High angular resolution diffusion imaging reveals intravoxel white matter fiber heterogeneity.

Magnetic resonance (MR) diffusion tensor imaging (DTI) can resolve the white matter fiber orientation within a voxel provided that the fibers are strongly aligned. However, a given voxel may contain a distribution of fiber orientations due to, for example, intravoxel fiber crossing. The present study sought to test whether a geodesic, high b-value diffusion gradient sampling scheme could resolve multiple fiber orientations within a single voxel. In regions of fiber crossing the diffusion signal exhibited multiple local maxima/minima as a function of diffusion gradient orientation, indicating the presence of multiple intravoxel fiber orientations. The multimodality of the observed diffusion signal precluded the standard tensor reconstruction, so instead the diffusion signal was modeled as arising from a discrete mixture of Gaussian diffusion processes in slow exchange, and the underlying mixture of tensors was solved for using a gradient descent scheme. The multitensor reconstruction resolved multiple intravoxel fiber populations corresponding to known fiber anatomy. Ma     

Multiscale white matter fiber tract coregistration: a new feature-based approach to align diffusion tensor data.

In this paper an automatic multiscale feature-based rigid-body coregistration technique for diffusion tensor imaging (DTI) based on the local curvature kappa and torsion tau of the white matter (WM) fiber pathways is presented. As a similarity measure, the mean squared difference (MSD) of corresponding fiber pathways in (kappa, tau)-space is chosen. After the MSD is minimized along the arc length of the curve, principal component analysis is applied to calculate the transformation parameters. In addition, a scale-space representation of the space curves is incorporated, resulting in a multiscale robust coregistration technique. This fully automatic technique inherently allows one to apply region of interest (ROI) coregistration, and is adequate for performing both global and local transformations. Simulations were performed on synthetic DT data to evaluate the coregistration accuracy and precision. An in vivo coregistration example is presented and compared with a voxel-based coregistration approach, demonstrating the feasibility and advantages of the proposed technique to align DT data of the human brain.     

Improved white matter fiber tracking using stochastic labeling.

Diffusion tensor imaging (DTI) promises a robust means of visualizing in vivo white matter fibers in individual subjects, and of inferring direct connectivity between distant points in the brain. By following the primary eigenvector of the diffusion tensor, trajectories may be defined that trace the path of the underlying fiber tract. However, fiber tracking is prone to cumulative error from acquisition noise and partial volume, which limits the repeatability of such techniques. An image-processing method based on stochastic labeling, by which the noisy primary eigenvectors may be reconfigured according to anatomically reasonable assumptions, is described. The method's potential to improve fiber tracking is first demonstrated on numerical test data. It is then applied to real data acquired from healthy volunteers. Trajectories defined within the corpus callosum and the pyramidal tracts are rendered using 3D graphic imaging software, and the results are compared before and after processing. Fiber tracking was shown to produce anatomically plausible results, and typical errors were largely resolved by the method. Further, the sensitivity of trajectories to their start point was greatly reduced after processing. The use of stochastic labeling may therefore improve the reliability of experiments using white matter fiber tracking.     

Tractography-based quantitation of diffusion tensor imaging parameters in white matter tracts of preterm newborns

PURPOSE: To evaluate the feasibility of performing diffusion tensor tractography (DTT) to map and quantify the pyramidal white matter tracts of premature newborns. MATERIALS AND METHODS: Fourteen diffusion tensor MRI (DTI) examinations of nine premature newborns were evaluated. DTT was performed to segment bilateral pyramidal tracts, using a fiber-tracking algorithm originating in the cerebral peduncle (CP) and filtering through the posterior limb of the internal capsule (PLIC) and precentral gyrus (PCG). Voxels containing the resulting tracts were then used for quantitation of DTI parameters along the tract. The DTT-based tract measurements were compared with standard manually placed region-of-interest (ROI) measurements at four locations along the pyramidal tract, and the reproducibility of each technique was evaluated. RESULTS: DTT demonstrated improved reproducibility over manual ROI measurement for pyramidal tract quantitation and was less subject to intra-operator variability (P < 0.0001, Fisher test for equal variance). In general, the anatomic locations and measurements obtained with the two techniques were in good agreement, although some systematic differences were identified in the PLIC and CP. CONCLUSION: Fiber DTT is feasible in premature newborns, provides more reproducible tract measurements than manual ROI methods, and allows quantitation along the entire tract for more detailed DTI assessment of white matter maturation.     

Study of the effect of CSF suppression on white matter diffusion anisotropy mapping of healthy human brain.

Healthy human brain diffusion anisotropy maps derived from standard spin echo diffusion tensor imaging (DTI) were compared with those using fluid-attenuated inversion recovery (FLAIR) preparation prior to DTI to null the signal from cerebrospinal fluid (CSF). Consistent comparisons entailed development of DTI postprocessing methods, image masking based on fitting quality, and an objective region-of-interest-based method for assessment of white matter extent. FLAIR DTI achieved an extended delineation of major white-matter tracts (genu, splenium, and body of the corpus callosum) close to large CSF-filled spaces (lateral ventricles), but did not affect representation of tracts remote from CSF (internal and external capsules and coronal radiation). This result, which was detectable qualitatively (visual inspection), was verified quantitatively by analyses of the relative anisotropy (RA) distribution over white matter structures for 11 subjects. FLAIR DTI thus suppresses the CSF signal that otherwise masks underlying anisotropic parenchymal tissue through partial volume averaging.     

Assessing atrophy of the major white matter fiber bundles of the brain from diffusion tensor MRI data.

Brain atrophy is a typical feature of many neurological conditions. Therefore, quantitative evaluation and spatial characterization of atrophy are potentially useful for monitoring the evolution of central nervous system (CNS) disorders. In this study, a method for measuring atrophy of the major white matter (WM) fiber bundles in the brain using diffusion tensor (DT) MRI data is developed. To this end, an atlas was created from sets of diffusion anisotropy images from normal subjects, and the deformations necessary to match single subject anisotropy images to this atlas were then computed. Because diffusion anisotropy images were used, this approach should be sensitive to fiber bundle volume changes in the same way that using T1-weighted images allows gray matter volume changes to be measured. The Jacobian determinant of the deformation field for each subject was then used as a measure of contraction or expansion of the tissue at each image voxel. An overview of the nonlinear registration problem is given; then an optimization of the parameters for the chosen algorithm is performed and the method for producing the atlas is described. The effectiveness of the method was then tested on data from five patients with multiple sclerosis (MS) and two patients with amyotrophic lateral sclerosis (ALS).     

Characterization of white matter alterations in phenylketonuria by magnetic resonance relaxometry and diffusion tensor imaging.

A multimodal MR study including relaxometry, diffusion tensor imaging (DTI), and MR spectroscopy was performed on patients with classical phenylketonuria (PKU) and matched controls, to improve our understanding of white matter (WM) lesions. Relaxometry yields information on myelin loss or malformation and may substantiate results from DTI attributed to myelin changes. Relaxometry was used to determine four brain compartments in normal-appearing brain tissue (NABT) and in lesions: water in myelin bilayers (myelin water, MW), water in gray matter (GM), water in WM, and water with long relaxation times (cerebrospinal fluid [CSF]-like signals). DTI yielded apparent diffusion coefficients (ADCs) and fractional anisotropies. MW and WM content were reduced in NABT and in lesions of PKU patients, while CSF-like signals were significantly increased. ADC values were reduced in PKU lesions, but also in the corpus callosum. Diffusion anisotropy was reduced in lesions because of a stronger decrease in the longitudinal than in the transverse diffusion. WM content and CSF-like components in lesions correlated with anisotropy and ADC. ADC values in lesions and in the corpus callosum correlated negatively with blood and brain phenylalanine (Phe) concentrations. Intramyelinic edema combined with vacuolization is a likely cause of the WM alterations. Correlations between diffusivity and Phe concentrations confirm vulnerability of WM to high Phe concentrations.     

Water diffusion anisotropy in white and gray matter of the human spinal cord

PURPOSE: To develop a reliable technique for diffusion imaging of the human spinal cord at 1.5 Tesla and to assess potential differences in diffusion anisotropy in cross-sectional images. MATERIALS AND METHODS: A single-shot echo-planar imaging sequence with double spin-echo diffusion preparation was optimized regarding cerebrospinal fluid artifacts, effective resolution, and contrast-to-noise ratios. Eleven healthy volunteers participated in the study for quantitative characterization of diffusion anisotropy in white matter (WM) and gray matter (GM) by means of two diffusion encoding schemes: octahedral-six-directions for fractional anisotropy (FA) evaluation and orthogonal-three-directions for anisotropy index (AI) calculation. RESULTS: Pulse-trigger gated sequences with optimal matrix size (read x phase = 64 x 32) and b-value (700 s/mm(2)) allowed the acquisition of high-resolved images (voxel size = 0.9 x 0.9 x 5.0 mm(3)). The GM butterfly shape was recognizable in both AI and FA maps. Both encoding schemes yielded high diffusion anisotropy in dorsal WM (FA = 0.79 +/- 0.07; AI = 0.39 +/- 0.04). Lateral WM showed slightly lower anisotropy (FA = 0.69 +/- 0.08; AI = 0.35 +/- 0.03) than dorsal WM. Clearly smaller anisotropy was found in regions containing GM (FA = 0.45 +/- 0.06; AI = 0.21 +/- 0.05). CONCLUSION: Diffusion anisotropy data of the spinal cord can be obtained in a clinical setting. Its application seems promising for the assessment of neurological disorders.     

Effects of echo time on diffusion quantification of brain white matter at 1.5T and 3.0T

The aim was to investigate the effects of echo time (TE) on diffusion quantification of brain white matter. Seven rhesus monkeys (all males; age, 4–6 years; weight, 5–7 kg) underwent diffusion tensor imaging (DTI) with a series of TEs in 1.5T and 3.0T MR scanners. The mean diffusivity (MD), fractional anisotropy (FA), primary (λ₁), and transverse eigenvalues (λ₂₃) were measured in a region of interest at the bilateral internal capsule. Pearson correlation showed that the FA and λ₁ increased and λ₂₃ decreased with TE both at 1.5T and 3.0T except for the MD. Repeated measurement analysis of variance (ANOVA) also showed significantly higher FA and lower MD and λ₂₃ at 3.0T than those at 1.5T (P < 0.01), but no statistical differences were found in λ₁ between these two field strengths (P = 0.709). These findings implied that TE and field strength might influence diffusion quantification in brain white matter. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

The effect of Tai Chi practice on brain white matter structure: a diffusion tensor magnetic resonance imaging study

Diffusion tensor imaging (DTI) measures the displacement of water molecules across tissue components and thus provides information on the microstructure of brain white matter. This study examined the effect of Tai Chi and the relation of Tai Chi experiences and skills with brain white matter. Fractional anisotropy (FA) was obtained from the DTI magnetic resonance images of two group participants, namely, the long-term Tai Chi practitioners and sedentary counterparts. Whole-brain voxel-based analysis showed that the Tai Chi group had higher FA in the splenium of corpus callosum (p = 0.015) than the control group. Rank correlation analysis revealed that in the Tai Chi group, the FA value of the splenium of corpus callosum was moderately related with exercise duration (r = 0.45, p = 0.045) but highly related with skill level (r = 0.699, p = 0.001). Long-term Tai Chi practice could benefit to the brain white matter, and these impacts were correlated with exercise duration and skill level.     

Directional correlation in white matter tracks of the human brain

PURPOSE: To describe a technique for the detection of distinct brain fibers in sets of magnetic resonance (MR) diffusion tensor imaging (DTI) data. MATERIALS AND METHODS: MR-DTI can be used for a tractography of brain fibers presuming a data set of high spatial resolution and high signal to noise. A less demanding technique for the visualization of discrete brain fiber bundles involves segmentation. By using a region-growing algorithm, those voxels that have a direction similar to that of the major eigenvector in neighboring voxels of a data set can be marked. It has been shown recently by Mori et al (1) that this technique can be successfully applied to data from a single slice of a mouse brain. In this study, the segmentation technique was applied with modifications to multislice DTI data from the human brain. RESULTS: A distinct segmentation of various brain fiber bundles could be achieved by the use of a two-step algorithm. In the first step, voxels within large fiber tracts-such as corticofugal tracts (e.g., corticospinal tract) and the optic radiation-were segmented by starting the region-growing algorithm in the corpus callosum (CC) and erasing this major structure from the data set. In the second step, remaining voxels were segmented by the same algorithm; this revealed a good assignment of the similarly oriented fibers derived by segmentation to the anatomically given brain lobes. This two-step procedure was successfully applied to DTI data of six healthy volunteers. CONCLUSION: The segmentation technique for DTI data proposed by Mori et al (1) for data from mouse brains can be applied to multislice data from the human brain by using a two-step algorithm including a masking of the major fiber tracts.     

Toward accurate diagnosis of white matter pathology using diffusion tensor imaging.

Diffusion tensor imaging (DTI) has been widely applied to investigate injuries in the central nervous system (CNS) white matter (WM). However, the underlying pathological correlates of diffusion changes have not been adequately determined. In this study the coregistration of histological sections to MR images and a pixel-based receiver operating characteristic (ROC) analysis were used to compare the axial (lambda( parallel)) and radial (lambda( perpendicular)) diffusivities derived from DTI and histological markers of axon (phosphorylated neurofilament, SMI-31) and myelin (Luxol fast blue (LFB)) integrity, respectively, in two different patterns of injury to mouse spinal cord (SC) WM. In contusion SC injury (SCI), a decrease in lambda( parallel) matched the pattern of axonal damage with high accuracy, but lambda( perpendicular) did not match the pattern of demyelination detected by LFB. In a mouse model of multiple sclerosis (MS), lambda( perpendicular) and lambda( parallel) did not match the patterns of demyelination or axonal damage, respectively. However, a region of interest (ROI) analysis suggested that lambda( perpendicular)-detected demyelination paralleled that observed with LFB, and lambda( parallel) decreased in both regions of axonal damage and normal-appearing WM (NAWM) as visualized by SMI-31. The results suggest that directional diffusivities may reveal abnormalities that are not obvious with SMI-31 and LFB staining, depending on the type of injury.     

Visualization and analysis of white matter structural asymmetry in diffusion tensor MRI data.

This work presents a method that permits the characterization, quantification, and 3D visualization of white matter structural information contained within diffusion tensor MR imaging (DT-MRI) data. In this method, regions within the brain are defined as possessing linear, planar, or spherical diffusion. Visualization of this diffusion metric data is realized by generating streamtube and streamsurface models to represent regions of linear and planar diffusion. Quantification of differences in diffusion anisotropy between different regions of interest (ROIs) is then achieved by analyzing 2D barycentric histograms created from the complete distribution of diffusion metric values measured in each region. In four healthy volunteers, there was only a small degree of asymmetry (epsilon) in the number of linear, planar, or spherical diffusion voxels between the right and left hemispheres (epsilon approximately equal to +/- 2%). However, in a patient with a metastatic brain lesion there was marked asymmetry in both linear (epsilon approximately -10%) and planar (epsilon approximately equal to 5%) diffusion between comparable ipsilateral and contralateral regions, with a significant reduction in the number of linear diffusion voxels and an increase in the number of planar diffusion voxels in the tumor-bearing hemisphere. These results demonstrate the potential of this approach to characterize brain structure in both healthy and diseased subjects.     

White matter microstructural abnormalities in children with spina bifida myelomeningocele and hydrocephalus: a diffusion tensor tractography study of the association pathways

PURPOSE: To quantify microstructural abnormalities in the major association pathways of children affected by spina bifida myelomeningocele (SBM) and shunted hydrocephalus using whole-brain diffusion tensor imaging (DTI). MATERIALS AND METHODS: The institutional review board approved this Health Insurance Portability and Accountability Act (HIPAA)-compliant study and written informed consent/assent were obtained prior to the study. The 69 participants included 38 children with SBM and shunted hydrocephalus (age mean +/- SD = 12.30 +/- 2.10 years; 22 boys; 10 left-handed) and 31 age- and sex-matched normally-developing children (11.56 +/- 2.72 years; 15 boys, four left-handed). Diffusion tensor tractography (DTT) was performed to delineate and quantify bilaterally four major association pathways (arcuate, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculi). RESULTS: The group with SBM did not exhibit the pattern of age-related decreases in the diffusivities observed in the controls. The transverse and axial diffusivities were significantly elevated in most of the white matter pathways of the participants with SBM. The fractional anisotropy (FA) was significantly lower in most of the association pathways. Many of the association pathways were not traceable in some participants with SBM compared to the controls at the selected FA thresholds. CONCLUSION: DTT revealed diffusion tensor characteristics of abnormal development (nonvisualization/poor visualization of tracts, downward arrow FA, upward arrow diffusivities), impairment in myelination (upward arrow transverse diffusivity) as well as abnormalities in intrinsic axonal characteristics and extraaxonal/extracellular space (upward arrow axial diffusivity) in the association pathways of the SBM children. The differences in the diffusion metrics observed in the children with SBM are suggestive of abnormal white matter development and persistent degeneration with increased age.     

Altered white matter diffusion anisotropy in normal and preterm infants at term‐equivalent age

To investigate white matter (WM) development, voxelwise analyses of diffusion tensor MRI (DTMRI) data, acquired from 12 very preterm and 11 preterm infants with gestational ages (GA) ranging from 25 to 29 and 29 to 32 weeks, respectively, and 10 newborn normal term infants were performed. T₂ relaxation measures were also generated to assess brain water content. Compared with newborn term infants, very preterm infants were found to possess reduced fractional anisotropy (FA) within the frontal lobe, and a number of anterior and posterior commissural pathways. Preterm infants possessed reduced FA mainly within the posterior regions of the corpus callosum. Unexpectedly, we observed significantly reduced FA and increased T₂ within a number of corticospinal projections in the newborn term infants compared to the preterm groups. This finding may reflect increased water concentration and/or a lowering of FA due to the presence of crossing interhemispheric WM projections. These findings indicate that care should be taken when interpreting FA indices without knowledge of the possible effects of water concentration in the newborn infant brain. Magn Reson Med 60:761–767, 2008. © 2008 Wiley‐Liss, Inc.     

In vivo mapping of the fast and slow diffusion tensors in human brain.

Recent studies have shown that the diffusional signal decay in human brain is non-monoexponential and may be described in terms of compartmentalized water fractions. Diffusion tensor imaging (DTI), which provides information about tissue structure and orientation, typically uses b values up to 1000 s x mm(-2) so that the signal is dominated by the fast diffusing fraction. In this study b factors up to 3500 s x mm(-2) are utilized, allowing the diffusion tensor properties of the more slowly diffusing fraction to be mapped for the first time. The mean diffusivity (MD) of the slow diffusion tensor was found to exhibit strong white/gray matter (WM/GM) contrast. Maps depicting the principal direction of the slow tensor indicated alignment with the fast tensor and the known orientation of the WM pathways.     

Dynamic corticospinal white matter connectivity changes during stroke recovery: A diffusion tensor probabilistic tractography study

Purpose

To investigate corticospinal tract connectivity changes at the cortical surface using diffusion tensor imaging (DTI) tractography during recovery from stroke.

Materials and Methods

Using data from 10 stroke patients (four subcortical) and six elderly controls, we developed an automated method to quantify altered motor connectivity that involves the use of a simplified cortical surface model as a seed mask with target regions defined within the corticospinal tracts to initiate a probabilistic tractography algorithm.

Results

We found no change in volume overlap of the generated corticospinal tracts in the stroke patients compared to controls, but significant connectivity changes at the boundary of the simplified cortical surface mask, especially within the ipsilesional hemisphere of stroke patients over time. Using the cortical regions with significantly enhanced connectivity as a seed mask on the patient data, tracts that are directly associated with stroke recovery can be delineated. Measures of uncertainty in fiber orientation within these fiber tracts significantly correlated with functional outcome.

Conclusion

The novel findings from this study highlight the usefulness of this methodology to study white matter repair/reorganization during stroke recovery. J. Magn. Reson. Imaging 2009;29:529–536. © 2009 Wiley‐Liss, Inc.     

Biexponential diffusion tensor analysis of human brain diffusion data.

Several studies have shown that in tissues over an extended range of b-factors, the signal decay deviates significantly from the basic monoexponential model. The true nature of this departure has to date not been identified. For the current study, line scan diffusion images of brain suitable for biexponential diffusion tensor analysis were acquired in normal subjects on a clinical MR system. For each of six noncollinear directions, 32 images with b-factors ranging from 5 to 5000 s/mm2 were collected. Biexponential fits yielded parameter maps for a fast and a slow diffusion component. A subset of the diffusion data, consisting of the images obtained at the conventional range of b-factors between 5 and 972 s/mm2, was used for monoexponential diffusion tensor analysis. Fractional anisotropy (FA) of the fast-diffusion component and the monoexponential fit exhibited no significant difference. FA of the slow-diffusion biexponential component was significantly higher, particularly in areas of lower fiber density. The principal diffusion directions for the two biexponential components and the monoexponential solution were largely the same and in agreement with known fiber tracts. The second and third diffusion eigenvector directions also appeared to be aligned, but they exhibited significant deviations in localized areas.