Computational Modelling of Ageing Brains: Virtual Populations for In Silico Clinical Trials

英国人口正在老龄化，2019年有五分之一的人年龄在65岁或以上，预计到2043年将上升到24%。这伴随着慢性疾病、中风、痴呆和房颤的风险增加。该项目旨在为计算机临床试验和医疗器械开发老化血管模型。将开发经验证的脑血管老化模型，以生成用于年龄相关脑血管疾病及其治疗的计算机临床试验的老化虚拟人群。使用容易获得的数据，将从对应于生理信号的数据（例如，脑血流量、血压）。将利用大脑大血管中血流的一维模型创建一个个性化的计算机老化模型。一个逆问题，用于校准单个患者解剖结构的模型，创建这些患者的数字双胞胎。然后，通过将一维血流模型与微循环模型相结合来模拟不同年龄段的脑血管疾病，从而创建虚拟大脑的老龄化人群。这将根据真实的患者数据进行验证，以确认模型的准确性并评估其每个参数的影响。其结果将是一个经过验证的脑血管老化模型，可以根据生理年龄预测疾病结果，使脑血管研究，医疗设备/药物开发以及研究与年龄相关的脑疾病（如痴呆症和阿尔茨海默氏症）的虚拟人群成为现实。

The UK population is ageing, with one-fifth aged 65 or over in 2019 and projected to rise to 24% by 2043. This is accompanied by an increased risk of chronic diseases, stroke, dementia, and atrial fibrillation. This project aims to develop models of the ageing cerebrovasculature for in silico clinical trials and medical device development. Validated models of cerebrovascular ageing will be developed to generate an ageing virtual population for in silico clinical trials of age-related cerebrovascular disease and its treatment. Using readily available data, patient "digital twins" will be created from data corresponding to physiological signals (e.g., cerebral blood flow, blood pressure) from healthy and diseased participants of different ages. A personalised in silico ageing model will be created utilising a one-dimensional model of blood flow in the brain's large vessels. An inverse problem to calibrate the model for individual patient anatomies, creating digital twins of those patients. Ageing populations of virtual brains will then be created by combining the one-dimensional blood flow model with a microcirculation model to simulate cerebrovascular disease in different age ranges. This will be validated against real patient data to confirm the accuracy of the model and assess the impact of each of its parameters. The outcome will be a validated model of cerebrovascular ageing to predict disease outcomes based on physiological age, enabling realistic virtual populations for cerebrovascular research, medical device/drug development, and investigating age-related cerebral diseases like dementia and Alzheimer's.