Detecting, tracking & modelling structural and functional brain imaging changes in Alzheimer's disease

检测、跟踪

• 批准号: MR/J014257/2
• 负责人: Gerard Ridgway
• 金额: $ 29.52万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ014257%2F2
• 关键词: Detecting; tracking; modelling; structural; functional

Dementia is a major and growing public health challenge and a research priority in the developed world. According to Alzheimer's Research UK, 25 million people in Britain have a family member or close friend with dementia, and the cost to our economy is estimated to be £23-billion per year.There are currently only symptomatic treatments for Alzheimer's disease (AD); no 'disease-modifying' drugs. A lot of current research work relates to the search for these much needed disease-modifying treatments. Improved methods for assessing disease progression would increase the chances of showing that an intervention slowed the course of decline.Structural changes, measurable on brain scans (magnetic resonance imaging; MRI) have been shown to predate and predict symptom onset and correlate with clinical decline in AD, and may help to evaluate potential disease-modifying therapies. Scans which appear visually normal to an expert might have subtle pathology detectable with computational analysis. There is emerging evidence that functional brain imaging (fMRI) can reveal changes even earlier in the course of the disease, and that these changes are associated with clinical measures like memory performance. There is a strong need for more precise characterisation of both structural and functional change, and for better understanding of the interactions between structure and function.I will work to address these challenging problems in my Fellowship by developing new methods at the Wellcome Trust Centre for Neuroimaging, and applying these methods to large patient data-sets in collaboration with the Dementia Research Centre. Both Centres are part of the world-renowned UCL Institute of Neurology, at University College London.My first objective is to develop a new statistical model for longitudinal structural imaging data (multiple brain scans over time), and to apply this to the problem of diagnosis and tracking of AD. This will allow hypotheses about the regional localisation of atrophy and its acceleration to be tested with greater power (i.e. we should be able to find changes using the new model that are undetectable without it).My second aim is to investigate methods for modelling the connectivity among different brain regions, using fMRI acquired with subjects 'at rest'. Such data, and the brain networks that it can reveal, are generating increasing interest in the scientific and clinical research communities. Even in the very early stages of dementia, there may be changes in the way one brain region communicates with another. Reductions in these changes with a potential drug therapy could indicate success of that drug much earlier than clinical symptoms like memory loss. The utility of such 'biomarkers' from fMRI for dementia is currently an under-researched topic with great potential for detecting early changes and providing new outcome measures for treatment trials.Finally, I aim to use the new methods together to investigate the inter-relation of structure and function and their changes in the disease. This will allow me to evaluate the power of the novel structural, functional and combined multi-modal measures for tracking disease progression. This has significant potential to provide better outcome measures for clinical trials, in terms of detecting change more robustly, less variably, or earlier in the disease course, with consequent impact on the search for disease-modifying treatments.

痴呆症是一项日益严重的重大公共卫生挑战，也是发达国家的研究重点。根据英国阿尔茨海默氏症研究所的数据，英国有2500万人的家庭成员或亲密朋友患有痴呆症，据估计，英国经济每年的损失为230亿英镑。目前阿尔茨海默病（AD）只有对症治疗；没有“改善疾病”的药物。目前的许多研究工作都与寻找这些急需的改善疾病的治疗方法有关。评估疾病进展的改进方法将增加表明干预减缓了衰退过程的机会。脑部扫描（磁共振成像；MRI）可测量的结构变化已被证明可以提前和预测症状发作，并与阿尔茨海默病的临床衰退相关，并可能有助于评估潜在的疾病改善疗法。在专家看来视觉上正常的扫描可能有细微的病理，可以通过计算分析检测出来。越来越多的证据表明，功能性脑成像（fMRI）可以揭示疾病早期的变化，而这些变化与记忆表现等临床指标有关。我们迫切需要更精确地描述结构和功能变化，以及更好地理解结构和功能之间的相互作用。我将通过在威康信托神经成像中心开发新方法，并与痴呆症研究中心合作，将这些方法应用于大型患者数据集，来解决这些具有挑战性的问题。这两个中心都是世界著名的伦敦大学学院神经病学研究所的一部分。我的第一个目标是为纵向结构成像数据（一段时间内多次脑部扫描）开发一种新的统计模型，并将其应用于AD的诊断和跟踪问题。这将允许对萎缩的区域定位及其加速的假设进行更有力的测试（即，我们应该能够使用新模型发现没有它无法检测到的变化）。我的第二个目标是研究不同大脑区域之间连接的建模方法，使用在受试者“休息”时获得的功能磁共振成像。这样的数据，以及它所揭示的大脑网络，正在引起科学和临床研究界越来越大的兴趣。即使在痴呆症的早期阶段，一个大脑区域与另一个大脑区域的沟通方式也可能发生变化。这些变化的减少与潜在的药物治疗可能表明药物的成功比临床症状如记忆丧失要早得多。从功能磁共振成像（fMRI）中提取的这种“生物标志物”对痴呆症的效用目前是一个研究不足的课题，在检测早期变化和为治疗试验提供新的结果测量方面具有很大的潜力。最后，我的目标是将这些新方法结合起来研究结构和功能的相互关系及其在疾病中的变化。这将使我能够评估用于跟踪疾病进展的新型结构、功能和组合多模式措施的力量。这有很大的潜力为临床试验提供更好的结果测量，在更稳健、更少变化或更早的疾病过程中检测变化，从而对寻找改善疾病的治疗产生影响。

项目成果

Real-time decoding of covert attention in higher-order visual areas.

• DOI: 10.1016/j.neuroimage.2017.12.019
• 发表时间: 2018-04-01
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Ekanayake J;Hutton C;Ridgway G;Scharnowski F;Weiskopf N;Rees G
• 通讯作者: Rees G

White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy.

• DOI: 10.1002/hipo.22690
• 发表时间: 2017-03
• 期刊: Hippocampus
• 影响因子: 3.5
• 作者: Fiford CM;Manning EN;Bartlett JW;Cash DM;Malone IB;Ridgway GR;Lehmann M;Leung KK;Sudre CH;Ourselin S;Biessels GJ;Carmichael OT;Fox NC;Cardoso MJ;Barnes J;Alzheimer's Disease Neuroimaging Initiative
• 通讯作者: Alzheimer's Disease Neuroimaging Initiative

Failed replications, contributing factors and careful interpretations: Commentary on Boekel et al., 2015.

• DOI: 10.1016/j.cortex.2015.02.019
• 发表时间: 2016-01
• 期刊: Cortex; a journal devoted to the study of the nervous system and behavior
• 作者: Muhlert N;Ridgway GR
• 通讯作者: Ridgway GR

Accurate automatic estimation of total intracranial volume: a nuisance variable with less nuisance.

• DOI: 10.1016/j.neuroimage.2014.09.034
• 发表时间: 2015-01-01
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Malone IB;Leung KK;Clegg S;Barnes J;Whitwell JL;Ashburner J;Fox NC;Ridgway GR
• 通讯作者: Ridgway GR

Patterns of atrophy in pathologically confirmed dementias: a voxelwise analysis.

• DOI: 10.1136/jnnp-2016-314978
• 发表时间: 2017-11
• 期刊: Journal of neurology, neurosurgery, and psychiatry
• 作者: Harper L;Bouwman F;Burton EJ;Barkhof F;Scheltens P;O'Brien JT;Fox NC;Ridgway GR;Schott JM
• 通讯作者: Schott JM