Postictal diffusion weighted imaging.

PURPOSE: Our aim was to determine whether diffusion weighted imaging can detect abnormalities of diffusivity after single seizures, and investigate the localisation and time course of any changes. METHODS: Twenty-one patients with intractable focal epilepsy were imaged interictally and after 23 seizures. Voxel-based statistical parametric mapping was used to detect postictal changes in mean diffusivity (MD), compared to the changes noted in 20 controls scanned twice. The time course and magnitude of the changes were evaluated by measuring MD in the areas of change identified by the voxel-based analysis. RESULTS: Thirty-four focal changes in MD (24 decreases, 10 increases) were detected after 12 of 23 seizures in 11 patients, after a median interval of 53 min from the time of seizure onset. Five patients had areas of both increased and decreased diffusion after seizures. In four patients, postictal changes in diffusion corresponded with the presumed seizure focus. Repeated postictal scanning, after a further interval of a median of 46 min in eight patients, showed that postictal changes in MD, both increases and decreases, were returning towards interictal values. CONCLUSIONS: Diffusion weighted imaging identified focal changes in MD after 52% of single complex partial and secondarily generalised seizures. Changes in MD corresponded to the putative seizure focus in a minority of cases suggesting that the technique is not promising as a method for localising seizure foci, but may indicate the networks involved in seizures.

High-resolution diffusion tensor imaging of the hippocampus in temporal lobe epilepsy.

PURPOSE: To assess the quantitative diffusion characteristics of the hippocampus with high-resolution diffusion tensor imaging (DTI) in temporal lobe epilepsy (TLE). METHODS: Thirteen controls and seven unilateral TLE patients (six with hippocampal sclerosis, one with normal magnetic resonance imaging (MRI)) were scanned with DTI using a zonally magnified oblique multislice echo planar imaging (ZOOM-EPI) acquisition. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in the hippocampi. RESULTS: The mean hippocampal MD ipsilateral to the seizure focus was higher than the contralateral MD in patients (p<0.05) and the mean MD in controls (p<0.001). Hippocampal FA ipsilateral to the seizure focus was lower than the mean FA in controls (p<0.05). MD asymmetry indexes were significantly different between the patient and control groups (p<0.01). All six individual HS patients had ipsilateral hippocampal MD >or=2 standard deviations (S.D.) above the control mean. The patient with normal structural MRI had bilaterally low hippocampal FA and high MD. DISCUSSION: High-resolution DTI identifies lateralizing abnormalities of MD and FA in TLE patients. This quantitative data on hippocampal integrity may assist in evaluating TLE patients with normal MRI, and in longitudinal studies.

Postictal diffusion tensor imaging.

The objective of the study was to investigate postictal diffusion tensor imaging (DTI) in focal epilepsy. DTI and statistical parametric mapping (SPM) were used to examine objectively the diffusion properties of the brains of 18 patients with intractable focal epilepsy both postictally and interictally and to compare them with 27 normal controls scanned twice. Three sets of statistical tests were performed on each patient's fractional anisotropy and mean diffusivity data: interictal versus controls, postictal versus controls and a third "difference analysis" to test for significant changes in comparison with the differences noted between the two sets of control scans. Thirteen of the 18 patients (72%) had significant increases in mean diffusivity in the interictal scan. No decreases in mean diffusivity were detected. The difference analysis detected significant relative decreases in mean diffusivity postictally in nine patients (50%). These changes were focal in seven patients. In six of these, the site of the epileptic focus was known and co-localized with the diffusivity change in three. No significant changes in anisotropy were noted between the post- and interictal states. The postictal decrease in diffusivity probably reflects cellular swelling in the area of seizure onset and possibly areas of seizure spread. Postictal diffusivity changes appear complex and dynamic and timing after the seizure may be critical. Anisotropy measures appear less sensitive to these changes. Further systematic studies are needed and correlation with outcome after epilepsy surgery will determine the role of postictal diffusion measures in the presurgical evaluation of epilepsy patients.

Optimal acquisition orders of diffusion-weighted MRI measurements.

PURPOSE: To propose a new method to optimize the ordering of gradient directions in diffusion-weighted MRI so that partial scans have the best spherical coverage. MATERIALS AND METHODS: Diffusion-weighted MRI often uses a spherical sampling scheme, which acquires images sequentially with diffusion-weighting gradients in unique directions distributed isotropically on the hemisphere. If not all of the measurements can be completed, the quality of diffusion tensors fitted to the partial scan is sensitive to the order of the gradient directions in the scanner protocol. If the directions are in a random order, then a partial scan may cover some parts of the hemisphere densely but other parts sparsely and thus provide poor spherical coverage. We compare the results of ordering with previously published methods for optimizing the acquisition in simulation. RESULTS: Results show that all methods produce similar results and all improve the accuracy of the estimated diffusion tensors significantly over unordered acquisitions. CONCLUSION: The new ordering method improves the spherical coverage of partial scans and has the advantage of maintaining the optimal coverage of the complete scan.

Reorganization of verbal and nonverbal memory in temporal lobe epilepsy due to unilateral hippocampal sclerosis.

PURPOSE: Patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) often suffer from material-specific memory impairments. The purpose of this study was to use functional magnetic resonance imaging (fMRI) to study the organization of specific memory functions in these patients. METHODS: We report 14 patients with unilateral TLE and HS, and 10 controls, performing an fMRI memory paradigm of word, picture, and face encoding. RESULTS: Compared with controls, patients with left TLE demonstrated less left MTL and greater right MTL activation and patients with right TLE demonstrated less right MTL and greater left MTL activation. Correlations between fMRI activation and memory performance revealed greater activation in the damaged left hippocampus to be correlated with better verbal memory performance in left TLE patients and greater right hippocampal activation to be correlated with better nonverbal memory in right TLE patients. Conversely, greater fMRI activation in the contralateral hippocampus correlated with worse memory performance. CONCLUSIONS: Our findings suggest that memory function in unilateral TLE is better when it is sustained by activation within the damaged hippocampus and that reorganization to the undamaged MTL is an inefficient process, incapable of preserving memory function.

Evaluation of quantitative magnetic resonance imaging contrasts in MRI-negative refractory focal epilepsy.

PURPOSE: Conventional optimal MRI is unremarkable in 20%-30% of patients with intractable focal epilepsy. These MRI-negative patients are the most challenging in surgical programs. Our aim was to evaluate the yield and utility of quantitative MRI with novel contrasts in MRI-negative patients with refractory focal epilepsy, who were potential surgical candidates. METHODS: Ninety-three consecutive potential surgical candidates with refractory focal epilepsy, 44 with temporal lobe epilepsy, and 49 with frontal lobe epilepsy as determined with ictal scalp video-EEG; and normal optimal conventional MRI, including hippocampal volumes and T2 measures were investigated with quantitative MRI contrasts. The contrasts comprised fast fluid attenuated inversion recovery based T2 measurement (FFT2), double inversion recovery (DIR), magnetization transfer ratio (MTR), and voxel-based morphometry of gray matter (VBM). Voxel-based analyses of whole brain data were used to compare each patient with a control group. RESULTS: In patients with a putative single focus on scalp video-EEG telemetry, 16% had concordant FFT2 abnormalities, as did 16% with DIR, 5% with MTR and 9% with VBM. The greatest agreement in the localization of abnormalities was between FFT2 and DIR. Altogether, 31% patients had a focal abnormality with at least one contrast in the lobe of seizure onset. Signal changes outside the lobe of the putative focus were found with FFT2 in 36% patients, with DIR in 42%, with MTR in 6% and with VBM in 7%. DISCUSSION: Quantitative analysis of MRI contrasts had a low yield of identifying focal abnormalities concordant with putative epileptic foci in patients with unremarkable conventional MRI. Specificity was low for FFT2 and DIR. With the low specificity, data must be interpreted with caution, but in some patients may assist in creating a hypothesis for testing with intracranial electrodes.

Abnormalities of language networks in temporal lobe epilepsy.

Functional magnetic resonance imaging (fMRI) in patients with temporal lobe epilepsy (TLE) has demonstrated reorganisation of language functions with greater involvement of the non-dominant hemisphere. The structural brain connections supporting this atypical language dominance have not previously been identified. We performed fMRI of language functions and imaging of white matter connections using MR tractography in 14 patients with unilateral TLE and hippocampal sclerosis and 10 controls. Verb generation and reading comprehension paradigms were used to define functional regions which were used to generate starting regions for tractography. Controls and right TLE patients had a left-lateralised pattern of both language-related activations and the associated structural connections. Left TLE patients showed more symmetrical language activations, along with reduced left hemisphere and increased right hemisphere structural connections. Subjects with more lateralised functional activation had also more highly lateralised connecting pathways. We provide evidence for structural reorganisation of white matter tracts that reflects the altered functional language lateralisation in left TLE patients. The combination of fMRI and tractography offers a promising tool for studying the reorganisation of language functions in many neurological conditions and may prove useful in predicting language deficits following temporal lobe surgery.

Imaging the neocortex in epilepsy with double inversion recovery imaging.

The neocortices of 10 patients with partial seizures and acquired lesions, 14 patients with malformations of cortical development (MCD) and 33 patients with partial seizures and normal conventional MRI were quantitatively evaluated using whole brain double inversion recovery imaging (DIR) and Statistical Parametric Mapping (SPM). Compared to a group of 30 control subjects, DIR and objective voxel-by-voxel statistical comparison identified regions of significantly abnormal DIR signal intensity (DSI) in 9 out of 10 patients with acquired nonprogressive cerebral lesions and partial seizures. In all 9 patients, the areas of abnormal DSI concurred with abnormalities identified on visual inspection of conventional MRI. In all 14 patients with MCD, SPM detected regions of significantly abnormal DSI; all of which corresponded to abnormalities identified on visual inspection of conventional MRI. In addition, in both groups, there were areas that were normal on conventional imaging, which demonstrated abnormal DSI. Voxel-by-voxel statistical analysis identified significantly abnormal DSI in 15 of the 33 patients with cryptogenic focal epilepsy. In 10 of these, the areas of abnormal DSI concurred with epileptic EEG abnormality and clinical seizure semiology. Group analysis of MRI-negative patients with electroclinical seizure onset localising to the left temporal and left and right frontal regions revealed significantly abnormal DSI within the white matter of each respective lobe. DIR analysed using SPM was sensitive in patients with MCDs and acquired cerebral damage. Significant abnormalities in DSI in individual and grouped MRI-negative patients suggest that occult epileptogenic cerebral lesions are associated with subtle structural abnormalities. DIR is, therefore, a useful quantitative MRI technique for characterising epileptic foci and may contribute to presurgical evaluation.

Hemispheric asymmetries in language-related pathways: a combined functional MRI and tractography study.

Functional lateralization is a feature of human brain function, most apparent in the typical left-hemisphere specialization for language. A number of anatomical and imaging studies have examined whether structural asymmetries underlie this functional lateralization. We combined functional MRI (fMRI) and diffusion-weighted imaging (DWI) with tractography to study 10 healthy right-handed subjects. Three language fMRI paradigms were used to define language-related regions in inferior frontal and superior temporal regions. A probabilistic tractography technique was then employed to delineate the connections of these functionally defined regions. We demonstrated consistent connections between Broca's and Wernicke's areas along the superior longitudinal fasciculus bilaterally but more extensive fronto-temporal connectivity on the left than the right. Both tract volumes and mean fractional anisotropy (FA) were significantly greater on the left than the right. We also demonstrated a correlation between measures of structure and function, with subjects with more lateralized fMRI activation having a more highly lateralized mean FA of their connections. These structural asymmetries are in keeping with the lateralization of language function and indicate the major structural connections underlying this function.

Three-dimensional quantitative magnetisation transfer imaging of the human brain.

Quantitative magnetisation transfer (MT) analysis is based on a two-pool model of magnetisation transfer and allows important physical properties of the two proton pools to be assessed. A good signal-to-noise ratio (SNR) for the measured signal is essential in order to estimate reliably the parameters from a small number of samples, thus prompting the use of a sequence with high SNR, such as a three-dimensional spoiled gradient acquisition. Here, we show how full brain coverage can be accomplished efficiently, using a three-dimensional acquisition, in a clinically acceptable time, and without the use of large numbers of slice-selective radio-frequency pulses which could otherwise confound analysis. This acquisition was first compared in post mortem human brain tissue to established two-dimensional acquisition protocols with differing SNR levels and then used to collect data from six healthy subjects. Image data were fitted using the two pool model and showed negligible residual deviations. Quantitative results were assessed in several brain locations. Results were consistent with previous single-slice data, and parametric maps were of good quality. Further investigations are needed to interpret the regional variation of quantitative MT quantities.

Exploring white matter tracts in band heterotopia using diffusion tractography.

Band heterotopia is a malformation of cortical development characterized by bands of gray matter in the white matter parallel to the surface of the neocortex. Histopathological studies have suggested that small white matter tracts pass through the heterotopia, and functional magnetic resonance imaging studies have shown activation in the malformation. We used diffusion tractography to explore the anatomical connectivity of band heterotopia and, in particular, whether in vivo white matter tracts traverse the heterotopic gray matter. Five patients with band heterotopia and five control subjects were scanned with whole brain diffusion tensor imaging. Anisotropy maps were calculated. Using fast marching tractography, we produced maps of connectivity and tract traces from two seed points, in the splenium of the corpus callosum and the right parietal lobe. Eigenvectors were found to pass through the band heterotopia in an aligned fashion. Patterns for maps of connectivity were similar in patients and control subjects. Areas of high connectivity were found in the band heterotopia and in cortical areas on the far side of the malformation from the seed point. The tracts hence appeared to traverse or end within the band heterotopia. The results are in agreement with previous histopathological studies and indicate the structural basis of the functional connectivity and absence of focal deficits in these patients.