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.

We present and validate a novel diffusion tensor imaging (DTI) approach for segmenting the human whole-brain into partitions representing grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF). The approach utilizes the contrast among tissue types in the DTI anisotropy vs. diffusivity rotational invariant space. The DTI-based whole-brain GM and WM fractions (GMf and WMf) are contrasted with the fractions obtained from conventional magnetic resonance imaging (cMRI) tissue segmentation (or clustering) methods that utilized dual echo (proton density-weighted (PDw), and spin-spin relaxation-weighted (T2w) contrast, in addition to spin-lattice relaxation weighted (T1w) contrasts acquired in the same imaging session and covering the same volume. In addition to good correspondence with cMRI estimates of brain volume, the DTI-based accurately depicts expected age vs. WM and GM volume-to-total intracranial brain volume percentage trends on the rapidly developing brains of a cohort of 29 children (6-18 years). This approach promises to extend DTI utility to both micro and macrostructural aspects of tissue organization.

In this study of a cohort of 33 young and middle-age adults (19 -59 years) we report simultaneous measurements of normal age-related changes in the caudate nuclei volume, diffusion tensor metrics, and T 2 relaxation time. Both the absolute caudate volume and its ratio relative to the total intracranial volume decreased rapidly with age in both men and women (r ‫؍‬ ؊0.55; P < 0.001). The fractional diffusion tensor anisotropy of the caudate nuclei increased with age in both males and females (r ‫؍‬ 0.48; P ‫؍‬ 0.005). The corresponding age correlations of the caudate axial (r ‫؍‬ 0.17; P ‫؍‬ 0.35), transverse (r ‫؍‬ ؊0.12; P ‫؍‬ 0.50), mean diffusivities (r ‫؍‬ 0.018; P ‫؍‬ 0.92), and T 2 relaxation times (r ‫؍‬ 0.194; P ‫؍‬ 0.28) were weaker and did not reach statistical significance (P > 0.05). Our preliminary findings warrant further studies on the older and aging adults and indicate that caudate diffusion tensor imaging-derived metrics can be used as surrogates in modeling the neuronal substrates of gray matter atrophy. Magn Reson Med 59:7-13, 2008.

Purpose:To investigate the utility of caudate nuclei (CN) macro-and microstructural metrics as markers of gray matter degeneration in healthy adults and relapsing-remitting multiple sclerosis (RRMS) patients. Materials and Methods:The normal age-and pathologyrelated changes in caudate nuclei volume (CNV), the corresponding diffusion tensor metrics, and the T 2 relaxation times were measured in a cohort of 32 healthy adults (12 men/20 women; age range 21-59 years) and 32 agematched RRMS patients (8 men/34 women; age range 21-57 years). Results:Smaller values in both the absolute CNV and the caudate volume ratio relative to the total intracranial volume (CNVp) were observed in the RRMS group relative to healthy controls. The fractional anisotropy (FA), based on the diffusion tensor imaging (DTI) of the CN increased with age in healthy adults (r ϭ 0.52; P ϭ 0.003) but not in patients (r ϭ 0.28; P ϭ 0.12). The caudate FA value was approximately 9% larger in RRMS patients relative to controls (P ϭ 0.001). The mean diffusivity of the CN was greater in the RRMS group compared to controls (P ϭ 0.02). The caudate T 2 relaxation times were smaller in the RRMS group relative to the control group (3% reduction, P ϭ 0.05). T 2 relaxation times did not exhibit age-related changes (P Ͼ 0.35) in either cohort. Strong and significant correlations between CNVp and whole-brain lesion load (r ϭ -0.48; P ϭ 0.005) and whole-brain CSF fraction (r ϭ -0.46; P ϭ 0.01) were also noted. Conclusion:These preliminary findings indicate that caudate DTI-derived metrics can serve as potential quantitative radiological markers of MS pathology.

Object Patients with spina bifida (SB) have variable intellectual outcomes. The authors used diffusion tensor (DT) imaging to quantify whole-brain volumes of gray matter, white matter, and cerebrospinal fluid (CSF), and perform regional quantitative microstructural assessments of gray matter nuclei and white matter tracts in relation to intellectual outcomes in patients with SB. Methods Twenty-nine children with myelomeningoceles and 20 age- and sex-matched children with normal neural tube development underwent MR imaging with DT image acquisition and assessments of intelligence. The DT imaging–derived metrics were the fractional anisotropy (FA), axial (parallel), and transverse (perpendicular) diffusivities. These metrics were also used to segment the brain into white matter, gray matter, and CSF. A region-of-interest analysis was conducted of the white and gray matter structures implicated in hydrocephalus. Results The amount of whole-brain gray matter was decreased in patients with SB, with a corresponding increase in CSF (p < 0.0001). Regional transverse diffusivity in the caudate nucleus was decreased (p < 0.0001), and the corresponding FA was increased (p < 0.0001), suggesting reduced dendritic branching and connectivity. Fractional anisotropy in the posterior limb of the internal capsule increased in the myelomeningocele group (p = 0.02), suggesting elimination of some divergent fascicles; in contrast, the FA in several white matter structures (such as the corpus callosum genu [p < 0.001] and arcuate fasciculus) was reduced, suggesting disruption of myelination. Diffusion tensor imaging–metrics involving gray matter volume and the caudate nucleus, but not other structures, predicted variations in IQ (r = 0.37–0.50; p < 0.05). Conclusions Diffusion tensor imaging–derived metrics provide noninvasive neuronal surrogate markers of the pathogenesis of SB and predict variations in general intellectual outcomes in children with this condition.