Objectively measured sedentary behavior and brain volumetric measurements in multiple sclerosis.

AIM: This study examined the association between sedentary behavior patterns and whole brain gray matter (GM), white matter (WM) and subcortical GM structures in persons with multiple sclerosis (MS). METHODS: 36 persons with MS wore an accelerometer and underwent a brain MRI. Whole brain GM and WM and deep GM structures were calculated from 3D T1-weighted structural brain images. RESULTS: There were statistically significant (p < 0.01) and moderate or large associations between number of sedentary bouts/day and brain volume measures. The primary result was a consistent negative association between number of sedentary bouts/day and whole brain GM and WM, and deep GM structures. CONCLUSION: We provide novel evidence for decreased brain volume as a correlate of a sedentary behavior pattern in persons with MS.

Diffusion tensor imaging of the corticospinal tract and walking performance in multiple sclerosis.

Research has identified a significant relationship between DTI (Diffusion Tensor Imaging) indices in the Corticospinal Tract (CST) and disability status in persons with multiple sclerosis (MS). To date, there is little known about the association between DTI indices of the CST with walking and gait outcomes in MS. This study examined the associations among DTI indices [fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD)] of the CST with walking and gait outcomes in persons with MS. We enrolled 69 persons with MS who underwent 3T brain magnetic resonance imaging (MRI) and examined white matter structural integrity in the CST in the brain with DTI. Participants completed three walking performance assessments: 6-minute walk (6MW), timed 25-foot walk (T25FW), and gait testing. We examined associations using Spearman (r(s)) and partial Spearman correlation (pr(s)) analyses, using the entire sample and stratifying by disability status after controlling for age and sex. After controlling for age, sex, and disease duration, RD was significantly correlated (p<0.05) with step time (pr(s)=0.30). AD was significantly correlated (p<0.05) with step length (pr(s)=-0.32). MD was significantly associated (p<0.05) with 6MW (pr(s)=-0.35), T25FW (pr(s)=-0.34), gait velocity (pr(s)=-0.31), step time (pr(s)=0.29), and step length (pr(s)=-0.36). FA was not significantly correlated with any of the walking parameters (p>0.05). We provide novel evidence of possible motor pathway damage involved in walking performance in MS. There may be subtle differences in associations between MD, AD, and RD with walking outcomes, and these could be assessed in future longitudinal examinations and clinical trials of motor rehabilitation.

Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors.

Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment.

Fully automated open-source lesion mapping of T2-FLAIR images with FSL correlates with clinical disability in MS.

BACKGROUND: T2 Lesion Volume (T2LV) has been an important biomarker for multiple sclerosis (MS). Current methods available to quantify lesions from MR images generally require manual adjustments or multiple images with different contrasts. Further, implementations are often not easily or openly accessible. OBJECTIVE: We created a fully unsupervised, single T2 FLAIR image T2LV quantification package based on the popular open-source imaging toolkit FSL. METHODS: By scripting various processing tools in FSL, we developed an image processing pipeline that distinguishes normal brain tissue from CSF and lesions. We validated our method by hierarchical multiple regression (HMR) with a preliminary study to see if our T2LVs correlate with clinical disability measures in MS when controlled for other variables. RESULTS: Pearson correlations between T2LV and Expanded Disability Status Scale (EDSS: r = 0.344, P = 0.013), Six-Minute Walk (6MW: r = -0.513, P = 0.000), Timed 25-Foot Walk (T25FW: r = -0.438, P = .000), and Symbol Digit Modalities Test (SDMT: r = -0.499, P = 0.000) were all significant. Partial correlations controlling for age were significant between T2LV and 6MW (r = -0.433, P = 0.002), T25FW (r = -0.392, P = 0.004), and SDMT (r = -0.450, P = 0.001). In HMR, T2LV explained significant additional variance in 6MW (R(2) change = 0.082, P = 0.020), after controlling for confounding variables such as age, white matter volume (WMV), and gray matter volume (GMV). CONCLUSION: Our T2LV quantification software produces T2LVs from a single FLAIR image that correlate with physical disability in MS and is freely available as open-source software.

Objectively Measured Physical Activity Is Associated with Brain Volumetric Measurements in Multiple Sclerosis.

BACKGROUND: Little is known about physical activity and its association with volumes of whole brain gray matter and white matter and deep gray matter structures in persons with multiple sclerosis (MS). PURPOSE: This study examined the association between levels of physical activity and brain volumetric measures from magnetic resonance imaging (MRI) in MS. METHOD: 39 persons with MS wore an accelerometer for a 7-day period and underwent a brain MRI. Normalized GM volume (NGMV), normalized WM volume (NWMV), and deep GM structures were calculated from 3D T1-weighted structural brain images. We conducted partial correlations (pr) controlling for demographic and clinical variables. RESULTS: Moderate-to-vigorous physical activity (MVPA) was significantly associated with NGMV (pr = 0.370, p < 0.05), NWMV (pr = 0.433, p < 0.01), hippocampus (pr = 0.499, p < 0.01), thalamus (pr = 0.380, p < 0.05), caudate (pr = 0.539, p < 0.01), putamen (pr = 0.369, p < 0.05), and pallidum (pr = 0.498, p < 0.01) volumes, when controlling for sex, age, clinical course of MS, and Expanded Disability Status Scale score. There were no associations between sedentary and light physical activity with MRI outcomes. CONCLUSION: Our results provide the first evidence that MVPA is associated with volumes of whole brain GM and WM and deep GM structures that are involved in motor and cognitive functions in MS.

Pallidal and caudate volumes correlate with walking function in multiple sclerosis.

BACKGROUND: Walking dysfunction is common in multiple sclerosis (MS). The thalamus and basal ganglia seemingly have important associations with walking performance. The contribution of these subcortical gray matter (SGM) structures for walking dysfunction is poorly understood in MS. PURPOSE: This study examined associations among volumes of the thalamus and basal ganglia with walking outcomes in MS. METHOD: We enrolled 61 MS patients who underwent brain MRI and completed the 6-minute walk (6MW) and timed 25-foot walk (T25FW). Volumes of the thalamus, caudate, putamen, and pallidum as well as whole-brain white matter (WM) and gray matter (GM) were calculated from 3D T1-weighted structural brain images. We examined associations using bivariate correlations (r) and partial correlations (pr) that controlled for age, MS clinical course, and whole-brain WM and GM volumes. We further performed hierarchical linear regression (HLR) for identifying the strongest SGM correlate of walking performance. RESULTS: The 6MW and T25FW correlated significantly with volumes of the thalamus (r's=.382 & .383), caudate (r's=.388 & .416), pallidum (r's=.457 & .457), and putamen (r's=.258 & .293) in bivariate correlations. The 6MW and T25FW remained significantly correlated with caudate (pr's=.243 & .312) and pallidum (pr's=.321 & .345) volumes in partial correlations. Pallidum volume was the strongest SGM correlate of 6MW (ß=.39) and T25FW (ß=.40) performance in HLR. CONCLUSION: We provide novel evidence of possible SGM structures, particularly the pallidum and perhaps caudate, as correlates of walking performance in MS.

Cardiorespiratory fitness and its association with thalamic, hippocampal, and basal ganglia volumes in multiple sclerosis.

BACKGROUND: There is little known about cardiorespiratory fitness and its association with volumes of the thalamus, hippocampus, and basal ganglia in multiple sclerosis (MS). Such inquiry is important for identifying a possible behavioral approach (e.g., aerobic exercise training) that might change volumes of deep gray matter (DGM) structures associated with cognitive and motor functions in MS. PURPOSE: This study examined the association between cardiorespiratory fitness and volumes of the thalamus, hippocampus, and basal ganglia in MS. METHOD: We enrolled 35 persons with MS who underwent a maximal exercise test for measuring cardiorespiratory fitness as peak oxygen consumption (VO2peak) and brain MRI. Volumes of the thalamus, hippocampus, caudate, putamen, and pallidum were calculated from 3D T1-weighted structural brain images. We examined associations using partial (pr) correlations controlling for demographic and clinical variables. RESULTS: VO2peak was significantly associated with composite scaled volumes of the caudate(pr = .47, p < .01), putamen (pr = .44, p < .05), pallidum (pr = .40, p < .05), and hippocampus (pr = .42, p < .05), but not thalamus (pr = .31, p = .09), when controlling for sex, age, disability, and duration of MS. CONCLUSION: Our results provide novel evidence that cardiorespiratory fitness is associated with volumes of DGM structures that are involved in motor and cognitive functions in MS.