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

核磁共振等医学成像技术已经彻底改变了疾病的临床诊断、治疗和监测。然而，它们价格昂贵，而且在专科单位之外不易获得。想象一下，如果有一种可以提供一系列疾病诊断信息的商业街视力测试。这些疾病可能是阿尔茨海默氏症等神经退行性疾病、心脏病等全身性疾病或抑郁症等精神疾病。这项测试将是敏感的，在任何症状显现和不可弥补的损害发生之前就能检测到疾病的特征，并允许对治疗后的变化进行精细的监测。它将提供特异性，区分不同病因但相似视网膜表现的疾病。这将允许对疾病进展的机械性理解，为未来的治疗铺平道路。实现这一愿景的关键是应用从显微镜、图像和信号处理到活着的人类视网膜的高分辨率光学成像的最新技术进步。视网膜是我们眼睛后面的组织，实际上是中枢神经系统的一部分，长期以来一直被认为是通往大脑和血管系统的窗口。事实上，精神疾病、神经退行性疾病和全身性疾病已经被证明与眼睛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区分疾病的大体解剖变化。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，以灵敏和特异地检测这些疾病。这项技术将对一系列疾病提供快速、非侵入性的诊断，取代昂贵、耗时的当前黄金标准方法，从而彻底改变医疗保健点医学。我们的团队是技术开发人员和眼科专家之间的合作，涵盖合作机构内的工程和医学科学。我们已经拥有了使用定制光学仪器进行终身人体参与测试的经验，并在技术商业化、产业合作和衍生产品方面拥有丰富的经验。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、全息照相以及专用图像和信号处理--在显微镜和眼底镜的相关领域都是可用的，但提供一套集成的仪器仍然是一项重大的工程挑战。开发阶段将是至关重要的，以建立原则证明示范，以吸引利益相关者，并将努力集中在那些最有可能对医疗保健产生“颠覆性”影响的领域。利益相关者--临床医生、行业合作伙伴和患者团体--将通过当地NHS信托基金和教学医院、现有的行业网络和代表特定患者队列的慈善机构进行接触。在发展阶段，我们将扩大和深化这些网络。从长远来看，我们将参与所有级别的医学培训-从临床前本科生到既定的顾问。社会面临的三个重大挑战是心理健康问题在整个人口中的高发病率、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，在老龄化社会中非常令人担忧。痴呆症和心脏病是英国乃至世界范围内的主要死亡原因。对这种令人衰弱的疾病进行更快、更有效的诊断和治疗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.