Sources of T1 variance in normal human white matter

The major factors contributing to T1 variance at 0.5 T in white matter were studied in healthy people. Anatomical location of the white matter sampled and differences between individuals contributed 74% of the total variance in serial measurements of the same subjects. There was also significant change over time within an individual subject that could not be attributed to machine drift. This information permitted estimates to be made concerning adequate sample size in future studies that examine for pathological white matter T1 change.     

Automatic segmentation of brain white matter and white matter lesions in normal aging: comparison of five multispectral techniques

White matter loss, ventricular enlargement and white matter lesions are common findings on brain scans of older subjects. Accurate assessment of these different features is therefore essential for normal aging research. Recently, we developed a novel unsupervised classification method, named ‘Multispectral Coloring Modulation and Variance Identification’ (MCMxxxVI), that fuses two different structural magnetic resonance imaging (MRI) sequences in red/green color space and uses Minimum Variance Quantization (MVQ) as the clustering technique to segment different tissue types. Here we investigate how this method performs compared with several commonly used supervised image classifiers in segmenting normal-appearing white matter, white matter lesions and cerebrospinal fluid in the brains of 20 older subjects with a wide range of white matter lesion load and brain atrophy. The three tissue classes were segmented from T₁-, T₂-, T₂?- and fluid attenuation inversion recovery (FLAIR)-weighted structural MRI data using MCMxxxVI and the four supervised multispectral classifiers available in the Analyze package, namely, Back-Propagated Neural Networks, Gaussian classifier, Nearest Neighbor and Parzen Windows. Bland–Altman analysis and Jaccard index values indicated that, in general, MCMxxxVI performed better than the supervised multispectral classifiers in identifying the three tissue classes, although final manual editing was still required to deliver radiologically acceptable results. These analyses show that MVQ, as implemented in MCMxxxVI, has the potential to provide quick and accurate white matter segmentations in the aging brain, although further methodological developments are still required to automate fully this technique.     

Mapping the human brain white matter tracts relative to cortical and deep gray matter using diffusion tensor imaging at high spatial resolution

The mapping of the human brain white matter fiber networks relative to deep subcortical and cortical gray matter requires high spatial resolution which is challenged by the low signal-to-noise ratio. The purpose of this short report was to introduce a whole brain high spatial resolution diffusion tensor imaging (DTI) protocol that enabled for the first time the mapping of corticopontocerebellar, frontostriatal and thalamofrontal fiber pathways in addition to other limbic, commissural, association and projection white matter pathways relative to the segmented deep gray (e.g., caudate nuclei) and the cortical lobes. Our DTI acquisition protocol and analysis strategy provide important template for brain-behavior research and for teaching brain mapping and are clinically affordable for patient comfort.     

In vivo relaxation times of gray matter and white matter in spinal cord

In vivo relaxation times and relative spin densities of gray matter (GM) and white matter (WM) of rat spinal cord were measured. Inductively coupled implanted RF coil was used to improve the signal-to-noise ratio required for making these measurements. The estimated relaxation times (in milliseconds) are: T1(GM) = 1021+/-93, T2(GM) = 64+/-3.4, T1(WM) = 1089+/-126, and T2(WM) = 79+/-6.9. The estimated relative spin densities are: rho(GM) = (60+/-2.3)% and rho(WM) = (40+/-2.1)%. The T1 values of GM and white matter are not statistically different. However, the differences in T2 values and spin densities of GM and WM are statistically significant. These in vivo measurements indicate that the observed contrast between GM and WM in spinal cord MR images mainly arises from the differences in the spin density.     

Effects of radiation therapy on the human normal brain (white matter) visualized by MR imaging

Sequential MR imaging could provide information related to the pathological changes due to the application of external cytotoxic agents such as radiotherapy on the central nervous system. This paper describes the results of our attempt to demonstrate short-term changes associated with normal brain during and immediately following radiotherapy when the whole brain is irradiated for malignant conditions. No observable changes were found in the normal brain parenchyma in any of the patients (n = 8) in T₁-, T₂-, and proton-density-weighted images in the sequential scans in the first and second weeks and immediately following radiotherapy. Also, no changes were observed in the normal brain appearance at 2 mo (n = 6), up to 6 mo (n = 1), and up to 15 mo (n = 1) after completion of radiotherapy.     

Visualizing and characterizing white matter fiber structure and architecture in the human pyramidal tract using diffusion tensor MRI.

We used diffusion tensor imaging to assess diffusion anisotropy in the pyramidal tract in ten young, and ten elderly subjects (five males and five females in each group). The purpose of this study was to define normative values for anisotropy at different anatomic levels of the brainstem as well as to assess differences due to age, gender, and laterality. In all subjects, anisotropy was highest in the cerebral peduncle, lowest in the caudal pons, and intermediate in the medulla. In the pons and medulla the regional variability was high, with significant differences in anisotropy even between contiguous slices. Multifactorial ANOVA (performed using the average value of anisotropy within each region of interest) revealed that elderly subjects had significantly lower values than young subjects in the cerebral peduncle, with no differences in the pons and medulla. No significant differences in anisotropy due to gender and side were found. The differences in anisotropy at different levels of the brainstem reflect differences in the local architecture of white matter fibers. Anisotropy is high in the cerebral peduncle because fibers have a highly ordered arrangement, while in the pons and medulla, anisotropy is lower because the local fiber architecture is less coherent due to the presence of other fibers and nuclei. The biologic meaning of the intergroup differences in anisotropy is discussed in light of the structure and architecture of the tissue under investigation. We also consider potential sources of artifacts, such as noise and motion, partial volume contamination, anatomic mismatching, and the use of inappropriate statistical tests. We conclude that the age-related decrease in anisotropy in the cerebral peduncle is not artifactual but rather reflects subtle structural changes of the aging white matter. Our study however shows that caution must be exercised in interpreting diffusion anisotropy data.     

Assessing functional connectivity in the human brain by fMRI

Functional magnetic resonance imaging (fMRI) is widely used to detect and delineate regions of the brain that change their level of activation in response to specific stimuli and tasks. Simple activation maps depict only the average level of engagement of different regions within distributed systems. FMRI potentially can reveal additional information about the degree to which components of large-scale neural systems are functionally coupled together to achieve specific tasks. In order to better understand how brain regions contribute to functionally connected circuits, it is necessary to record activation maps either as a function of different conditions, at different times or in different subjects. Data obtained under different conditions may then be analyzed by a variety of techniques to infer correlations and couplings between nodes in networks. Several multivariate statistical methods have been adapted and applied to analyze variations within such data. An approach of particular interest that is suited to studies of connectivity within single subjects makes use of acquisitions of runs of MRI images obtained while the brain is in a so-called steady state, either at rest (i.e., without any specific stimulus or task) or in a condition of continuous activation. Interregional correlations between fluctuations of MRI signal potentially reveal functional connectivity. Recent studies have established that interregional correlations between different components of circuits in each of the visual, language, motor and working memory systems can be detected in the resting state. Correlations at baseline are changed during the performance of a continuous task. In this review, various methods available for assessing connectivity are described and evaluated.     

Alterations in diffusion properties of white matter in Williams syndrome

Diffusion tensor imaging (DTI) was used to investigate the involvement of brain white matter in Williams syndrome (WS), a genetic neurodevelopmental disorder. Whole-brain DTIs were obtained from 16 young adults with WS and 16 normal controls. A voxel-based analysis was performed to compare fractional anisotropy (FA) values between the two groups. A tract-based analysis was also performed to compare FA values between the two groups along two major white matter tracts that pass through the external capsule: the uncinate and inferior fronto-occipital fasciculi. Several regions of both increased and decreased FA were found within major white matter tracts that connect functional regions that have previously been implicated in the cognitive and neurological symptoms of the syndrome. The tract-based analysis provided additional insight into the involvement of specific white matter tracts implicated in the voxel-based analysis within the external capsule. The results from this study support previously reported changes in white matter diffusion properties in WS and demonstrate the potential usefulness for tract-based analysis in future studies of the disorder.     

Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients

External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Student's t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage.     

Modeling diffusion in white matter in the brain: a composite porous medium

We model diffusion in white matter fascicles as a problem of diffusion in an array of identical thick-walled cylindrical tubes immersed in an outer medium and arranged periodically in a regular lattice. The diffusing molecules have different diffusion coefficients and concentrations (or densities) within the tubes' inner core, membrane, myelin sheath, and within the outer medium. For an impermeable myelin sheath, diffusing molecules within the inner core are completely restricted, while molecules in the outer medium are hindered due to the tortuosity of the array of impenetrable tubes.     

Sex differences in the relationship between white matter microstructure and impulsivity in adolescents

Rapid maturational brain changes occur during adolescence--a time associated with risk-taking behaviors and improvements in cognition. The present study examined the relationship between white matter (WM) microstructure, impulsive behavior and response inhibition in female and male adolescents. Twenty-one healthy adolescents underwent diffusion tensor imaging using a 3.0-T magnetic resonance imaging system. Impulse control was assessed using the Bar-On Emotional Quotient Inventory, Youth Version. Response inhibition was assessed using the Stroop Color-Word Interference Test. Fractional anisotropy (FA), a measure of WM coherence, and trace, a measure of overall diffusivity, were determined from voxels manually placed in the midline and in the left and right forward-projecting arms of the genu and the splenium of the corpus callosum. Sex-specific differences were observed for the relationship between FA and impulsive behavior in the right anterior callosum for males and in the splenium for females. Males, compared to females, displayed significantly higher FA in the left WM region. Although trace was not associated with impulse control, trace in the genu (for females) and splenium (males and females) was associated with Stroop performance. Regional differences in trace also were evident, with lower values in the splenium observed than in all other regions. Although the latter significantly improved with age, no sex differences in impulse control or in Stroop performance were detected. The present findings provide supporting evidence for sex-related differences in the development of WM microstructure during adolescence. These data further suggest a neurobiological mechanism underlying some of the emotional and cognitive changes commonly observed in males versus females during the adolescent period.     

An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain

ZNF804A, a genomewide supported susceptibility gene for schizophrenia and bipolar disorder, has been associated with task-independent functional connectivity between the left and right dorsolateral prefrontal cortices. Several lines of evidence have converged on the hypothesis that this effect may be mediated by structural connectivity. We tested this hypothesis using diffusion tensor magnetic resonance imaging in three samples: one German sample of 50 healthy individuals, one Scottish sample of 83 healthy individuals and one Scottish sample of 84 unaffected relatives of bipolar patients. Voxel-based analysis and tract-based spatial statistics did not detect any fractional anisotropy (FA) differences between minor allele carriers and individuals homozygous for the major allele at rs1344706. Similarly, region-of-interest analyses and quantitative tractography of the genu of the corpus callosum revealed no significant FA differences between the genotype groups. Examination of effect sizes and confidence intervals indicated that this negative finding is very unlikely to be due to a lack of statistical power. In summary, despite using various analysis techniques in three different samples, our results were strikingly and consistently negative. These data therefore suggest that it is unlikely that the effects of genetic variation at rs1344706 on functional connectivity are mediated by structural integrity differences in large, long-range white matter fiber connections.     

Quantitative morphologic evaluation of white matter in survivors of childhood medulloblastoma

In survivors of pediatric brain tumors, cranial radiation therapy can cause a debilitating cognitive decline associated with decreased volume in normal-appearing white matter (NAWM). We applied fractal geometry to quantify white matter (WM) integrity in the brain of medulloblastoma survivors. Fractal features of WM were evaluated by indices of fractal dimensions (FDs) of WM intensity and boundary on T1-weighted magnetic resonance images. The FD index of WM intensity was calculated by using a fractional Brownian motion model, and the FD index of WM boundary was calculated by using a box-counting method. Fractal features of WM on 116 magnetic resonance images of 58 patients with medulloblastoma were investigated at the start of therapy (Start TX) and approximately 2 years later (After TX). Patients were assigned to one of two groups based on change in NAWM volumes. Fractal features in patients with decreased NAWM volume were significantly greater After TX, whereas those in patients with increased NAWM volumes were not. Multiple linear regression analysis showed that fractal features were strongly correlated with NAWM volumes After TX in patients with decreased NAWM volume. These results demonstrated significant deficit in NAWM integrity and WM density changes in children treated for medulloblastoma. Multiple regression analysis illustrated that deficits in NAWM integrity in these children may partly explain the decrease in NAWM volume. We conclude that fractal geometry can be used to monitor the morphologic effects of neurotoxicity in brain tumor survivors.     

Myelin contributes to the parallel orientation of axonal growth on white matter in vitro

Background  

The fly visual system is a highly ordered brain structure with well-established physiological and behavioral functions. A large number of interneurons in the posterior part of the third visual neuropil, the lobula plate tangential cells (LPTCs), respond to visual motion stimuli. In these cells the mechanism of motion detection has been studied in great detail. Nevertheless, the cellular computations leading to their directionally selective responses are not yet fully understood. Earlier studies addressed the neuropharmacological basis of the motion response in lobula plate interneurons. In the present study we investigated the distribution of the respective neurotransmitter receptors in the fly visual system, namely nicotinic acetylcholine receptors (nAChRs) and GABA receptors (GABARs) demonstrated by antibody labeling.     

Bi-exponential diffusion signal decay in normal appearing white matter of multiple sclerosis

Purpose

Our aim was to characterize bi-exponential diffusion signal changes in normal appearing white matter of multiple sclerosis (MS) patients.

Methods

Diffusion parameters were measured using mono-exponential (0–1000 s/mm²) and bi-exponential (0–5000 s/mm²) approaches from 14 relapsing-remitting subtype of MS patients and 14 age- and sex-matched controls after acquiring diffusion-weighted images on a 3T MRI system. The results were analyzed using parametric or nonparametric tests and multiple linear regression models.

Results

Mono-exponential apparent diffusion coefficient (ADC) slightly increased in controls (P=.09), but decreased significantly in MS as a function of age, nonetheless an elevated ADC was observed with increasing lesion number in patients. Bi-exponential analyses showed that the increased ADC is the result of decreased relative volume fraction of slow diffusing component (f_s). However, the fast and slow diffusion components (ADC_f, ADC_s) did not change as a function of either age in controls or lesion number and age in MS patients.

Conclusions

These data demonstrated that the myelin content of the white matter affects diffusion in relapsing-remitting subtype of multiple sclerosis that is possibly a consequence of the shift between different water fractions.     

Regularization of bending and crossing white matter fibers in MRI Q-ball fields

In diffusion magnetic resonance imaging with high-angular-resolution diffusion imaging, a set of techniques has become available that allows better acquisition and representation of multidirectional diffusion profiles, e.g., in voxels with crossing, branching and kissing fibers. The poor spatial resolution and low signal-to-noise ratio of the data, particularly when acquired under clinical conditions, prevent tractography algorithms from reliably reconstructing complex white matter structures. With cone-beam regularization, an intervoxel smoothing approach has been described, which, in this article, is refined and adapted to fibers with subvoxel bending. By introducing the concept of asymmetric orientation distribution functions (aODFs), we are able to sharpen diffusion profiles of bending fibers and estimate subvoxel curvature. We also propose a deterministic fiber-tracking algorithm that exploits the enhanced resolution of aODFs. The approach is evaluated quantitatively and compared with state-of-the-art noise-suppression techniques in a study with a biological diffusion phantom. Moreover, we present results from an in vivo study in which we demonstrate the method's ability to optimize tractography of bending fiber pathways of optic radiation.     

Segmenting brain white matter, gray matter and cerebro-spinal fluid using diffusion tensor-MRI derived indices.

Based on its ability to provide quantitative information about tissue microstructure, diffusion tensor magnetic resonance imaging (DT-MRI) might be a valuable approach to improve the reliability of segmentation of the various brain tissues.In this study, a fully automated and easy-to-implement technique based on 2D histogram analysis of DT-MRI derived images was used to segment white and gray matter of the brain from 10 healthy subjects (aged = 27-56 years). The results obtained with this novel segmentation strategy were compared to those achieved by two experienced observers using an operator-dependent segmentation on the dual-echo scans.Visual inspection of the segmented tissues from a third senior observer disclosed that the automated technique worked properly on all images from all subjects and was more accurate than the human raters in defining thalamus white and gray matter portions as well as in tissue classification at the external brain edge. In addition, this segmentation technique resulted in an average gray/white matter ratio similar to that reported by post-mortem assessment. The application of the operator-dependent segmentation strategy was extremely time-consuming and the two observers achieved poorly reproducible results.Segmenting brain white and gray matter using information from DT-MRI proved to be an accurate approach with the potential for improving the understanding of the pathophysiology of many neurologic conditions.     

Cervical spondylosis: Evaluation of microstructural changes in spinal cord white matter and gray matter by diffusional kurtosis imaging

Introduction

We investigated microstructural changes in the spinal cord, separately for white matter and gray matter, in patients with cervical spondylosis by using diffusional kurtosis imaging (DKI).

Methods

We studied 13 consecutive patients with cervical myelopathy (15 affected sides and 11 unaffected sides). After conventional magnetic resonance (MR) imaging, DKI data were acquired by using a 3 T MR imaging scanner. Values for fractional anisotropy (FA), apparent diffusion coefficient (ADC), and mean diffusional kurtosis (MK) were calculated and compared between unaffected and affected spinal cords, separately for white matter and gray matter.

Results

Tract-specific analysis of white matter in the lateral funiculus showed no statistical differences between the affected and unaffected sides. In gray matter, only MK was significantly lower in the affected spinal cords than in unaffected spinal cords (0.60 ± 0.18 vs. 0.73 ± 0.13, P = 0.0005, Wilcoxon’s signed rank test).

Conclusions

MK values in the spinal cord may reflect microstructural changes and gray matter damage and can potentially provide more information beyond that obtained with conventional diffusion metrics.     

Comparison of the small-world topology between anatomical and functional connectivity in the human brain

We applied graph analysis to both anatomical and functional connectivity in the human brain. Anatomical connectivity was acquired from diffusion tensor imaging data by probabilistic fiber tracking, and functional connectivity was extracted from resting-state functional magnetic resonance imaging data by calculating correlation maps of time series. For the same subject, anatomical networks seemed to be disassortative, while functional networks were significantly assortative. Anatomical networks showed higher efficiency and smaller diameters than functional networks. It can be proposed that anatomical connectivity, as a major constraint of functional connectivity, has a relatively stable and efficient structure to support functional connectivity that is more changeable and flexible.