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Deficits in working memory (WM) are a common consequence of pediatric traumatic brain injury (TBI) and are believed to contribute to difficulties in a range of cognitive and academic domains. Reduced integrity of the corpus callosum (CC) after TBI may disrupt the connectivity between bilateral frontoparietal neural networks underlying WM. In the present investigation, diffusion tensor imaging (DTI) tractography of eight callosal subregions (CC1-CC8) was examined in relation to measures of verbal and visuospatial WM in 74 children sustaining TBI and 49 typically developing comparison children. Relative to the comparison group, children with TBI demonstrated poorer visuospatial WM, but comparable verbal WM. Microstructure of the CC was significantly compromised in brain-injured children, with lower fractional anisotropy (FA) and higher axial and radial diffusivity metrics in all callosal subregions. In both groups of children, lower FA and/or higher radial diffusivity in callosal subregions connecting anterior and posterior parietal cortical regions predicted poorer verbal WM, whereas higher radial diffusivity in callosal subregions connecting anterior and posterior parietal, as well as temporal, cortical regions predicted poorer visuospatial WM. DTI metrics, especially radial diffusivity, in predictive callosal subregions accounted for significant variance in WM over and above remaining callosal subregions. Reduced microstructural integrity of the CC, particularly in subregions connecting parietal and temporal cortices, may act as a neuropathological mechanism contributing to long-term WM deficits. The future clinical use of neuroanatomical biomarkers may allow for the early identification of children at highest risk for WM deficits and earlier provision of interventions for these children.

Noninvasive quantitative MRI methods, such as diffusion tensor imaging (DTI), can offer insights into the structure-function relationships in human developmental brain disorders. In this article, we quantified the macrostructural and microstructural attributes of the corpus callosum (CC) in children with dyslexia and in typically developing readers of comparable age and gender. Diffusion anisotropy, and mean, radial and axial diffusivities of cross-sectional CC subregions were computed using a validated DTI methodology. The normalized posterior CC area was enlarged in children with dyslexia relative to that in typically developing children. Moreover, the callosal microstructural attributes, such as the mean diffusivity of the posterior middle sector of the CC, correlated significantly with measures of word reading and reading comprehension. Reading group differences in fractional anisotropy, mean diffusivity and radial diffusivity were observed in the posterior CC (CC5). This study demonstrates the utility of regional DTI measurements of the CC in understanding the neurobiology of reading disorders., (Copyright © 2012 John Wiley & Sons, Ltd.)

Using diffusion tensor tractography, we quantified the microstructural changes in the association, projection, and commissural compact white matter pathways of the human brain over the lifespan in a cohort of healthy right-handed children and adults aged 6-68 years. In both males and females, the diffusion tensor radial diffusivity of the bilateral arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, corticospinal, somatosensory tracts, and the corpus callosum followed a U-curve with advancing age; fractional anisotropy in the same pathways followed an inverted U-curve. Our study provides useful baseline data for the interpretation of data collected from patients.

Recent studies demonstrated that diffusion tensor imaging (DTI) can provide information regarding white matter integrity of the corpus callosum (CC). In this study, DTI parameters were compared between cocaine dependent subjects (CDs) and non-drug using controls (NCs) in midsagittal CC. DTI images were acquired from 19 CDs and 18 age-matched NCs. The midsagittal CC was segmented into: genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium. Linear mixed models analyses showed that, relative to NCs, CDs had lower fractional anisotropy (FA), higher radial diffusivity (lambda(perpendicular)), and higher mean diffusivity (D(av)) in the isthmus; higher lambda(perpendicular) and D(av) in the rostral body; and lower FA in the splenium. After including mass of lifetime alcohol use in the mixed model analysis of covariance (ANCOVA) as a covariate, significant between group differences in lambda(perpendicular) in the rostral body and isthmus remained. These results suggest that alterations in lambda(perpendicular) in the rostral body and isthmus were mainly due to cocaine use, consistent with previous studies showing that cocaine may alter myelin integrity. Between group differences in FA in the isthmus and splenium, and D(av) in the rostral body and isthmus became non-significant after inclusion of alcohol use as a covariate. This is suggestive of alcohol influencing these values, or may be related to the decreased degrees of freedom for these effects. Consistent with clinical data of greater severity of drug use in smoked versus intranasal cocaine, subjects who smoked cocaine showed lower FA and higher lambda(perpendicular) compared to intranasal CDs.

We studied the relation between cortical oscillatory rhythms and the structural integrity of the corpus callosum in 21 children with spina bifida and hydrocephalus. Participants underwent resting state neuromagnetic recordings and diffusion tensor imaging. Areas of three segments of the corpus callosum (genu, body, splenium) were derived through diffusion tensor imaging-based morphometrics. Children with spina bifida showed reduced values of spectral power in the theta, alpha and beta bands when compared with age-matched controls, but only in the posterior and temporal regions. Reduced spectral power in posterior regions correlated with decreased area of the posterior segments of the corpus callosum. Atypical cortical oscillatory activity is associated with reduced transcallosal connectivity in children with spina bifida.

Several anatomical attributes of the human corpus callosum (CC) including the midsagittal cross-sectional area, thickness, and volume, have been used to assess CC integrity. We extended our previous lifespan quantitative diffusion tensor imaging (DTI) study of the regional CC midsagittal areas to include the CC volumes obtained from DTI fiber tracking. In addition to the entire CC tracked subvolumes we normalized volume with respect to each subject's intracranial volume (ICV) and the corresponding DTI metrics of the different specialized fiber pathways of the CC on a cohort of 99 right-handed children and adults aged 7-59 years. Results indicated that the CC absolute volume, the normalized volume fraction, and the fractional anisotropy followed inverted U-shaped curves, while the radial diffusivities followed a U-shaped curve reflecting white matter progressive and regressive myelination dynamics that continue into young adulthood. Our study provides for the first time normative baseline macro- and microstructural age trajectories of the human CC subvolumes across the lifespan that can be helpful for normative behavioral and clinical studies.

The midsagittal cross-sectional area of the human corpus callosum (CC) has been used by many researchers as a marker of development, natural aging, and neurodegenerative and acquired pathologies. The availability of non-invasive MRI methods for quantifying the macrostructural and microstructural organization of the CC would help to clarify the CC contribution to behavior and cognition in both health and disease. In this report, we extended and validated the ability of a recently described semi-automated diffusion tensor imaging tissue segmentation method to utilize the high orientation contrast of the CC on diffusion tensor imaging. Using a cohort of healthy right-handed children and adults aged 7-59 years, we show gender-independent non-linear (quadratic) and strongly correlated growth trends in the CC area and the corresponding diffusion tensor fractional anisotropy (r = 0.67; P < 1 x 10(-10)). Our results provide preliminary evidence that diffusion tensor anisotropy in the living CC may be related to the number of small myelinated fibers., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

Chronic pediatric traumatic brain injury (TBI) is associated with significant and persistent neurobehavioral deficits. Using diffusion tensor imaging (DTI), we examined area, fractional anisotropy (FA), radial diffusion, and axial diffusion from six regions of the corpus callosum (CC) in 41 children and adolescents with TBI and 31 comparison children. Midsagittal cross-sectional area of the posterior body and isthmus was similar in younger children irrespective of injury status; however, increased area was evident in the older comparison children but was obviated in older children with TBI, suggesting arrested development. Similarly, age was correlated significantly with indices of tissue microstructure only for the comparison group. TBI was associated with significant reduction in FA and increased radial diffusivity in the posterior third of the CC and in the genu. The axial diffusivity did not differ by either age or group. Logistic regression analyses revealed that FA and radial diffusivity were equally sensitive to post-traumatic changes in 4 of 6 callosal regions; radial diffusivity was more sensitive for the rostral midbody and splenium. IQ, working memory, motor, and academic skills were correlated significantly with radial diffusion and/or FA from the isthmus and splenium only in the TBI group. Reduced size and microstructural changes in posterior callosal regions after TBI suggest arrested development, decreased organization, and disrupted myelination. Increased radial diffusivity was the most sensitive DTI-based surrogate marker of the extent of neuronal damage following TBI; FA was most strongly correlated with neuropsychological outcomes.

The midsagittal corpus callosum (CC) cross-sectional area subdivisions have been used as early and sensitive markers of human brain white matter connectivity, development, natural aging and disease. Despite the simplicity and conspicuity of the appearance of the CC on anatomical magnetic resonance imaging (MRI), the published quantitative MRI literature on its regional sex and age trajectories are contradictory. The availability of noninvasive quantitative methods to assess the CC regions across the human lifespan would help clarify its contribution to behavior and cognition. In this report, we extended the utility of a recently described semi-automated diffusion tensor imaging (DTI) tissue segmentation method to utilize the high orientation contrast of the CC on DTI. Using optimized DTI methods on a cohort of 121 right-handed children and adults aged 6-68 years, we examined the CC areas and corresponding DTI metrics of the different functionally specialized sectors of the CC. Both the area and fractional anisotropy metrics followed inverted U-shaped curves, while the mean and radial diffusivities followed U-curves reflecting white matter progressive and regressive myelination dynamics that continue into young adulthood.

Purpose: To detect lesion-related focal Wallerian degeneration (WD) changes in different segments of the corpus callosum (CC) in patients with large middle cerebral arterial (MCA) territory stroke using diffusion tensor imaging (DTI)., Materials and Methods: Eight patients underwent DTI scans at three different time points: six to eight weeks, 10-12 weeks, and beyond six months of stroke onset. Eight healthy age-matched controls were also scanned using the same protocol at three different time points. Region-of-interest (ROI) analysis was performed on seven segments of the CC to determine the fractional anisotropy (FA), mean diffusivity (MD), and corresponding callosal cross-sectional areas., Results: On repeated-measures analysis of variance (ANOVA), a significant reduction in the FA values was observed from the first to the third study compared to controls, reflecting temporal degeneration in the rostrum, genu, rostral body, anterior midbody, and splenium of the CC. However, a significant temporal elevation in MD values was observed in only the rostral body and anterior midbody of the CC. This was associated with a significant region-specific reduction in the cross-sectional areas at time points beyond six months, and appears to be consistent with the loss of callosal structural components due to interruption of the cortico-callosal fibers secondary to WD., Conclusion: These results indicate that cortico-callosal topographical changes exhibit a significant temporal decline in observed FA values that is suggestive of cortico-callosal WD in patients with large MCA territory stroke.

Purpose: To investigate the utility of whole-brain diffusion tensor imaging (DTI) in elucidating the pathogenesis of multiple sclerosis (MS) using the normal-appearing white matter (NAWM) of the corpus callosum (CC) as a marker of occult disease activity., Materials and Methods: A high signal-to-noise ratio (SNR) and optimized entire brain DTI data were acquired in 26 clinically-definite relapsing and remitting multiple sclerosis (RRMS) patients and 32 age-matched healthy adult controls. The fractional anisotropy (FA) values of seven functionally distinct regions in the normal-appearing CC were compared between patients and controls., Results: This study indicates that 1) there was a gender-independent FA heterogeneity of the functionally specialized CC segments in normal volunteers; 2) FA in the MS group was significantly decreased in the anterior (P=0.0039) and posterior (P=0.0018) midbody subdivisions of the CC, possibly due to a reduction of small-caliber axons; and 3) the FA of the genu of the CC was relatively intact in the MS patients compared to the healthy age-matched controls (P=0.644), while the splenium showed an insignificant trend of reduced FA values (P=0.248). The decrease in FA in any of the CC subdivisions did not correlate with disease duration (DD) or the expanded disability status scale (EDSS) score., Conclusion: The preliminary results are consistent with published histopathology and clinical studies on MS, but not with some published DTI reports. This study provides insights into the pathogenesis of MS, and the role played by compromised axonal integrity in this disease., (Copyright (c) 2005 Wiley-Liss, Inc.)

Brain imaging studies find evidence of prefrontal cortical dysfunction in cocaine-dependent subjects. Similarly, cocaine-dependent subjects have problems with behaviors related to executive function and impulsivity. Since prefrontal cortical axonal tracts cross between hemispheres in the corpus callosum, it is possible that white matter integrity in the corpus callosum could also be diminished in cocaine-dependent subjects. The purpose of this study was to compare corpus callosum white matter integrity as measured by the fractional anisotropy (FA) on diffusion tensor imaging (DTI) between 18 cocaine-dependent subjects and 18 healthy controls. The Barratt Impulsiveness Scale (BIS-11) and a continuous performance test: the Immediate and Delayed Memory Task (IMT/DMT) were also collected. Results of the DTI showed significantly reduced FA in the genu and rostral body of the anterior corpus callosum in cocaine-dependent subjects compared to controls. Cocaine-dependent subjects also had significantly higher BIS-11 scores, greater impulsive (commission) errors, and reduced ability to discriminate target from catch stimuli (discriminability) on the IMT/DMT. Within cocaine dependent subjects there was a significant negative correlation between FA in the anterior corpus callosum and behavioral laboratory measured impulsivity, and there was a positive correlation between FA and discriminability. The finding that reduced integrity of anterior corpus callosum white matter in cocaine users is related to impaired impulse control and reduced ability to discriminate between target and catch stimuli is consistent with prior theories regarding frontal cortical involvement in impaired inhibitory control in cocaine-dependent subjects.

Tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) studies have consistently shown diminished white matter (WM) integrity for individuals with cocaine use disorder (CUD). The present study used seed-based d mapping (SDM) to determine the extent to which a systematic difference in the WM integrity of cocaine users may exist (as compared with that of healthy controls). Articles from 2006 (when TBSS was first developed) to present were reviewed, with eight selected for inclusion. Meta-analysis found lower fractional anisotropy (FA) in the genu of the corpus callosum for cocaine users, with a small-to-moderate peak effect size (Hedge's g = -0.331). Sensitivity analyses mostly supported the robustness of the obtained difference. Differences detected at exploratory thresholds for significance suggested insult to WM integrity extending beyond the corpus callosum. The present results compliment a previous region-of-interest (ROI)-based meta-analysis of DTI studies in individuals with CUD. These findings have significant implications for the potential role of neuroprotective agents in the treatment of CUD and merit additional iteration as more studies accrue in the literature. [ABSTRACT FROM AUTHOR]

In this report, we applied diffusion tensor imaging (DTI) methods in 36 patients with uncomplicated mild traumatic brain injury (mTBI) and a comparison group of 37 participants with orthopedic injury. Our aim was to characterize regional and global macro- and microstructural attributes of white matter (WM), gray matter (GM), in addition to volume and diffusivity of cerebrospinal fluid (CSF) to identify and differentiate patterns of acute and short-term recovery. Given that previous DTI reports on mTBI in adults using a region-of-interest approach implicated the corona radiata (CR), corpus callosum, and hippocampus, we analyzed and quantified DTI metrics of these regions using atlas-based methods. The normalized volume percentages of global CSF, GM, and WM were not different between the mTBI and orthopedic comparison (OC) groups at either the baseline or follow-up time points or between the baseline and follow-up time points within the OC group ( p>0.17; uncorrected for multiple comparisons). The DTI metrics did not differ between groups at either occasion. However, an increase was noted on follow-up in the OC group in the global mean diffusivity of GM (uncorrected p=0.003) and WM (uncorrected p=0.02), indicating a decrease in diffusivity at the 3-month postinjury, as compared to the baseline scan. An analysis of the DTI data collected longitudinally in the CR show insignificant changes in the OC group ( p>0.08; N=37). CR radial diffusivity was found to be elevated in the between-group comparison at baseline (mTBI1 vs. OC1), but did not differ in the within-group comparison (mTBI1 vs. mTBI2; N=19), suggesting the possible resolution of edema. Our analysis of the cross-sectional and follow-up data, which is uncorrected for multiple comparisons, demonstrates dissociation between volumetric (macrostructural) and tissue integrity (microstructural) attributes and shows the potential utility of DTI to capture transient edema in the CR. [ABSTRACT FROM AUTHOR]

Abstract: Accurate and noninvasive quantification of regional cerebral blood perfusion (CBF) of the human brain tissue would advance the study of the complex interplay between human brain structure and function, in both health and disease. Despite the plethora of works on CBF in gray matter, a detailed quantitative white matter perfusion atlas has not been presented on healthy adults using the International Consortium for Brain Mapping atlases. In this study, we present a host of assurance measures such as temporal stability, spatial heterogeneity and age effects of regional and global CBF in selected deep, cortical gray matter and white matter tracts identified and quantified using diffusion tensor imaging (DTI). We utilized whole brain high-resolution DTI combined with arterial spin labeling to quantify regional CBF on 15 healthy adults aged 23.2–57.1years. We present total brain and regional CBF, corresponding volume, mean diffusivity and fractional anisotropy spatial heterogeneity, and dependence on age as additional quality assurance measures to compare with published trends using both MRI and nuclear medicine methods. Total CBF showed a steady decrease with age in gray matter (r=−0.58; P=.03), whereas total CBF of white matter did not significantly change with age (r=0.11; P=.7). This quantitative report offers a preliminary baseline of CBF, volume and DTI measurements for the design of future multicenter and clinical studies utilizing noninvasive perfusion and DT-MRI. [Copyright &y& Elsevier]

Abstract: Microstructural metrics obtained using magnetic resonance imaging (MRI) such as transverse relaxation time and radial diffusivity have been used as in vivo markers of human brain tissue integrity. Considering the sensitivity of these parameters to some common biophysical contributors and their structural and spatial heterogeneity, we hypothesized that strong inter and intra-regional associations exist between these variables providing evidence to possible interplay between transverse relaxation time and radial diffusivity. To validate our hypothesis we obtained high resolution anatomical T1-weighted data and fused it with T2-relaxometry and diffusion tensor imaging (DTI) data on a cohort of healthy adults. The anatomical data were parcellated using FreeSurfer and then coaligned and fused with the T2 and DTI maps. Our data reveal some association between transverse relaxation and radial diffusivity that may help toward the interpretation and modeling of the biophysical contributors to the measured MRI metrics. [Copyright &y& Elsevier]

Background: Chronic stimulant abuse is associated with both impairment in decision making and structural abnormalities in brain gray and white matter. Recent data suggest these structural abnormalities may be related to functional impairment in important behavioral processes. Methodology/Principal Findings: In 15 cocaine-dependent and 18 control subjects, we examined relationships between decision-making performance on the Iowa Gambling Task (IGT) and white matter integrity as measured by diffusion tensor imaging (DTI). Whole brain voxelwise analyses showed that, relative to controls, the cocaine group had lower fractional anisotropy (FA) and higher mean of the second and third eigenvalues (λ⊥) in frontal and parietal white matter regions and the corpus callosum. Cocaine subjects showed worse performance on the IGT, notably over the last 40 trials. Importantly, FA and λ⊥ values in these regions showed a significant relationship with IGT performance on the last 40 trials. Conclusions: Compromised white matter integrity in cocaine dependence may be related to functional impairments in decision making. [ABSTRACT FROM AUTHOR]

Diffusion Tensor Imaging (DTI) may provide information regarding effects of 3,4-methylenedioxymethamphetamine (MDMA) use on brain structure. Twelve MDMA users and 20 healthy controls underwent whole brain DTI data acquisition. Fractional anisotropy (FA), mean diffusivity (Dav), and longitudinal (λ1) and transverse (λT) diffusivities were compared between MDMA users and controls in 6 regions of the corpus callosum. MDMA users also completed the Barratt Impulsiveness Scale (BIS), and a subset of subjects completed the Iowa Gambling Task (IGT). Results showed significantly smaller λ1 in the rostral body of the corpus callosum in MDMA users, with no differences between groups on λT, FA, or Dav. MDMA users also had a significantly higher BIS nonplanning score and greater preference for disadvantageous choices on the IGT. There was a significant positive correlation between λ1 in the rostral body of the corpus callosum and advantageous choices on the IGT. Further research on the etiology of these findings is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Reduced fractional anisotropy (FA) in Diffusion Tensor Imaging (DTI) has been reported in cocaine dependent subjects compared to non-drug using controls. There are several pathological mechanisms that could be responsible for these findings, since FA can be reduced through damage to axonal tracts and by neuronal loss. One way of obtaining more information about pathology underlying changes in FA on DTI is diffusion tensor eigenvalues, representing diffusion along the fiber tract (λ 1) or perpendicular to the fiber tract (λ T). Thirteen cocaine dependent subjects and 18 healthy controls underwent full brain DTI. Eigenvalues λ 1 and λ T of the corpus callosum were compared between cocaine users and controls. For λ T there was a significant interaction of group×region of corpus callosum. Exploratory analysis of the subregions showed higher λ T in the genu of the anterior corpus callosum of cocaine dependent subjects compared to control subjects. For λ 1 there was no significant interaction of group×region of corpus callosum. Based on prior studies suggesting that alteration or damage to myelin increases diffusion perpendicular to the direction of fiber tracts (λ T) with minimal effect on λ 1 these findings are consistent with altered myelin in the corpus callosum in cocaine dependent subjects. [Copyright &y& Elsevier]

Abstract: Background: : Previous MRI studies of healthy children have reported age-related white matter (WM) changes in language and motor areas of the brain. The authors investigated WM development in healthy adolescent males through age-associated changes in fractional anisotropy (FA), radial (λ ⊥) and axial (λ ||) diffusivity. Methods: : Twenty-four healthy adolescent males (mean age=16.6, SD=2.5 years) were divided into two groups with an age split of 16.9 years and underwent a whole-brain voxelwise analysis. Results: : At a threshold of p <0.001 and extent threshold of 100 contiguous voxels, several clusters with increased FA and axial diffusivity and no differences in radial diffusivity were observed in older adolescents compared to the younger adolescents in the left arcuate fasciculus, bilateral posterior internal capsule/thalamic radiation, bilateral prefrontal gyrus, right superior temporal gyrus, and posterior corpus callosum. Increased FA and λ || of several clusters along the arcuate fasciculus significantly correlated with a test of language and semantic memory. Conclusions: : These results suggest ongoing maturational changes especially in the arcuate fasiculus during late adolescence. Increased FA and λ || with no changes in radial diffusivity may reflect a developmental pattern of reduced tortuousity toward more straightened fibers and/or increased axonal fiber organization during late adolescence. [Copyright &y& Elsevier]