Voxel-wise Tract-based Spatial Statistics Research Articles

Alterations in white matter microstructures and cognitive dysfunctions in benign childhood epilepsy with centrotemporal spikes

Although benign childhood epilepsy with centrotemporal spikes (BECTS) is known to have good prognosis, patients often manifest neuropsychological impairments. This study aimed to investigate cognitive dysfunctions and their relationship with white matter microstructural changes in BECTS patients. Nineteen BECTS and 25 normal subjects aged 7-16 years were included. Neuropsychological performances were assessed by the Wechsler Intelligence Scale for Children III, executive function tests, verbal and visuospatial memory tests, the verbal fluency and Boston naming tests. Diffusion tensor imaging (DTI) was performed to measure the fractional anisotropy (FA), axial (AD), radial (RD), and mean diffusivities (MD). The voxel-wise tract-based spatial statistics and region of interest methods were used for DTI, and their correlations with cognitive variables were analyzed. Patients with BECTS had lower intelligence quotient (IQ) scores compared with those of the control group. Higher AD and MD values were found in the left superior longitudinal fasciculus, the retrolenticular part of the internal capsule, posterior thalamic radiation, sagittal stratum and the body of the corpus callosum in BECTS patients compared with controls. Lower performances in verbal IQ, freedom from distractibility and processing speed were correlated with higher AD in the left superior fronto-occipital fasciculus, and lower verbal IQ scores were correlated with decreased FA values in the splenium of the corpus callosum in these patients. White matter microstructural changes predominantly in the left hemisphere might contribute to their cognitive abnormalities especially verbal IQ in BECTS patients.

Reduced White Matter Integrity in Sibling Pairs Discordant for Bipolar Disorder

Several lines of evidence indicate that white matter integrity is compromised in bipolar disorder, but the nature, extent, and biological causes remain elusive. To determine the extent to which white matter deficits in bipolar disorder are familial, the authors investigated white matter integrity in a large sample of bipolar patients, unaffected siblings, and healthy comparison subjects. The authors collected diffusion imaging data for 64 adult bipolar patients, 60 unaffected siblings (including 54 discordant sibling pairs), and 46 demographically matched comparison subjects. Fractional anisotropy was compared between the groups using voxel-wise tract-based spatial statistics and by extracting mean fractional anisotropy from 10 regions of interest. Additionally, intraclass correlation coefficients were calculated between the sibling pairs as an index of familiality. Widespread fractional anisotropy reductions in bipolar patients (>40,000 voxels) and more subtle reductions in their siblings, mainly restricted to the corpus callosum, posterior thalamic radiations, and left superior longitudinal fasciculus (>2,000 voxels) were observed. Similarly, region-of-interest analysis revealed significant reductions in most white matter regions in patients. In siblings, fractional anisotropy in the posterior thalamic radiation and the forceps was nominally reduced. Significant between-sibling correlations were found for mean fractional anisotropy across the tract-based spatial statistic skeleton, within significant clusters, and within nearly all regions of interest. These findings emphasize the relevance of white matter to neuropathology and familiality of bipolar disorder and encourage further use of white matter integrity markers as endophenotypes in genetic studies.

Combining Whole-Brain Voxel-Wise Analysis with In Vivo Tractography of Diffusion Behavior after Sports-Related Concussion in Adolescents: A Preliminary Report

We have previously shown that sports-related concussion in adolescents is associated with changes in whole-brain properties of white-matter pathways. Here, we assess local changes within these pathways. Twelve adolescents with a clinical diagnosis of subacute concussion and 10 healthy adolescents matched for age, gender, and physical activity completed magnetic resonance imaging scanning. Voxel-wise tract-based spatial statistics and tractography were performed to assess local changes in diffusion-based measures of microstructural properties of white-matter pathways (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) between the two groups. Fractional anisotropy values were higher for the concussed group in multiple cluster regions using tract-based spatial statistics, primarily in frontal white-matter regions, including the anterior corona radiata bilaterally. Using these regions of altered diffusion characteristics to seed fiber tractography, significantly reduced axial diffusivity in tracts passing through these areas were detected in the concussed group (p=0.04). A trend toward reduced mean and radial diffusivity in the concussed group was also observed within the same reconstructed tracts. Diffusion behavior within these tracts was significantly correlated with an assessment of concussion status (Sports Concussion Assessment Tool 2). Fractional anisotropy within the reconstructed tracts was not significantly different between the two groups. These results suggest that subacute concussion in adolescents is associated with altered diffusion properties within regional white-matter tissue and along reconstructed fiber pathways. Combining voxel-wise analysis with fiber tractography provides an alternative objective approach to evaluate and identify subtle changes in white-matter fiber integrity after concussion.

Cerebral Diffusion Tensor MR Tractography in Tuberous Sclerosis Complex: Correlation with Neurologic Severity and Tract-Based Spatial Statistical Analysis

The neurologic significance of residual cerebral white matter tracts, identified on diffusion tensor tractography, has not been well studied in tuberous sclerosis complex. We aimed to correlate the quantity of reconstructed white matter tracts with the degree of neurologic impairment of subjects with the use of DTI and determined differences in white matter integrity between patients with tuberous sclerosis complex and controls with the use of voxelwise analysis. In this case-control study, 16 patients with tuberous sclerosis complex and 12 control subjects underwent DTI. Major white matter tracts, comprising bilateral PF and CF, were reconstructed and assessed for quantity, represented by NOP and NOF. A neurologic severity score, based on the presence of developmental disability, seizure, autism, and other neuropsychiatric disorders, was calculated for each subject. We then correlated this score with white matter quantity. Voxelwise tract-based spatial statistics was used to determine differences in FA, axial, and radial diffusivity values between the tuberous sclerosis complex group and the control subjects. NOP and NOF of CF, bilateral PF, and MWT in the tuberous sclerosis complex group were all significantly lower than those in the control subjects (P < .05). The neurologic severity score was moderately negatively correlated with NOF and NOP regarding CF (r = -.70; r = -.75), bilateral PF (r = -.66; r = -.68), and MWT (r = -.71; r = -.74). Tract-based spatial statistics revealed that patients with tuberous sclerosis complex showed a widespread reduction (P < .05) in FA and axial diffusivity in most cerebral white matter regions. Patients with tuberous sclerosis complex with reduced residual white matter were neurologically more severely affected. Tract-based spatial statistics revealed decreased FA and axial diffusivity of the cerebral white matter in the tuberous sclerosis complex group, suggesting reduced axonal integrity.

White Matter Microstructural Integrity in Youth With Type 1 Diabetes

Decreased white and gray matter volumes have been reported in youth with type 1 diabetes mellitus (T1DM), but the effects of hyperglycemia on white matter integrity have not been quantitatively assessed during brain development. We performed diffusion tensor imaging, using two complimentary approaches—region-of-interest and voxelwise tract-based spatial statistics—to quantify white matter integrity in a large retrospective study of T1DM youth and control participants. Exposure to chronic hyperglycemia, severe hyperglycemic episodes, and severe hypoglycemia, as defined in the Diabetes Control and Complications Trial (DCCT), were estimated through medical records review, HbA1c levels, and interview of parents and youth. We found lower fractional anisotropy in the superior parietal lobule and reduced mean diffusivity in the thalamus in the T1DM group. A history of three or more severe hyperglycemic episodes was associated with reduced anisotropy and increased diffusivity in the superior parietal lobule and increased diffusivity in the hippocampus. These results add microstructural integrity of white matter to the range of structural brain alterations seen in T1DM youth and suggest vulnerability of the superior parietal lobule, hippocampus, and thalamus to glycemic extremes during brain development. Longitudinal analyses will be necessary to determine how these alterations change with age or additional glycemic exposure.