。这种测试将是敏感的，在任何症状出现之前，在不可挽回的损害发生之前，就能捕捉到疾病的特征，并允许对治疗反应的变化进行精细的监测。它将提供特异性，区分不同病因但视网膜表现相似的疾病。这将有助于对疾病进展的机制理解，为未来的治疗铺平道路。实现这一愿景的关键是应用最新的技术进步，从显微镜、图像和信号处理到活体人类视网膜的高分辨率光学成像。视网膜是我们眼睛后部的组织，实际上是中枢神经系统的一部分，长期以来一直被认为是大脑和脉管系统的窗口。事实上，精神疾病、神经退行性疾病和全身性疾病在眼睛中都有可检测到的相关性。然而，目前的临床技术无法对单个细胞进行成像，因此这些疾病表现为无法在疾病之间区分的大体解剖变化。我们将开发一种非侵入性光学仪器，能够对单个细胞进行成像并测试其功能，以便对这些疾病进行敏感和特异性检测。这项技术将通过对一系列疾病提供快速、非侵入性的诊断，取代目前昂贵、耗时的黄金标准方法，从而彻底改变即时医疗。我们的团队是技术开发人员和眼科专家之间的合作，跨越合作机构的工程和医学科学。我们已经拥有在整个生命周期内使用定制光学仪器进行人体参与者测试的经验，以及在技术商业化、工业伙伴关系和衍生产品方面的丰富经验。所需的技术组件-例如，光学干涉测量，自适应光学，光谱和偏振技术，全息术，以及专用的图像和信号处理-在显微镜和眼科检查的相关领域是可用的，但是提供一个集成的仪器包仍然是一个重大的工程挑战。开发阶段对于建立原理验证演示以吸引利益相关者，并将努力瞄准那些最有可能对医疗保健产生“破坏性”影响的领域至关重要。利益相关者——临床医生、行业合作伙伴和患者群体——将通过当地的NHS信托基金和教学医院、现有的行业网络和代表特定患者群体的慈善机构参与进来。在开发阶段，我们将扩大和深化这些网络。从长远来看，我们将参与各级医学培训——从临床前的本科生到成熟的咨询师。社会面临的三个重大挑战是人口中精神健康问题的高发率、心血管疾病和神经退行性疾病，这些疾病对老年人的影响不成比例，在老龄化社会中引起了极大关注。痴呆和心脏病是英国乃至全世界的主要死亡原因。更快、更有效地诊断和治疗这些使人衰弱的疾病将显著改善这些患者的预后。这项技术的广泛应用将通过商业化带来新的业务增长。

Medical imaging techniques such as MRI have revolutionised clinical diagnosis, treatment and monitoring of disease. However, they are expensive and not readily accessible outside specialist units. Imagine if instead, there was available a high-street eye test that provided diagnostic information for a range of diseases. These diseases could be neurodegenerative diseases such as Alzheimer's, systemic diseases (diseases with wide-spread effect on the body) such as heart disease, or psychiatric conditions, such as depression. The test would be sensitive, picking-up signatures of disease before any symptoms were apparent and before irreparable damage had occurred, and allowing fine scale monitoring of changes in response to treatment. It would offer specificity, differentiating between diseases with different aetiologies but similar retinal manifestations. This would allow mechanistic understanding of disease progression, paving the way for future therapies. The key to realising this vision is the application of recent technological advances from microscopy, image and signal processing to high-resolution optical imaging of the living human retina. The retina, which is the tissue at the back of our eye, is in fact a part of the central nervous system and has long been recognised as a window to the brain and vasculature. In fact, psychiatric, neurodegenerative, and systemic diseases have been shown to have detectable correlates in the eye. However, current clinical technology cannot image individual cells, and so these diseases manifest in gross anatomical changes that cannot be distinguished amongst diseases. We will develop a non-invasive optical instrument, capable of imaging individual cells and testing their function, for sensitive and specific detection of these diseases. The technology would revolutionise point-of-care medicine by providing rapid, non-invasive diagnostics on a range of conditions, replacing costly, time-consuming current gold standard methods. Our team is a collaboration between technology developers and ophthalmic specialists, spanning engineering and medical science within partner institutions. We already have experience in human participant testing across the life-span with bespoke optical instrumentation, and extensive experience in commercialisation of technology, industrial partnership and spin-outs. The required technological components - for example, optical interferometry, adaptive optics, spectroscopic and polarisation techniques, holography, and dedicated image and signal processing - are available in the related fields of microscopy and ophthalmoscopy, but delivering an integrated instrumentation package remains a significant engineering challenge. The development phase will be vital for establishing proof-of-principle demonstrations to engage stakeholders, and to target efforts to those areas that are most likely to have 'disruptive' impact in healthcare. Stakeholders - clinicians, industry partners and patient groups - will be engaged through local NHS Trusts and teaching hospitals, existing industry networks and charities representing specific patient cohorts. During the development phase we will widen and deepen these networks. With a long-term view, we will engage at all levels of medical training - from the pre-clinical undergraduate to the established consultant. Three significant challenges facing society are the high incidence of mental health issues across the population, cardiovascular disease, and neurodegenerative diseases which disproportionately affect the elderly and are of great concern in an ageing society. Dementia and heart disease are the leading causes of death in the UK, and indeed world-wide. Faster and more effective diagnosis and treatment of such debilitating conditions will significantly improve outcomes for these patients. Widespread uptake of the technology will lead to new business growth through commercialisation.