He Rosemary, Tward Daniel
Departments of Computer Science and Computational Medicine, University of California, Los Angeles.
Departments of Computational Medicine and Neurology, University of California, Los Angeles.
bioRxiv. 2023 Jan 30:2023.01.11.523671. doi: 10.1101/2023.01.11.523671.
Neurodegeneration measured through volumetry in MRI is recognized as a potential Alzheimer's Disease (AD) biomarker, but its utility is limited by lack of specificity. Quantifying spatial patterns of neurodegeneration on a whole brain scale rather than locally may help address this. In this work, we turn to network based analyses and extend a graph embedding algorithm to study morphometric connectivity from volume-change correlations measured with structural MRI on the timescale of years. We model our data with the multiple random eigengraphs framework, as well as modify and implement a multigraph embedding algorithm proposed earlier to estimate a low dimensional embedding of the networks. Our version of the algorithm guarantees meaningful finite-sample results and estimates maximum likelihood edge probabilities from population-specific network modes and subject-specific loadings. Furthermore, we propose and implement a novel statistical testing procedure to analyze group differences after accounting for confounders and locate significant structures during AD neurodegeneration. Family-wise error rate is controlled at 5% using permutation testing on the maximum statistic. We show that results from our analysis reveal networks dominated by known structures associated to AD neurodegeneration, indicating the framework has promise for studying AD. Furthermore, we find network-structure tuples that are not found with traditional methods in the field.
通过磁共振成像(MRI)容积测量法测得的神经退行性变被认为是一种潜在的阿尔茨海默病(AD)生物标志物,但其效用因缺乏特异性而受到限制。在全脑尺度而非局部量化神经退行性变的空间模式可能有助于解决这一问题。在这项工作中,我们转向基于网络的分析,并扩展了一种图嵌入算法,以研究在数年时间尺度上通过结构MRI测量的体积变化相关性所得到的形态计量学连通性。我们使用多个随机特征图框架对数据进行建模,并修改和实现了先前提出的一种多图嵌入算法,以估计网络的低维嵌入。我们的算法版本保证了有意义的有限样本结果,并从特定人群的网络模式和特定受试者的负荷中估计最大似然边缘概率。此外,我们提出并实施了一种新颖的统计检验程序,以分析在考虑混杂因素后组间差异,并在AD神经退行性变期间定位重要结构。使用对最大统计量进行置换检验,将家族性错误率控制在5%。我们表明,我们的分析结果揭示了由与AD神经退行性变相关的已知结构主导的网络,表明该框架在研究AD方面具有前景。此外,我们发现了该领域传统方法未发现的网络结构元组。