1,720,985 research outputs found
Two-year regional grey and white matter volume changes with natalizumab and fingolimod
No full textTo compare the efficacy of fingolimod and natalizumab in preventing regional grey matter (GM) and white matter (WM) atrophy in relapsing-remitting multiple sclerosis (RRMS) over 2 years
Multi-branch convolutional neural network for multiple sclerosis lesion segmentation
Full text linkIn this paper, we present an automated approach for segmenting multiple sclerosis (MS) lesions from multi-modal brain magnetic resonance images. Our method is based on a deep end-to-end 2D convolutional neural network (CNN) for slice-based segmentation of 3D volumetric data. The proposed CNN includes a multi-branch downsampling path, which enables the network to encode information from multiple modalities separately. Multi-scale feature fusion blocks are proposed to combine feature maps from different modalities at different stages of the network. Then, multi-scale feature upsampling blocks are introduced to upsize combined feature maps to leverage information from lesion shape and location. We trained and tested the proposed model using orthogonal plane orientations of each 3D modality to exploit the contextual information in all directions. The proposed pipeline is evaluated on two different datasets: a private dataset including 37 MS patients and a publicly available dataset known as the ISBI 2015 longitudinal MS lesion segmentation challenge dataset, consisting of 14 MS patients. Considering the ISBI challenge, at the time of submission, our method was amongst the top performing solutions. On the private dataset, using the same array of performance metrics as in the ISBI challenge, the proposed approach shows high improvements in MS lesion segmentation compared with other publicly available tools
The insula modulates the effects of aerobic training on cardiovascular function and ambulation in multiple sclerosis
No full textBACKGROUND: Impairment of cardiovascular control is common in multiple sclerosis (MS), possibly due to damage of strategic brain regions such as the insula. Aerobic training (AT) targets cardiopulmonary system and may represent a neuroprotective strategy. PURPOSE: To investigate whether insular damage (T2-hyperintense lesions and volume) is associated with cardiovascular fitness (CF) and influences AT effects in MS. METHODS: Sixty-one MS patients were randomized to an AT intervention group (MS-AT) and a motor training control group (MS-C). At baseline and after training (24 sessions over 2–3 months), peak of oxygen consumption (VO2max), heart rate reserve (HRR), 6-min walk test (6MWT) and whole brain and insula MRI data were collected. Two healthy control (HC) groups were enrolled for CF and MRI data analysis. RESULTS: At baseline, MS patients vs HC showed impaired VO2max, HRR and 6MWT (p < 0.001) and widespread gray matter atrophy, including bilateral insula. In MS patients, left insula T2-lesion volume correlated with HRR (r = 0.27, p = 0.042). After training, MS-AT, especially those without insular T2-hyperintense lesions, showed 6MWT improvement (p < 0.05) and a stable insular volume, whereas MS-C showed left insular volume loss (p < 0.001). CONCLUSIONS: By increasing 6MWT performance, our results suggest that AT may improve walking capacity and submaximal measure of CF in MS patients. Such beneficial effect may be modulated by insula integrity
Advanced diffusion-weighted imaging models better characterize white matter neurodegeneration and clinical outcomes in multiple sclerosis
No full textBackground White matter (WM) atrophy is relevant in multiple sclerosis (MS), but the methods of analysis currently used are not specific for microstructural changes. The aims of this study were to assess the use of advanced diffusion-weighted imaging (DWI) techniques proposed as measures of baseline and longitudinal WM atrophy in MS and to analyze whether these measures helped explain MS clinical disability (including cognitive impairment) better than volumetric and diffusion tensor (DT)-derived measures. Methods 3DT1-weighted and DWI sequences were applied to 86 MS and 55 healthy controls (HC) at baseline and after one-year. Intra-cellular volume (v(ic)) maps were computed from neurite orientation dispersion and density imaging model. Voxel-wise fiber-bundle cross-section (FCS) atrophy in MS compared to HC was estimated. Maps of fractional anisotropy and mean diffusivity were also obtained from DWI for a comparison with the proposed advanced DW-derived measures (v(ic) and FCS). Results Both at baseline and after 1-year, only FCS measure showed a significant atrophy in relapsing-remitting (RR) MS compared to HC and in progressive MS compared to RRMS, mainly located in specific WM tracts (corticospinal tract, splenium of the corpus callosum, left optic radiation, bilateral cingulum, middle cerebellar peduncle and anterior commissure, p value < 0.05). Global baseline FCS and v(ic) were the selected predictors of clinical (R-sq = 0.33, p = 0.007) and cognitive scores (R-sq = 0.29, p = 0.0014) in a linear regression model. Conclusion Voxel-based FCS was able to detect WM tracts atrophy in MS clinical phenotypes with greater anatomical specificity compared to other measures (volumetric and DT-derived measures of WM damage). FCS and v(ic) measured at baseline in the WM were the best predictors of clinical disability and cognitive impairment
Glymphatic System May Mediate the Relation Between Choroid Plexus and Brain Damage in Multiple Sclerosis
No full textBackground and objectives: The choroid plexus (CP) regulates immune functions and produces most CSF that circulates in the brain parenchyma through perivascular spaces, part of the glymphatic system. In multiple sclerosis (MS), CP enlargement and glymphatic dysfunction are associated with inflammatory activity, clinical disability, and brain damage, but their interrelation is unclear. We investigated whether glymphatic system dysfunction mediates the association between CP enlargement and brain damage in patients with MS. Methods: Brain fluid-attenuated inversion recovery, 3-dimensional T1-weighted, diffusion-weighted, and susceptibility-weighted sequences were obtained from 146 patients with MS and 72 healthy controls (HC). Glymphatic function was assessed using the diffusion along the perivascular space (DTI-ALPS) index, and CP volume was measured automatically. Results: Patients with MS showed significantly higher white matter (WM) lesion and CP volumes (p < 0.001), and lower DTI-ALPS index, brain, WM, thalamic, and cortical volumes than HC (p ≤ 0.048). In patients with MS, higher CP volume correlated with a lower DTI-ALPS index (r = -0.305, false discovery rate p value = 0.001). Both measures were associated with higher total, periventricular, and juxtacortical (JC) WM lesion volumes (CP volume: r from 0.285 to 0.340, p-FDR ≤ 0.001; DTI-ALPS index: r from -0.301 to -0.444, p ≤ 0.001), and lower brain, thalamic, cortical, and WM volumes (CP volume: r from -0.246 to -0.405, p-FDR ≤ 0.006; DTI-ALPS index: from 0.269 to 0.497, p-FDR ≤ 0.003). The DTI-ALPS index partially mediated the associations of normalized choroid plexus volume with total, periventricular, and JC T2-hyperintense WM lesion volumes (standardized-β ranging from 0.073 to 0.115, relative effect ranging from 25.2% to 33.6%) and normalized brain, thalamic, cortical, and WM volumes (standardized-β ranging from -0.086 to -0.125, relative effect ranging from 25.3% to 52.7%). Discussion: In MS, enlarged normalized CP volume may contribute to brain damage accumulation possibly through the promotion of a chronic proinflammatory state and the mediation of glymphatic system dysfunction
Quantification of Thalamic Atrophy in MS: From the Multicenter Italian Neuroimaging Network Initiative Data Set to Clinical Application
No full textBACKGROUND AND PURPOSE: Thalamic atrophy occurs from the earliest phases of MS; however, this measure is not included in clinical practice. Our purpose was to obtain a reliable segmentation of the thalamus in MS by comparing existing automatic methods cross-sectionally and longitudinally.MATERIALS AND METHODS: MR images of 141 patients with relapsing-remitting MS (mean age, 38 years; range, 19-58 years; 95 women) and 69 healthy controls (mean age, 36 years; range, 22-69 years; 47 women) were retrieved from the Italian Neuroimaging Network Initiative repository: T1WI, T2WI, and DWI at baseline and after 1 year (136 patients, 31 healthy controls). Three segmentation software programs (FSL-FIRST, FSL-MIST, FreeSurfer) were compared. At baseline, agreement among pipelines, correlations with age, disease duration, clinical score, and T2-hyperintense lesion volume were evaluated. Effect sizes in differentiating patients and controls were assessed cross-sectionally and longitudinally. Variability of longitudinal changes in controls and sample sizes were assessed. False discovery rate-adjusted P <.05 was considered significant.RESULTS: At baseline, FSL-FIRST and FSL-MIST showed the highest agreement in the results of thalamic volume (R = 0.87, P <.001), with the highest effect size for FSL-MIST (Cohen d = 1.11); correlations with demographic and clinical variables were comparable for all software. Longitudinally, FSL-MIST showed the lowest variability in estimating thalamic volume changes for healthy controls (SD= 1.07%), the highest effect size (Cohen d = 0.44), and the smallest sample size at 80% power level (15 subjects per group).CONCLUSIONS: Multimodal segmentation by FSL-MIST increased the robustness of the results with better capability to detect small variations in thalamic volumes
Cerebrospinal Fluid-In Gradient of Cortical and Deep Gray Matter Damage in Multiple Sclerosis
No full textBackground and ObjectivesA CSF-in gradient in cortical and thalamic gray matter (GM) damage has been found in multiple sclerosis (MS). We concomitantly explored the patterns of cortical, thalamic, and caudate microstructural abnormalities at progressive distances from CSF using a multiparametric MRI approach.MethodsFor this cross-sectional study, from 3T 3D T1-weighted scans, we sampled cortical layers at 25%-50%-75% depths from pial surface and thalamic and caudate bands at 2-3-4 voxels from the ventricular-GM interface. Using linear mixed models, we tested between-group comparisons of magnetization transfer ratio (MTR) and R2* layer-specific z-scores, CSF-in across-layer z-score changes, and their correlations with clinical (disease duration and disability) and structural (focal lesions, brain, and choroid plexus volume) MRI measures.ResultsWe enrolled 52 patients with MS (33 relapsing-remitting [RRMS], 19 progressive [PMS], mean age: 46.4 years, median disease duration: 15.1 years, median: EDSS 2.0) and 70 controls (mean age 41.5 ± 12.8). Compared with controls, RRMS showed lower MTR values in the outer and middle cortical layers (false-discovery rate [FDR]-p ≤ 0.025) and lower R2* values in all 3 cortical layers (FDR-p ≤ 0.016). PMS had lower MTR values in the outer and middle cortical (FDR-p ≤ 0.016) and thalamic (FDR-p ≤ 0.048) layers, and in the outer caudate layer (FDR-p = 0.024). They showed lower R2* values in the outer cortical layer (FDR-p = 0.003) and in the outer thalamic layer (FDR-p = 0.046) and higher R2* values in all 3 caudate layers (FDR-p ≤ 0.031). Both RRMS and PMS had a gradient of damage, with lower values closer to the CSF, for cortical (FDR-p ≤ 0.002) and thalamic (FDR-p ≤ 0.042) MTR. PMS showed a gradient of damage for cortical R2* (FDR-p = 0.005), thalamic R2* (FDR-p = 0.004), and caudate MTR (FDR-p ≤ 0.013). Lower MTR and R2* of outer cortical, thalamic, and caudate layers and steeper gradient of damage toward the CSF were significantly associated with older age, higher T2-hyperintense white matter lesion volume, higher thalamic lesion volume, and lower brain volume (β ≥ 0.08, all FDR-p ≤ 0.040). Lower MTR of outer caudate layer was associated with more severe disability (β = -0.26, FDR-p = 0.040). No correlations with choroid plexus volume were found.DiscussionCSF-in damage gradients are heterogeneous among different GM regions and through MS course, possibly reflecting different dynamics of demyelination and iron loss/accumulation
Spatial correspondence among regional gene expressions and gray matter volume loss in multiple sclerosis
No full textIn multiple sclerosis (MS), a non-random and clinically relevant pattern of gray matter (GM) volume loss has been described. Whether differences in regional gene expression might underlay distinctive pathological processes contributing to this regional variability has not been explored yet. Two hundred eighty-six MS patients and 172 healthy controls (HC) underwent a brain 3T MRI, a complete neurological evaluation and a neuropsychological assessment. Using Allen Human Brain Atlas, voxel-based morphometry and MENGA platform, we integrated brain transcriptome and neuroimaging data to explore the spatial cross-correlations between regional GM volume loss and expressions of 2710 genes involved in MS (p < 0.05, family-wise error-corrected). Enrichment analyses were performed to evaluate overrepresented molecular functions, biological processes and cellular components involving genes significantly associated with voxel-based morphometry-derived GM maps (p < 0.05, Bonferroni-corrected). A diffuse GM volume loss was found in MS patients compared to HC and it was spatially correlated with 74 genes involved in GABA neurotransmission and mitochondrial oxidoreductase activity mainly expressed in neurons and astrocytes. A more severe GM volume loss was spatially associated, in more disabled MS patients, with 44 genes involved in mitochondrial integrity of all resident cells of the central nervous system (CNS) and, in cognitively impaired MS patients, with 64 genes involved in mitochondrial protein heterodimerization and oxidoreductase activities expressed also in microglia and endothelial cells. Specific differences in the expressions of genes involved in synaptic GABA receptor activities and mitochondrial functions in resident CNS cells may influence regional susceptibility to MS-related excitatory/inhibitory imbalance and oxidative stress, and subsequently, to GM volume loss
A Fully Automatic Method to Segment Choroid Plexuses in Multiple Sclerosis Using Conventional MRI Sequences
Full text linkBackground: Choroid plexus (CP) volume has been recently proposed as a proxy for brain neuroinflammation in multiple sclerosis (MS).Purpose: To develop and validate a fast automatic method to segment CP using routinely acquired brain T1-weighted and FLAIR MRI.Study Type: Retrospective.Population: Fifty-five MS patients (33 relapsing-remitting, 22 progressive; mean age = 46.8 +/- 10.2 years; 31 women) and 60 healthy controls (HC; mean age = 36.1 +/- 12.6 years, 33 women).Field Strength/Sequence: 3D T2-weighted FLAIR and 3D T1-weighted gradient echo sequences at 3.0 T.Assessment: Brain tissues were segmented on T1-weighted sequences and a Gaussian Mixture Model (GMM) was fitted to FLAIR image intensities obtained from the ventricle masks of the SIENAX. A second GMM was then applied on the thresholded and filtered ventricle mask. CP volumes were automatically determined and compared with those from manual segmentation by two raters (with 3 and 10 years' experience; reference standard). CP volumes from previously published automatic segmentation methods (freely available Freesurfer [FS] and FS-GMM) were also compared with reference standard. Expanded Disability Status Scale (EDSS) score was assessed within 3 days of MRI. Computational time was assessed for each automatic technique and manual segmentation.Statistical Tests: Comparisons of CP volumes with reference standard were evaluated with Bland Altman analysis. Dice similarity coefficients (DSC) were computed to assess automatic CP segmentations. Volume differences between MS and HC for each method were assessed with t-tests and correlations of CP volumes with EDSS were assessed with Pearson's correlation coefficients (R). A P value <0.05 was considered statistically significant.Results: Compared to manual segmentation, the proposed method had the highest segmentation accuracy (mean DSC = 0.65 +/- 0.06) compared to FS (mean DSC = 0.37 +/- 0.08) and FS-GMM (0.58 +/- 0.06). The percentage CP volume differences relative to manual segmentation were -0.1% +/- 0.23, 4.6% +/- 2.5, and -0.48% +/- 2 for the proposed method, FS, and FS-GMM, respectively. The Pearson's correlations between automatically obtained CP volumes and the manually obtained volumes were 0.70, 0.54, and 0.56 for the proposed method, FS, and FS-GMM, respectively. A significant correlation between CP volume and EDSS was found for the proposed automatic pipeline (R = 0.2), for FS-GMM (R = 0.3) and for manual segmentation (R = 0.4). Computational time for the proposed method (32 +/- 2 minutes) was similar to the manual segmentation (20 +/- 5 minutes) but <25% of the FS (120 +/- 15 minutes) and FS-GMM (125 +/- 15 minutes) methods.Data Conclusion: This study developed an accurate and easily implementable method for automatic CP segmentation in MS using T1-weighted and FLAIR MRI
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