Huiqing Dong

Diffusion Tensor Tractography Reveals Disrupted Topological Efficiency in White Matter Structural Networks in Multiple Sclerosis

Little is currently known about the alterations in the topological organization of the white matter (WM) structural networks in patients with multiple sclerosis (MS). In the present study, we used diffusion tensor imaging and deterministic tractography to map the WM structural networks in 39 MS patients and 39 age- and gender-matched healthy controls. Graph theoretical methods were applied to investigate alterations in the network efficiency in these patients. The MS patients and the controls exhibited efficient small-world properties in their WM structural networks. However, the global and local network efficiencies were significantly decreased in the MS patients compared with the controls, with the most pronounced changes observed in the sensorimotor, visual, default-mode, and language areas. Furthermore, the decreased network efficiencies were significantly correlated with the expanded disability status scale scores, the disease durations, and the total WM lesion loads. Together, the results suggest a disrupted integrity in the large-scale brain systems in MS, thus providing new insights into the understanding of MS connectome. Our data also suggest that a topology-based brain network analysis can provide potential biomarkers for disease diagnosis and for monitoring the progression and treatment effects for patients with MS.

Abnormal baseline brain activity in patients with neuromyelitis optica: a resting-state fMRI study.

PURPOSE Recent immunopathologic and MRI findings suggest that tissue damage in neuromyelitis optica (NMO) is not limited to spinal cord and optic nerve, but also in brain. Baseline brain activity can reveal the brain functional changes to the tissue damages and give clues to the pathophysiology of NMO, however, it has never been explored by resting-state functional MRI (fMRI). We used regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI to investigate how baseline brain activity changes in patients with NMO. METHODS Resting-state fMRIs collected from seventeen NMO patients and seventeen age- and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration were further explored. RESULTS Our results showed that NMO patients had significantly decreased ALFF in precuneus, posterior cingulate cortex (PCC) and lingual gyrus; and increased ALFF in middle frontal gyrus, caudate nucleus and thalamus, compared to normal controls. Moderate negative correlations were found between the EDSS and ALFF in the left middle frontal gyrus (r=-0.436, p=0.040) and the left caudate (r=-0.542, p=0.012). CONCLUSION The abnormal baseline brain activity shown by resting-state fMRI in NMO is relevant to cognition, visual and motor systems. It implicates a complex baseline brain status of both functional impairments and adaptations caused by tissue damages in these systems, which gives clues to the pathophysiology of NMO.

Regional homogeneity changes in patients with neuromyelitis optica revealed by resting-state functional MRI

OBJECTIVE Resting-state brain activity in neuromyelitis optica (NMO) patients can give clues to the pathophysiology of the disorder, and may be helpful in diagnosis; however, it has been less explored using functional MRI (fMRI). In the current study, we used a regional homogeneity (ReHo) method to investigate NMO-related modulations of neural activity in the resting state. METHODS Resting-state fMRIs acquired in 17 NMO patients as well as in 17 age- and sex-matched normal controls were compared. Kendalls coefficient of concordance was used to measure the regional homogeneity. Correlative analyses were performed to explore the relationship between the expanded disability status scale (EDSS), disease duration and ReHo in regions with significant group differences. RESULTS Comparing the NMO group with the healthy controls, we found ReHo decreased in extensive brain regions, including the left anterior cingulate, left medial frontal gyrus, left posterior cingulate, right precuneus and right middle temporal gyrus; and increased in the right inferior frontal gyrus. CONCLUSIONS These results demonstrate that neural activity in the resting state is changed in patients with NMO. SIGNIFICANCE The present study reveals clear abnormalities of NMO patients in the baseline activities that have not been well detected, and further improves our understanding of the neural substrates of cognitive impairment in NMO patients.

Differential patterns of spinal cord and brain atrophy in NMO and MS

Objective: To investigate spinal cord and brain atrophy in neuromyelitis optica (NMO), and its relationship with other MRI measurements and clinical disability, compared with patients with multiple sclerosis (MS) and healthy controls (HC). Methods: We recruited 35 patients with NMO, 35 patients with MS, and 35 HC, who underwent both spinal cord and brain MRI. Mean upper cervical cord area (MUCCA), brain parenchymal fraction (BPF), gray matter fraction (GMF), white matter fraction (WMF), and spinal cord and brain lesion loads were measured and compared among groups. Multivariate associations between MUCCA and brain volume measurement and clinical variables were assessed by partial correlations and multiple linear regression. Results: Patients with NMO showed smaller MUCCA than HC (p = 0.004), and patients with MS had a trend of smaller MUCCA compared to HC (p = 0.07), with no significant difference between the patient groups. Patients with NMO showed lower BPF than HC, and patients with MS had lower BPF and GMF than patients with NMO. In NMO, MUCCA was correlated with Expanded Disability Status Scale score (EDSS), number of relapses, and total spinal cord lesion length, while in MS, MUCCA was correlated with WMF and EDSS. MUCCA was the only independent variable for predicting clinical disability measured by EDSS in NMO (R2 = 0.55, p < 0.001) and MS (R2 = 0.17, p = 0.013). Conclusion: NMO showed predominately spinal cord atrophy with mild brain atrophy, while MS demonstrated more brain atrophy, especially in the gray matter. MUCCA is the main MRI-derived parameter for explaining clinical disability in NMO and MS, and may serve as a potential biomarker for further clinical trials, especially in NMO.

Brain plasticity in relapsing–remitting multiple sclerosis: Evidence from resting-state fMRI

The purpose of this study is to investigate whether spontaneous brain activity amplitude alteration occurs in RRMS by comparing appropriately processed fMRI data from subjects with RRMS and healthy controls. Resting-state fMRIs collected from thirty-five RRMS patients and thirty-five age and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration, T2 lesion volume were further explored. Our results showed that RRMS patients showed no regions with decreased ALFF, while showed significantly increased ALFF in the bilateral thalami, right insula (BA 13)/ right superior temporal gyrus (BA 22). The correlation between the EDSS and ALFF in the right insula/ right superior temporal gyrus was significant. From this study, we demonstrate that increased resting state amplitudes occur in the brain of patients with RRMS, specifically in areas with extensive cortical connections. We hypothesize that this is an adaptive phenomenon, reflecting either ongoing cortical plasticity in the resting-state, or increased neuronal activity related to coordination of remapped cortical functions.

Altered Topological Organization of White Matter Structural Networks in Patients with Neuromyelitis Optica

Objective To investigate the topological alterations of the whole-brain white-matter (WM) structural networks in patients with neuromyelitis optica (NMO). Methods The present study involved 26 NMO patients and 26 age- and sex-matched healthy controls. WM structural connectivity in each participant was imaged with diffusion-weighted MRI and represented in terms of a connectivity matrix using deterministic tractography method. Graph theory-based analyses were then performed for the characterization of brain network properties. A multiple linear regression analysis was performed on each network metric between the NMO and control groups. Results The NMO patients exhibited abnormal small-world network properties, as indicated by increased normalized characteristic path length, increased normalized clustering and increased small-worldness. Furthermore, largely similar hub distributions of the WM structural networks were observed between NMO patients and healthy controls. However, regional efficiency in several brain areas of NMO patients was significantly reduced, which were mainly distributed in the default-mode, sensorimotor and visual systems. Furthermore, we have observed increased regional efficiency in a few brain regions such as the orbital parts of the superior and middle frontal and fusiform gyri. Conclusion Although the NMO patients in this study had no discernible white matter T2 lesions in the brain, we hypothesize that the disrupted topological organization of WM networks provides additional evidence for subtle, widespread cerebral WM pathology in NMO.

Cortical thinning correlates with cognitive change in multiple sclerosis but not in neuromyelitis optica.

AbstractObjectivesTo compare spatial patterns of cortical thickness alterations in neuromyelitis optica (NMO) and multiple sclerosis (MS); and to investigate the correlations between cortical thinning and clinical variables in NMO and MS.MethodsWe studied 23 patients with NMO, 27 patients with MS and 26 healthy controls (HCs). The global, brain region and vertex-based cortical thickness (CTh) were analysed and compared among the three groups. A general linear model was used to investigate the correlations between cortical thinning and clinical measures.ResultsA limited number of cortical regions in visual cortex were found to be significantly thinner in NMO patients than in HCs. The MS patients exhibited more widespread cortical thinning compared with HCs, and significantly greater cortical thinning in the insula and the parahippocampus compared with NMO. The extent of cortical thinning in several brain regions correlated with cognitive measures in MS, but not in NMO.ConclusionsNeocortical thinning in NMO mainly affects visual cortex, while MS patients show much more extensive cortical thinning. Cognitive changes are correlated with cortical atrophy in MS not in NMO. The substrates of cognitive changes in MS and NMO could therefore be different.Key Points• MS patients show much more extensive cortical thinning than NMO. • Cortical thinning of insula and parahippocampus particularly distinguishes MS from NMO. • Cognitive changes are correlated with cortical atrophy in MS but not in NMO.

Baseline brain activity changes in patients with clinically isolated syndrome revealed by resting-state functional MRI

Background A clinically isolated syndrome (CIS) is the first manifestation of multiple sclerosis (MS). Previous task-related functional MRI studies demonstrate functional reorganization in patients with CIS. Purpose To assess baseline brain activity changes in patients with CIS by using the technique of regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI. Material and Methods Resting-state fMRIs data acquired from 37 patients with CIS and 37 age- and sex-matched normal controls were compared to investigate ALFF differences. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration, and T2 lesion volume (T2LV) were further explored. Results Patients with CIS had significantly decreased ALFF in the right anterior cingulate cortex, right caudate, right lingual gyrus, and right cuneus (P < 0.05 corrected for multiple comparisons using Monte Carlo simulation) compared to normal controls, while no significantly increased ALFF were observed in CIS. No significant correlation was found between the EDSS, disease duration, T2LV, and ALFF in regions with significant group differences. Conclusion In patients with CIS, resting-state fMRI demonstrates decreased activity in several brain regions. These results are in contrast to patients with established MS, in whom ALFF demonstrates several regions of increased activity. It is possible that this shift from decreased activity in CIS to increased activity in MS could reflect the dynamics of cortical reorganization.

Disrupted topological organization of structural and functional brain connectomes in clinically isolated syndrome and multiple sclerosis

The brain connectome of multiple sclerosis (MS) has been investigated by several previous studies; however, it is still unknown how the network changes in clinically isolated syndrome (CIS), the earliest stage of MS, and how network alterations on a functional level relate to the structural level in MS disease. Here, we investigated the topological alterations of both the structural and functional connectomes in 41 CIS and 32 MS patients, compared to 35 healthy controls, by combining diffusion tensor imaging and resting-state functional MRI with graph analysis approaches. We found that the structural connectome showed a deviation from the optimal pattern as early as the CIS stage, while the functional connectome only showed local changes in MS patients, not in CIS. When comparing two patient groups, the changes appear more severe in MS. Importantly, the disruptions of structural and functional connectomes in patients occurred in the same direction and locally correlated in sensorimotor component. Finally, the extent of structural network changes was correlated with several clinical variables in MS patients. Together, the results suggested early disruption of the structural brain connectome in CIS patients and provided a new perspective for investigating the relationship of the structural and functional alterations in MS.

White matter atrophy in brain of neuromyelitis optica: a voxel-based morphometry study.

Background Recent studies have shown that tissue damage in neuromyelitis optica (NMO) is not limited to the spinal cord and optic nerve but can also appear in the brain. Previous magnetic resonance imaging (MRI) studies have reported controversial findings regarding the presence of white matter atrophy in NMO patients. Purpose To investigate regional white matter changes in NMO using voxel-based morphometry (VBM). Material and Methods Conventional MRI and T1-weighted three-dimensional MRI were performed on 20 patients with NMO and 20 age- and sex-matched normal controls (NCs). The data were analyzed by statistical parametric mapping 5 (SPM5) to generate white matter concentration maps, and regional white matter concentrations were compared between the two groups. Relationships between the white matter concentration in regions with significant group differences and the Expanded Disability Status Scale (EDSS) and disease duration were further explored. Results Compared to NCs, NMO patients had decreased white matter volumes in the right precentral gyrus, right postcentral gyrus, left middle and medial frontal gyrus, right superior frontal gyrus, bilateral inferior and superior parietal lobule, right angular gyrus, right middle occipital gyrus, and left precuneus. No significant correlation was found between white matter regions with volume reduction and the EDSS and disease duration in NMO. Conclusion We found white matter atrophy in several brain regions in the frontal, parietal, and occipital lobes in NMO, suggesting that subtle white matter damage relevant to the motor, vision, and cognition systems exists in NMO patients. The pattern of white matter atrophy in NMO is different from that in multiple sclerosis (MS).