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The human brain thalami play essential roles in integrating cognitive, sensory, and motor functions. In multiple sclerosis (MS), quantitative magnetic resonance imaging (qMRI) measurements of the thalami provide important biomarkers of disease progression, but late development and aging confound the interpretation of data collected from patients over a wide age range. Thalamic tissue volume loss due to natural aging and its interplay with lesion-driven pathology has not been investigated previously. In this work, we used standardized thalamic volumetry combined with diffusion tensor imaging, T2 relaxometry, and lesion mapping on large cohorts of controls (N = 255, age range = 6.2-69.1 years) and MS patients (N = 109, age range = 20.8-68.5 years) to demonstrate early age- and lesion-independent thalamic neurodegeneration.

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.

The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subject's intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7-68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left>Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.

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.

Whole-brain diffusion tensor tractography (DTT) at high signal-to-noise ratio and angular and spatial resolutions were utilized to study the effects of age, sex differences, and lateral asymmetries of 6 white matter pathways (arcuate fasciculus [AF], inferior longitudinal fasciculus, inferior fronto-occipital fasciculus [IFOF], uncinate fasciculus [UF], corticospinal tract [CST], and somatosensory pathway [SS]) in 31 right-handed children (6-17 years). Fractional anisotropy (FA), a measure of the orientational variance in water molecular diffusivity, and the magnitude of water diffusivity (parallel, perpendicular, and mean diffusivity) along the pathways were quantified. Three major patterns of maturation were observed: 1) significant increase in FA with age, accompanied by significant decreases in all 3 diffusivities (e.g., left IFOF); 2) significant decreases in all three diffusivities with age without significant changes in FA (e.g., left CST); and 3) no significant age-related changes in FA or diffusivity (e.g., SS). Sex differences were minimal. Many pathways showed lateral asymmetries. In the right hemisphere, the frontotemporal (FT) segment of AF was not visualized in a substantial (29%) number of participants. FA was higher in the left hemisphere in the FT segment of AF, UF, and CST, whereas it was lower in the frontoparietal segment of AF. This study provides normative data essential for the interpretation of pediatric brain DTT measurements in both health and disease.

We used a diffusion tensor imaging-based whole-brain tissue segmentation to characterize age-related changes in (a) whole-brain grey matter, white matter, and cerebrospinal fluid relative to intracranial volume and (b) the corresponding brain tissue microstructure using measures of diffusion tensor anisotropy and mean diffusivity. The sample, a healthy cohort of 119 right-handed males and females aged 7-68 years. Our results demonstrate that white matter and grey matter volumes and their corresponding diffusion tensor anisotropy and mean diffusivity follow nonlinear trajectories with advancing age. In contrast, cerebrospinal fluid volume increases linearly with age.