Mild traumatic brain injury (mTBI) is a complex syndrome that affects up to 600 per 100,000 individuals, with a particular concentration among military personnel. About half of all mTBI patients experience a diverse array of chronic symptoms which persist long after the acute injury. Hence, there is an urgent need for better understanding of the white matter and gray matter pathologies associated with mTBI to map which specific brain systems are impacted and identify courses of intervention. Previous works have linked mTBI to disruptions in white matter pathways and cortical surface abnormalities. Herein, we examine these hypothesized links in an exploratory study of joint structural connectivity and cortical surface changes associated with mTBI and its chronic symptoms. Briefly, we consider a cohort of 12 mTBI and 26 control subjects. A set of 588 cortical surface metrics and 4,753 structural connectivity metrics were extracted from cortical surface regions and diffusion weighted magnetic resonance imaging in each subject. Principal component analysis (PCA) was used to reduce the dimensionality of each metric set. We then applied independent component analysis (ICA) both to each PCA space individually and together in a joint ICA approach. We identified a stable independent component across the connectivity-only and joint ICAs which presented significant group differences in subject loadings (p<0.05, corrected). Additionally, we found that two mTBI symptoms, slowed thinking and forgetfulness, were significantly correlated (p<0.05, corrected) with mTBI subject loadings in a surface-only ICA. These surface-only loadings captured an increase in bilateral cortical thickness.
KEYWORDS: Alzheimer's disease, Principal component analysis, Magnetic resonance imaging, Electroencephalography, Neuroimaging, Independent component analysis, Hemodynamics, Functional magnetic resonance imaging, Diffusion, Control systems
Prior neuroimaging studies have demonstrated isolated structural and connectivity changes in the brain due to Alzheimer’s Disease (AD). However, how these changes relate to each other is not well understood. We present a preliminary study to begin to fill this gap by leveraging joint independent component analysis (jICA). We explore how jICA performs in an analysis of T1 and diffusion weighted MRI by characterizing the joint changes of complex cortical surface and structural connectivity metrics in AD in subjects from the Baltimore Longitudinal Study of Aging. We calculate 588 region-based cortical metrics and 4,753 fractional anisotropy-based connectivity metrics and project them into a low-dimensional manifold with principal component analysis. We perform jICA on the manifold and subsequently backproject the independent components to the original data space. We demonstrate component stability with 3-fold cross validation and find differential component loadings between 776 cognitively unimpaired control subjects and 23 with AD that generalizes across folds. In addition, we perform the same analysis on the surface and connectivity metrics separately and find that the joint approach identifies both novel and similar components to the separate approaches. To illustrate the joint approach’s primary utility, we provide an example hypothesis for how surface and connectivity components may vary together with AD. These preliminary results suggest jointly varying independent cortical surface and structural connectivity components can be consistently extracted from MRI data and provide a data-driven way for generating novel hypotheses about AD that may not be captured by separate analyses.
Resting-state functional MRI (rsfMRI) provides important information for studying and mapping the activities and functions of the brain. Conventionally, rsfMRIs are often registered to structural images in the Euclidean space without considering cortical surface geometry. Meanwhile, a surface-based representation offers a relaxed coordinate chart, but this still requires surface registration for group-wise data analysis. In this work, we investigate the performance of two existing surface registration methods in a surface-based rsfMRI analysis framework: FreeSurfer and Hierarchical Spherical Deformation (HSD). To minimize registration bias, we establish shape correspondence using both methods in a groupwise manner that estimates the unbiased average of a given cohort. To evaluate their performance, we focus on neuroanatomical alignment as well as the amount of distortion that can potentially bias surface tessellation for secondary level rsfMRI data analyses. In the pilot analysis, we examine a single timepoint of imaging data from 100 subjects out of an aging cohort. Overall, HSD establishes improved shape correspondence with reduced mean curvature deviation (10.94% less on average per subject, paired t-test: p <10-10) and reduced registration distortion (FreeSurfer: average 41.91% distortion per subject, HSD: 18.63%, paired t-test: p <10-10). Furthermore, HSD introduces less distortion than FreeSurfer in the areas identified in the individual components that were extracted by surface-based independent component analysis (ICA) after spatial smoothing and time series normalization. Consequently, we show that FreeSurfer capture individual components with globally similar but locally different patterns in ICA in visual inspection.
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