Using the eye to unlock changes in the health of the aging brain: a state of the art data analysis approach

随着年龄的增长，人们的大脑和身体退化的程度差别很大。随着年龄的增长，认知能力下降，从正常的认知老化到不同的痴呆症。个体之间衰退差异的决定因素尚未完全理解，并且在我们的社会寻求应对人口老龄化带来的挑战时存在重大知识差距[1]。磁共振成像已被用于调查的患病率和机制，年龄相关的变化，如血管完整性的大脑。特别重要的是小血管的健康-对这些内衬的损害可以看到这种屏障的失败和材料泄漏到脑组织中，这会导致进一步的损伤并导致认知能力下降。由于其分辨率的限制，使用常规MR成像不可能直接评估大脑的微血管，但是可以直接对视网膜微血管进行成像，并且由于其与大脑的微血管具有相似的胚胎学起源以及解剖学和生理学特性，因此眼睛提供了独特的“窗口”来研究体内微血管变化，其反映了大脑中发生的类似变化[2]。该项目将通过利用我们小组的背景工作和现有的数据存储库LBC 1936来研究与年龄相关的认知衰退背景下的视网膜，该数据存储库具有目前约82岁的老年人的非常良好的纵向队列[3]。在过去的12年里，沿着定期收集对认知、身体活动和健康的评估，以及详细的大脑MR图像和视网膜眼底图像。通过分析这些相关数据，包括结构方程建模和卷积神经网络等技术，学生将研究在晚年重要时期发生的视网膜，大脑和认知中与年龄相关的变化之间的关系。该项目将研究从视网膜测量的参数，以帮助预测或模拟老年人认知变化的轨迹，将正常的认知老化与明显的退化分开。学生将参与成像的多个方面，从采集到图像测量和数据分析。他们将投入到吸血鬼项目中，这是爱丁堡大学和邓迪大学之间的一项为期15年的联合计划，由提议者MacGillivray和Trucco指导，该计划正在建立一个世界级的视网膜分析专业知识虚拟中心。在VAMPIRE和LBC团队成员的支持下，学生将学习最先进的数据分析技术，并将其作为研究大脑健康视网膜生物标志物的尖端手段。学生将通过参加各自大学合作伙伴提供的课程获得关键技能，包括爱丁堡成像学院的在线材料，并与我们研究小组的专家成员互动。到项目结束时，学生将成为视网膜成像和分析方面的专家，并将研究传统的生物标志物（即临床，认知和MR成像）和新的视网膜终点。Deary，I.J.，例如，脑卒中相关的认知能力下降。Br Med Bull，2009年。92：第135-52.2页。巴顿，N.，例如，视网膜血管图像分析作为脑血管疾病的潜在筛查工具：基于脑和视网膜微血管同源性的基本原理。J Anat.2005. 206（4）：第319-348.3页。Deary，I.J.，例如，队列概况：1921年和1936年的洛锡安出生队列。国际流行病学杂志，2012年。41（6）：p. 1576-84.

People differ greatly in the degree to which their brains and bodies deteriorate with age. With ageing comes a decline in cognitive ability, a spectrum ranging from normal cognitive ageing through to different dementias. The determinants of the differences in decline between individuals are not fully understood and represent a significant knowledge gap as our society looks to meet the challenges presented by an ageing population [1]. MR imaging has been used to investigate the prevalence of and mechanisms for age-related changes in the brain such as vascular integrity. Of particular importance is the health of small blood vessels - damage to the lining of these can see failure of this barrier and leakage of material into brain tissue, which cause further injury and leads to cognitive decline. Direct assessment of the brain's microvasculature is not possible with routine MR imaging due to the limitations of its resolution but the retinal microvascular be can imaged directly and as it shares similar embryological origins and anatomical and physiological properties with the brain's microvasculature, the eye provides a unique "window" to study microvascular changes in vivo that reflect similar changes occurring in the brain [2]. This project will investigate the retina in the context of age-related cognitive decline by leveraging background work by our group and an existing data repository, LBC1936, that features an exceptionally well-characterised longitudinal cohort of elderly individuals currently ~82 years old [3]. Assessments of cognition, physical activity and health have been collected at regular intervals over the past 12 years along with detailed MR images of the brain and retinal fundus images. Through analysis of this linked data, including techniques such as structural equation modelling and convolutional neural networks, the student will investigate the relationships between age-related changes in the retina, brain and cognition that have occurred in individuals over an important period of later life. The project will look at parameters measured from the retina helping to predict or model the trajectory of cognitive change in the elderly, separating out normal cognitive ageing from pronounced deterioration. The student will engage with multiple aspects of imaging from acquisition to image measurement and data analysis. They will feed into the VAMPIRE project, a 15-year joint initiative between the Universities of Edinburgh and Dundee, directed by proposers MacGillivray and Trucco, which is building a world-class virtual centre of expertise in retinal analysis. The student, with support from members of the VAMPIRE and LBC teams, will learn about state-of-the-art data analysis techniques and apply these as a cutting-edge means of investigating retinal biomarkers of brain health. The student will gain key skills by attending courses offered by the respective university partners including on-line materials in the Edinburgh Imaging Academy and interact with the expert members of our research group. By the end of the project, the student will themselves be expert in retinal imaging and analysis and will have investigated conventional biomarkers (i.e. clinical, cognitive and MR imaging) and novel retinal endpoints.1. Deary, I.J., et al., Age-associated cognitive decline. Br Med Bull, 2009. 92: p. 135-52.2. Patton, N., et al., Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures. J Anat. 2005. 206(4): p. 319-348.3. Deary, I.J., et al., Cohort profile: the Lothian Birth Cohorts of 1921 and 1936. Int J Epidemiol, 2012. 41(6): p. 1576-84.