White matter abnormalities in children and adolescents with temporal lobe epilepsy

Background and Purpose

The widespread propagation of synchronized neuronal firing in seizure disorders may affect cortical and subcortical brain regions. Diffusion tensor imaging (DTI) can noninvasively quantify white matter integrity. The purpose of this study was to investigate the abnormal changes of white matter in children and adolescents with focal temporal lobe epilepsy (TLE) using DTI.

Materials and Methods

Eight patients with clinically diagnosed TLE and eight age- and sex-matched healthy controls were studied. DTI images were obtained with a 3-T magnetic resonance imaging scanner. The epileptic foci were localized with magnetoencephalography. Fractional anisotropy (FA), mean diffusivity (MD), parallel (λ_||) and perpendicular (λ_⊥) diffusivities in the genu of the corpus callosum, splenium of the corpus callosum (SCC), external capsule (EC), anterior limbs of the internal capsule (AIC), and the posterior limbs of the internal capsule (PIC) were calculated. The DTI parameters between patients and controls were statistically compared. Correlations of these DTI parameters of each selected structure with age of seizure onset and duration of epilepsy were analysed.

Results

In comparison to controls, both patients' seizure ipsilateral and contralateral had significantly lower FA in the AIC; PIC and SCC and higher MD, λ_|| and λ_⊥ in the EC, AIC, PIC and SCC. The MD, λ_|| and λ_⊥ were significantly correlated with age of seizure onset in the EC and PIC. λ_|| was significantly correlated with the duration of epilepsy in the EC and PIC.

Conclusion

The results of the present study indicate that children and adolescents with TLE had significant abnormalities in the white matter in the hemisphere with seizure foci. Furthermore, these abnormalities may extend to the other brain hemisphere. The age of seizure onset and duration of epilepsy may be important factors in determining the extent of influence of children and adolescents TLE on white matter.     

Diffusion properties of cortical and pericortical tissue: regional variations, reliability and methodological issues

Characterizing the diffusion properties of cortical tissue is complicated by intersubject variability in the relative locations of gyri and sulci. Here we extend methods of measuring the average diffusion properties of gyral and sulcal structures after they have been aligned to a common template of cortical surface anatomy. Diffusion tensor image (DTI) data were gathered from 82 young subjects and co-registered with high-resolution T1 images that had been inflated and co-registered to a hemispherically unified spherical coordinate system based on FreeSurfer. We analyzed fractional anisotropy (FA), mean diffusivity (MD) and the novel quantity of cortical primary diffusion direction (cPDD) at five surfaces parallel to the white/gray junction, spanning approximately 5 mm from the pial surface into white matter. FA increased with increasing depth, whereas MD and cPDD were reduced. There were highly significant and reliable regional differences in FA, MD and cPDD as well as systematic differences between cortical lobes and between the two hemispheres. The influence of nearby cortical spinal fluid (CSF), local cortical curvature and thickness, and sulcal depth was also investigated. We found that FA correlated significantly with cortical curvature and sulcal depth, while MD was strongly influenced by nearby CSF. The measurement of FA, MD and cPDD near the cortical surface clarifies the organization of fiber projections to and from the cortex.     

Efficacy of magnetic resonance diffusion tensor imaging and three-dimensional fiber tractography in the detection of clinical manifestations of central nervous system lupus

Systemic lupus erythematosus (SLE) is an autoimmune disease frequently associated with neuropsychiatric manifestations. No follow-up case report has characterized white matter alterations in patients with neuropsychiatric lupus erythematosus (NPSLE) before and after treatment. In this study, a 16-year-old NPSLE patient with severe neuropsychological symptoms was treated with steroid pulse therapy, and was scanned with conventional magnetic resonance (MR) and diffusion tensor imaging (DTI) at onset and 17 months after treatment. Conventional MR images showed diffuse brain atrophy and focal vasogenic edema in the putamen, but they did not reveal abnormalities in the corpus callosum. Region-of-interest analysis of DTI images showed that fractional anisotropy and fiber tracts increased significantly, while axial diffusivity, radial, and mean diffusivity decreased significantly in the corpus callosum after treatment. The results indicated that the vasogenic edema was present in the corpus callosum at onset and was significantly reduced after treatment. These changes were generally compatible with the patient’s clinical manifestations. Hence, we concluded that MR-DTI and fiber tractography are helpful to reveal the relationship between white matter alterations and neurological dysfunctions in NPSLE patients.     

Correlations between microstructural alterations and severity of cognitive deficiency in Alzheimer's disease and mild cognitive impairment: a diffusional kurtosis imaging study

Object

Diffusional kurtosis imaging (DKI), a natural extension of diffusion tensor imaging (DTI), can characterize non-Gaussian diffusion in the brain. We investigated the capability of DKI parameters for detecting microstructural changes in both gray matter (GM) and white matter (WM) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and sought to determine whether these DKI parameters could serve as imaging biomarkers to indicate the severity of cognitive deficiency.

Materials and Methods

DKI was performed on 18 AD patients and 12 MCI patients. Fractional anisotropy, kurtosis and diffusivity parameters in the temporal, parietal, frontal and occipital lobes were compared between the two groups using Mann–Whitney U test. The correlations between regional DKI parameters and mini-mental state examination (MMSE) score were tested using Pearson's correlation.

Results

In ADs, significantly increased diffusivity and decreased kurtosis parameters were observed in both the GM and WM of the parietal and occipital lobes as compared to MCIs. Significantly decreased fractional anisotropy was also observed in the WM of these lobes in ADs. With the exception of fractional anisotropy and radial kurtosis, all the five other DKI parameters exhibited significant correlations with MMSE score in both GM and WM.

Conclusion

Bearing additional information, the DKI model can provide sensitive imaging biomarkers for assessing the severity of cognitive deficiency in reference to MMSE score and potentially improve early detection and progression monitoring of AD based on characterizing microstructures in both the WM and especially the GM.     

Abnormalities of brain neural circuits related to obesity: A Diffusion Tensor Imaging study

PurposeIncreased Body-Mass-Index (BMI) has been associated with brain atrophy in both gray and white matter structures. However, little is known concerning the integrity of white matter tracts in obesity. The purpose of the study was to evaluate the pattern of changes in white matter microstructure in human adiposity.Material and methodsThe study included 268 participants (52 obese, 96 overweight and 120 normal-weight) that were retrospectively evaluated by Diffusion Tensor Imaging. The fractional anisotropy, axial, radial and mean diffusivity values were compared between the above groups using Tract Based Spatial Statistics.ResultsThe analysis revealed that the increased BMI was related with decreased fractional anisotropy in several white matter regions including the anterior and posterior thalamic radiation, the inferior fronto-occipital fasciculus, the inferior and superior longitudinal fasciculus, the corpus callosum (callosal body and forceps minor), the uncinate fasciculus, the internal capsule, the corticospinal tract and the cingulum (cingulate gyrus and hippocampus).ConclusionsAnisotropic diffusion of anatomic regions governing important brain circuits such as reward seeking inhibition, motivation/drive and learning/conditioning decreases with increasing BMI.     

Reduced anisotropy of water diffusion in structural cerebral abnormalities demonstrated with diffusion tensor imaging

We used diffusion tensor imaging (DTI) to investigate the behavior of water diffusion in cerebral structural abnormalities. The fractional anisotropy, a measure of directionality of the molecular motion of water, and the mean diffusivity, a measure of the magnitude of the molecular motion of water, were measured in 18 patients with longstanding partial epilepsy and structural abnormalities on standard magnetic resonance imaging and the results compared with measurements in the white matter of 10 control subjects. Structural abnormalities were brain damage (postsurgical brain damage, nonspecific brain damage, perinatal brain damage, perinatal infarct, ischemic infarct, perinatal hypoxia, traumatic brain damage (n = 3), mitochondrial cytopathy and mesiotemporal sclerosis), dysgenesis (cortical dysplasia (n = 2) and heterotopia) and tumors (meningioma (n = 2), hypothalamic hamartoma and glioma). Anisotropy was reduced in all structural abnormalities. In the majority of abnormalities this was associated with an increased mean diffusivity; however, 30% of all structural abnormalities (some patients with brain damage and dysgenesis) had a normal mean diffusivity in combination with a reduced anisotropy. There was no correlation between fractional anisotropy and mean diffusivity measurements in structural abnormalities (r = -0.1). Our findings suggest that DTI is sensitive for the detection of a variety of structural abnormalities, that a reduced anisotropy is the common denominator in structural cerebral abnormalities of different etiologies and that mean diffusivity and fractional anisotropy may be, in part, independent. Combined measurements of mean diffusivity and fractional anisotropy are likely to increase the specificity of DTI.     

Elevations of diffusion anisotropy are associated with hyper-acute stroke: a serial imaging study

Diffusion tensor imaging (DTI) studies of human ischemic stroke within 24 h of symptom onset have reported variable findings of changes in diffusion anisotropy. Serial DTI within 24 h may clarify these heterogeneous results. We characterized longitudinal changes of diffusion anisotropy by analyzing discrete ischemic white matter (WM) and gray matter (GM) regions during the hyperacute (2.5-7 h) and acute (21.5-29 h) scanning phases of ischemic stroke onset in 13 patients. Mean diffusivity (MD), fractional anisotropy (FA) and T2-weighted signal intensity were measured for deep and subcortical WM and deep and cortical GM areas in lesions outlined by a > or =30% decrease in MD. Average reductions of approximately 40% in relative (r) MD were observed in all four brain regions during both the hyperacute and acute phases post stroke. Overall, 9 of 13 patients within 7 h post symptom onset showed elevated FA in at least one of the four tissues, and within the same cohort, 11 of 13 patients showed reduced FA in at least one of the ischemic WM and GM regions at 21.5-29 h after stroke. The fractional anisotropy in the lesion relative to the contralateral side (rFA, mean+/-S.D.) was significantly elevated in some patients in the deep WM (1.10+/-0.11, n=4), subcortical WM (1.13+/-0.14, n=4), deep GM (1.07+/-0.06, n=1) and cortical GM (1.22+/-0.13, n=5) hyperacutely (< or =7 h); however, reductions of rFA at approximately 24 h post stroke were more consistent (rFA= 0.85+/-0.12).     

Study of pediatric brain development using magnetic resonance imaging of anisotropic diffusion

The properties of water diffusion in human brain tissue can be characterized by diffusion tensors computed from diffusion weighted magnetic resonance images. Since these properties are strongly determined by the structural and geometrical characteristics of the tissue, the maturation process of white matter and gray matter tissue can be expected to be reflected in these images and derived tensor quantities. The purpose of this work was therefore to study the development of pediatric brain in terms of changes occurring in the observed diffusion behavior. Echo planar diffusion tensor imaging was performed on 22 (10 females and 12 males) full term newborn and infant patients, diagnosed in retrospect as neurologically healthy. The subjects were subdivided in three age categories. A number of quantities based on the diffusion images were calculated for each tissue type and age category, and the ability of these quantities to provide sensitive and consistent information about the tissue differences and evolution was evaluated. The results clearly illustrate that the rotationally invariant quantities (e.g., the highest diffusivity, anisotropy ratio and volume ratio) are superior to the rotationally variant ones (e.g., ADCs measured along the three axes of the magnet) often used in the clinic. On the basis of the anisotropy ratio and the volume ratio indices, a correlation between the white matter maturation and the evolution of the diffusion anisotropy could be established. The same quantities did not exhibit any age dependence for the gray matter tissues.     

Is diffusion anisotropy an accurate monitor of myelination?: Correlation of multicomponent T2 relaxation and diffusion tensor anisotropy in human brain

We compare T2-relaxation and diffusion tensor data from normal human brain. The relationships between myelin-water fraction (MWF) and various diffusion tensor measures [e.g., fractional anisotropy (FA), perpendicular diffusivity (ADC perpendicular) and mean diffusivity ] in white matter (WM) and gray matter (GM) structures in the brain were examined in 16 normal volunteers at 1.5 T and 6 normal subjects at 3.0 T and mean diffusivity. We found some degree of linear correlation between these measurements, but by using region of interest (ROI)-based analysis, we also observed several structures which seemed to deviate significantly from a linear relationship. From all investigated relationships between various diffusion tensor measures and myelin-water content, FA and ADC perpendicular yielded the highest correlation coefficients with MWF. However, diffusion anisotropy was also significantly influenced by factors other than myelin-water content. The less operator-dependent voxel-based analysis (VBA) between myelin-water and diffusional anisotropy measures is proposed as an innovative alternative to ROI-based analysis. We confirmed that WM structures, in general, have higher diffusional anisotropy than GM structures and also have higher myelin-water content. However, our findings suggest that in the highly organized fibre arrangement of compact WM structures such as the genu of the corpus callosum, elevated degrees of diffusional anisotropies are measured, which do not necessarily correspond to an elevated myelin content but more likely reflect the highly organized directionality of fibre bundles in these areas (low microscopic and macroscopic tortuosity) as well as strongly restricted diffusion in the interstitial space between the myelinated axons. Conversely, in structures with disorganized fibre bundles and multiple fibre crossings, such as the minor and major forceps, low FA values were measured, which does not necessarily reflect a decrease myelin-water content.     

Comparison of multiple sclerosis clinical subgroups using navigated spin echo diffusion-weighted imaging.

The apparent diffusion coefficient (ADC) of tissue provides an indication of the size, shape, and orientation of the water spaces in tissue. Thus, pathologic differences between lesions in multiple sclerosis (MS) patients with different clinical courses may be reflected by changes in ADC measurements in lesions and white matter. Twelve healthy subjects and 35 MS patients with a relapsing-remitting (n = 10), benign (n = 8), secondary progressive (n = 8) and primary progressive (n = 9) clinical course were studied. T2-weighted and post-gadolinium T1-weighted images were obtained using a 1.5 T Signa Echospeed magnetic resonance imaging (MRI) system. Diffusion-weighted imaging was implemented using a pulsed gradient spin echo (PGSE) sequence with diffusion gradients applied in turn along three orthogonal directions in order to obtain the average apparent diffusion coefficient (ADCav). Navigator echo correction and cardiac gating were used to reduce motion artifact. ADC maps were derived using a two point calculation based on the Stejskal-Tanner formula. Diffusion anisotropy was estimated using the van Gelderen formula to calculate an anisotropy index. MS lesions had a higher ADC and reduced anisotropy compared with normal appearing white matter. Highest ADC values were found in gadolinium enhancing lesions and non-enhancing hypointense lesions on T1-weighted imaging. MS white matter had a slightly higher ADC and lower anisotropy than white matter of healthy subjects. Lesion and white matter ADC values did not differ between patients with different clinical courses of MS. There was no correlation between lesion ADC and disability. Diffusion-weighted imaging with measurement of ADC using the PGSE method provides quantitative information on acute edematous MS lesions and chronic lesions associated with demyelination and axonal loss but does not distinguish between clinical subtypes of MS.