Dataset Information

Differential development of human brain white matter tracts.

ABSTRACT: Neuroscience is increasingly focusing on developmental factors related to human structural and functional connectivity. Unfortunately, to date, diffusion-based imaging approaches have only contributed modestly to these broad objectives, despite the promise of diffusion-based tractography. Here, we report a novel data-driven approach to detect similarities and differences among white matter tracts with respect to their developmental trajectories, using 64-direction diffusion tensor imaging. Specifically, using a cross-sectional sample comprising 144 healthy individuals (7 to 48 years old), we applied k-means cluster analysis to separate white matter voxels based on their age-related trajectories of fractional anisotropy. Optimal solutions included 5-, 9- and 14-clusters. Our results recapitulate well-established tracts (e.g., internal and external capsule, optic radiations, corpus callosum, cingulum bundle, cerebral peduncles) and subdivisions within tracts (e.g., corpus callosum, internal capsule). For all but one tract identified, age-related trajectories were curvilinear (i.e., inverted 'U-shape'), with age-related increases during childhood and adolescence followed by decreases in middle adulthood. Identification of peaks in the trajectories suggests that age-related losses in fractional anisotropy occur as early as 23 years of age, with mean onset at 30 years of age. Our findings demonstrate that data-driven analytic techniques may be fruitfully applied to extant diffusion tensor imaging datasets in normative and neuropsychiatric samples.

SUBMITTER: Imperati D

PROVIDER: S-EPMC3166135 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Differential development of human brain white matter tracts.

Imperati Davide D Colcombe Stan S Kelly Clare C Di Martino Adriana A Zhou Juan J Castellanos F Xavier FX Milham Michael P MP

PloS one 20110831 8

Neuroscience is increasingly focusing on developmental factors related to human structural and functional connectivity. Unfortunately, to date, diffusion-based imaging approaches have only contributed modestly to these broad objectives, despite the promise of diffusion-based tractography. Here, we report a novel data-driven approach to detect similarities and differences among white matter tracts with respect to their developmental trajectories, using 64-direction diffusion tensor imaging. Speci ...[more]

PMID: 21909351

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Project description:Damage to the structural connections of the thalamus is a frequent feature of traumatic brain injury (TBI) and can be a key factor in determining clinical outcome. Until recently it has been difficult to quantify the extent of this damage in vivo. Diffusion tensor imaging (DTI) provides a validated method to investigate traumatic axonal injury, and can be applied to quantify damage to thalamic connections. DTI can also be used to assess white matter tract structure using tractography, and this technique has been used to study thalamo-cortical connections in the healthy brain. However, the presence of white matter injury can cause failure of tractography algorithms. Here, we report a method for investigating thalamo-cortical connectivity that bypasses the need for individual tractography. We first created a template for a number of thalamo-cortical connections using probabilistic tractography performed in ten healthy subjects. This template for investigating white matter structure was validated by comparison with individual tractography in the same group, as well as in an independent control group (N=11). We also evaluated two methods of masking tract location using the tract skeleton generated by tract based spatial statistics, and a cerebrospinal fluid mask. Voxel-wise estimates of fractional anisotropy derived from the template were more strongly correlated with individual tractography when both types of masking were used. The tract templates were then used to sample DTI measures from a group of TBI patients (N=22), with direct comparison performed against probabilistic tractography in individual patients. Probabilistic tractography often failed to produce anatomically plausible tracts in TBI patients. Importantly, we show that this problem increases as tracts become more damaged, and leads to underestimation of the amount of traumatic axonal injury. In contrast, the tract template can be used in these cases, allowing a more accurate assessment of white matter damage. In summary, we propose a method suitable for assessing specific thalamo-cortical white matter connections after TBI that is robust to the presence of varying amounts of traumatic axonal injury, as well as highlighting the potential problems of applying tractography algorithms in patient populations.

Project description:White matter hyperintensities of presumed vascular origin are frequently observed on magnetic resonance imaging in normal aging. They are typically found in cerebral small vessel disease and suspected culprits in the etiology of complex age- and small vessel disease-related conditions, such as late-onset depression. White matter hyperintensities may interfere with surrounding white matter metabolic demands by disrupting fiber tract integrity. Meanwhile, risk factors for small vessel disease are thought to reduce tissue oxygenation, not only by reducing regional blood supply, but also by impairing capillary function. To address white matter oxygen supply-demand balance, we estimated voxel-wise capillary density as an index of resting white matter metabolism, and combined estimates of blood supply and capillary function to calculate white matter oxygen availability. We conducted a cross-sectional study with structural, perfusion- and diffusion-weighted magnetic resonance imaging in 21 patients with late-onset depression and 21 controls. We outlined white matter hyperintensities and used tractography to identify the tracts they intersect. Perfusion data comprised cerebral blood flow, blood volume, mean transit time and relative transit time heterogeneity-the latter a marker of capillary dysfunction. Based on these, white matter oxygenation was calculated as the steady state cerebral metabolic rate of oxygen under the assumption of normal tissue oxygen tension and vice versa. The number, volume and perfusion characteristics of white matter hyperintensities did not differ significantly between groups. Hemodynamic data showed white matter hyperintensities to have lower blood flow and blood volume, but higher relative transit time heterogeneity, than normal-appearing white matter, resulting in either reduced capillary metabolic rate of oxygen or oxygen tension. Intersected tracts showed significantly lower blood flow, blood volume and capillary metabolic rate of oxygen than normal-appearing white matter. Across groups, lower lesion oxygen tension was associated with higher lesion number and volume. Compared with normal-appearing white matter, tissue oxygenation is significantly reduced in white matter hyperintensities as well as the fiber tracts they intersect, independent of parallel late-onset depression. In white matter hyperintensities, reduced microvascular blood volume and concomitant capillary dysfunction indicate a severe oxygen supply-demand imbalance with hypoxic tissue injury. In intersected fiber tracts, parallel reductions in oxygenation and microvascular blood volume are consistent with adaptations to reduced metabolic demands. We speculate, that aging and vascular risk factors impair white matter hyperintensity perfusion and capillary function to create hypoxic tissue injury, which in turn affect the function and metabolic demands of the white matter tracts they disrupt.

Dataset Information

Differential development of human brain white matter tracts.

Publications

Differential development of human brain white matter tracts.

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