In recent years, research on network analysis applied to MRI data has advanced significantly. However, the majority of the studies are limited to single networks obtained from resting-state fMRI, diffusion MRI, or grey matter probability maps derived from T1 images. Although a limited number of previous studies have combined two of these networks, none have introduced a framework to combine morphological, structural and functional brain connectivity networks. The aim of this study was to combine the morphological, structural and functional information, thus defining a new multilayer network perspective. This has proved advantageous when jointly analysing multiple types of relational data from the same objects simultaneously using graph-mining techniques. The main contribution of this research is the design, development and validation of a framework that merges these three layers of information into one multilayer network that links and relates the integrity of white matter connections with grey matter probability maps and resting-state fMRI. To validate our framework, several metrics from graph theory are expanded and adapted to our specific domain characteristics. This proof of concept was applied to a cohort of people with MS, and results show that several brain regions with a synchronised connectivity deterioration could be identified.
The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients with the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), and Symbol Digit Modalities Test (SDMT) at two time-points. We used machine learning to analyse the predictive value of baseline WM fractional anisotropy and GM mean diffusivity, and to identify areas related to each outcome at 4.1 years follow-up. Motor performance was associated with WM (T25FW: RMSE = 0.524, R2 = 0.304; 9HPT dominant hand: RMSE = 0.662, R2 = 0.062; 9HPT non-dominant hand: RMSE = 0.649, R2 = 0.139), and SDMT with GM diffusion metrics (RMSE = 0.772, R2 = 0.186). Cingulum, longitudinal fasciculus, optic radiation, forceps minor and frontal aslant were the WM tracts most closely linked to motor dysfunction, and temporal and frontal cortex were relevant for cognition. Regional specificity related to clinical outcomes provide valuable information that can be used to develop more accurate predictive models that could improve therapeutic strategies.
BackgroundWe aimed to describe the severity of the changes in brain diffusion-based connectivity as multiple sclerosis (MS) progresses and the microstructural characteristics of these networks that are associated with distinct MS phenotypes.MethodsClinical information and brain MRIs were collected from 221 healthy individuals and 823 people with MS at 8 MAGNIMS centres. The patients were divided into four clinical phenotypes: clinically isolated syndrome, relapsing-remitting, secondary progressive and primary progressive. Advanced tractography methods were used to obtain connectivity matrices. Then, differences in whole-brain and nodal graph-derived measures, and in the fractional anisotropy of connections between groups were analysed. Support vector machine algorithms were used to classify groups.ResultsClinically isolated syndrome and relapsing-remitting patients shared similar network changes relative to controls. However, most global and local network properties differed in secondary progressive patients compared with the other groups, with lower fractional anisotropy in most connections. Primary progressive participants had fewer differences in global and local graph measures compared with clinically isolated syndrome and relapsing-remitting patients, and reductions in fractional anisotropy were only evident for a few connections. The accuracy of support vector machine to discriminate patients from healthy controls based on connection was 81%, and ranged between 64% and 74% in distinguishing among the clinical phenotypes.ConclusionsIn conclusion, brain connectivity is disrupted in MS and has differential patterns according to the phenotype. Secondary progressive is associated with more widespread changes in connectivity. Additionally, classification tasks can distinguish between MS types, with subcortical connections being the most important factor.
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