Friedrich G. Woermann

Language lateralization by Wada test and fMRI in 100 patients with epilepsy

Comparing the determination of language dominance using fMRI with results of the Wada test in 100 patients with different localization-related epilepsies, the authors found 91% concordance between both tests. The overall rate of false categorization by fMRI was 9%, ranging from 3% in left-sided temporal lobe epilepsy (TLE) to 25% in left-sided extratemporal epilepsy. Language fMRI might reduce the necessity of the Wada test for language lateralization, especially in TLE.

Voxel-by-Voxel Comparison of Automatically Segmented Cerebral Gray Matter—A Rater-Independent Comparison of Structural MRI in Patients with Epilepsy

Quantitative evaluation of MRI in patients with epilepsy can give more information than qualitative assessment. Previously developed volume-of-interest-based methods identified subtle widespread structural changes in the neocortex beyond the visualized lesions in patients with malformations of cortical development (MCD) and hippocampal sclerosis (HS) and also in MRI-negative patients with juvenile myoclonic epilepsy (JME). This study evaluates a voxel-based automated analysis of structural MRI in epilepsy. After fully automated segmentation of cerebral gray matter from structural T1-weighted, high-resolution MRI scans, we applied the automated and objective technique of statistical parametric mapping (SPM) to the analysis of gray matter of 35 control subjects, 10 patients with partial seizures and MCD, 10 patients with left temporal lobe epilepsy (TLE) and HS, 10 patients with left TLE and normal MR quantitation of the hippocampus, and 20 patients with JME. At a corrected threshold of P < 0.05, significant abnormalities were found in 3/35 controls; in all 10 patients with MCD, 6 of whom had additional lesions beyond the margins of the visualized abnormalities; in 2/10 TLE patients with HS; in 2/10 MRI-negative TLE; and in 4/20 JME patients. Group comparisons between control subjects and HS patients identified the affected left temporal lobe with an increase in gray matter in the posterior temporal lobe, but did not identify hippocampal atrophy. The group of MRI-negative TLE patients showed no abnormalities compared with control subjects. Group comparison between control subjects and JME patients identified a mesial frontal increase in gray matter. The SPM-based voxel-by-voxel comparison of gray matter distribution identified MCD and abnormalities beyond the visualized lesion in individual MCD patients. The method did not reliably identify HS in individual patients or identify abnormalities in individual MRI-negative patients with TLE or JME in a proportion larger than the chance findings in the control group. Using group comparisons, structural abnormalities in the neocortical gray matter of patients with TLE and HS were lateralized to the affected temporal lobe. In patients with JME as a group, an increase in gray matter was localized to the mesial frontal area, corroborating earlier quantitative MRI findings.

Fast, accurate, and reproducible automatic segmentation of the brain in T1-weighted volume MRI data.

A new fast automated algorithm has been developed to segment the brain from T1‐weighted volume MR images. The algorithm uses automated thresholding and morphological operations. It is fully three‐dimensional and therefore independent of scan orientation. The validity and the performance of the algorithm were evaluated by comparing the automatically calculated brain volume with semi‐automated measurements in 10 subjects, by calculating the brain volume from repeated scans in another 10 subjects, and by visual inspection. The mean and standard deviation of the difference between semi‐automated and automated measurements were 0.56% and 2.8% of the mean brain volume, respectively, which is within inter‐observer variability of the semi‐automated method. The mean and standard deviation of the difference between the total volumes calculated from repeated scans were 0.40% and 1.2% of the mean brain volume, respectively. Good results were also obtained from a scan of abnormal brains. Magn Reson Med 42:127–135, 1999.

Regional changes in hippocampal T2 relaxation and volume: a quantitative magnetic resonance imaging study of hippocampal sclerosis

OBJECTIVE The principal MRI features of hippocampal sclerosis are volume loss and increased T2 weighted signal intensity. Minor and localised abnormalities may be overlooked without careful quantitation. Hippocampal T2 relaxation time (HT2) can be quantified, but previously has only been measured on a few thick coronal slices with interslice gaps. In this study HT2 was measured along the entire length of the hippocampus on contiguous slices and used, with quantitative measures of hippocampal volume (HV) and distribution of atrophy, to better define the range of hippocampal sclerosis. METHODS Thirty patients with temporal lobe epilepsy, 10 patients with extratemporal localisation related epilepsy and extratemporal lesions, and 20 control subjects were studied using MRI T2 relaxometry and volumetry. RESULTS In controls and patients, HT2 was higher in the anterior than the posterior hippocampus. Using HV, morphometric, and HT2 data, patients with temporal lobe epilepsy were classified as unilateral diffuse hippocampal sclerosis (n=16), unilateral focal (n=6), bilaterally affected (n=6), and normal (n=2). In patients with unilateral hippocampal sclerosis, the anterior hippocampus was always affected. In three patients with normal HV, HT2 measurements disclosed unilateral focal abnormalities that corresponded to the EEG lateralisation of epileptic activity. Patients with bilateral hippocampal involvement had an earlier onset of epilepsy than patients with unilateral hippocampal sclerosis. CONCLUSIONS Measurement of regional abnormalities of HT2 along the length of the hippocampus provides further refinement to the MRI assessment of the hippocampi in patients with temporal lobe epilepsy and is complementary to volumetric and morphological data.

Memory fMRI lateralizes temporal lobe epilepsy.

Background: The assessment of mesial temporal lobe (MTL) function is important for the diagnosis and treatment of temporal lobe epilepsy (TLE) and other brain diseases. Declarative memory depends on the integrity of the MTL region. Objective: To investigate hemispheric asymmetries of MTL activity in patients with symptomatic TLE. Methods: With use of blood oxygenation level-dependent fMRI, hemispheric asymmetries in MTL activation of 30 individual patients with refractory symptomatic TLE and 17 healthy control subjects were studied. Activation was induced by a task employing mental navigation and recall of landmarks based on the retrieval of individually familiar visuospatial knowledge. Results: The study demonstrated that the memory task used reliably activated MTL structures in individual control subjects and patients with refractory TLE including children, older subjects, and patients with low formal IQ. Interhemispheric differences in MTL activation lateralized the side of seizure onset in 90% of patients with symptomatic unilateral TLE. In contrast, healthy control subjects did not show a systematic asymmetry of MTL activation. Correlations between MTL activation and neuropsychological measures suggest that the fMRI-detectable MTL changes were specifically related to memory rather than to memory-independent visuospatial abilities. Conclusion: fMRI of memory-induced MTL activation lateralizes the side of seizure onset in patients with refractory symptomatic TLE and may provide complementary information for presurgical evaluation.

Posttraumatic stress disorder and fMRI activation patterns of traumatic memory in patients with borderline personality disorder.

BACKGROUND Early traumatization and additional posttraumatic stress disorder are frequent in patients with borderline personality disorder (BPD). The purpose of this study was to investigate neural correlates of traumatic memory in BPD with and without posttraumatic stress disorder (PTSD) using functional magnetic resonance imaging (fMRI). METHODS We studied 12 traumatized female patients BPD, 6 of them with and 6 without PTSD. According to an autobiographical interview key words (cues) were defined for traumatic and for negative but nontraumatic episodes. In a block-designed fMRI task patients recalled these episodes. Contrasts between trauma condition and nontrauma condition were analyzed. RESULTS Analyses for all subjects revealed activation of orbitofrontal cortex areas in both hemispheres, anterior temporal lobes, and occipital areas. In the subgroup without PTSD, activation of orbitofrontal cortex on both sides and Brocas area predominated. In the subgroup with additional PTSD, we observed right more than left activation of anterior temporal lobes, mesiotemporal areas, amygdala, posterior cingulate gyrus, occipital areas, and cerebellum. CONCLUSIONS Dependent on absence or presence of additional PTSD different neural networks seem to be involved in the traumatic memory of patients with BPD.

Functional organization of the brain with malformations of cortical development

We examined the localization of cerebral functions in 28 patients with focal epilepsy and malformations of cortical development (MCDs). Polymicrogyria occurred in nine, hemimegalencephaly in four, heterotopia in eight, and focal cortical dysplasia (FCD) in nine cases. We used simple (sensomotor, visual) or complex (language, memory) functional magnetic resonance imaging (fMRI) paradigms. Two thirds of MCDs were activated by simple fMRI paradigms, whereas they less frequently showed activity during complex cognitive fMRI paradigms. During simple paradigms, all disturbances of cortical organization (polymicrogyria, schizencephaly, and mild‐type FCD) showed activity, whereas other MCDs (disturbances of earlier steps of cortical development: hemimegalencephaly, Taylor‐type FCD, and heterotopia) showed activity in only 44% (p < 0.01). The association between the pathophysiology and morphology of MCDs confirms the recently proposed classification system. Both focal neurological signs (p < 0.05) and focal electroencephalogram slowing (p < 0.05) independently correlated with MCD inactivity, confirming that fMRI showed neuronal functions of MCDs. Conclusively, fMRI visualizes the MCD functions and their relationship to the eloquent cortex, providing useful information before epilepsy surgery. Surgery of cortical organization disturbances should be cautiously performed because these malformations may participate to some degree in brain functions. Ann Neurol 2003;53:759–767

Short echo time single-voxel 1H magnetic resonance spectroscopy in magnetic resonance imaging-negative temporal lobe epilepsy : Different biochemical profile compared with hippocampal sclerosis

Single‐voxel proton magnetic resonance spectroscopy (1H MRS) has shown abnormalities in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). Many TLE patients, however, do not have HS or other lesions on quantitative magnetic resonance imaging (MRI) (MRI‐negative). Fifteen control subjects, 15 patients with unilateral HS, and 15 MRI‐negative TLE patients underwent 1H MRS at an echo time of 30 msec on a 1.5‐T GE Signa scanner. Voxels were tailored to the individual hippocampi. N‐Acetylaspartate (NAA), creatine, choline, total glutamate plus glutamine (Glx), and myo‐inositol (Ins) were quantitated by using an external standard and LCModel, a user‐independent quantitation method. Normal ranges were defined as the control mean ± 2.5 SD. In HS patients, 12 of 15 had abnormally low NAA in sclerotic hippocampi; 3 of these 12 also had abnormally low NAA contralaterally. Abnormally low NAA/Ins ratios lateralized the side affected by HS in 7 of 15 patients, without any bilateral abnormalities. In 15 MRI‐negative TLE patients, 4 had abnormally low hippocampal NAA ipsilateral to seizure onset, 1 of whom had abnormally low NAA bilaterally. Analysis of groups of subjects showed a bilateral decrease in NAA, most marked in patients with HS and on the side of seizure onset. The mean NAA/Ins ratio was lower in patients with HS than in control subjects and in MRI‐negative patients. The concentration of Glx was higher ipsilateral to seizure onset in MRI‐negative patients than in HS patients. Quantitative short echo time 1H MRS identified abnormalities in 87% of patients with HS and 27% of MRI‐negative TLE patients in concordance with other lateralizing data. In individual and group comparisons, 1H MRS described a metabolite profile in the hippocampi of MRI‐negative TLE patients that was different from patients with HS, with an increase in Glx and a less marked decrease in NAA than was seen in HS. Ann Neurol 1999;45:369–376

Functional MRI Predicts Memory Performance after Right Mesiotemporal Epilepsy Surgery

Summary:  Purpose: Anterior temporal lobe resection (ATR) is a treatment option in drug‐resistant epilepsy. An important risk of ATR is loss of memory because mesiotemporal structures contribute substantially to memory function. We investigated whether memory‐activated functional MRI (fMRI) can predict postoperative memory loss after anterior temporal lobectomy in right‐sided medial temporal lobe epilepsy (MTLE).

Quantitative analysis of short echo time 1H-MRSI of cerebral gray and white matter

Quantitative analysis of 1H‐magnetic resonance spectroscopic imaging (MRSI) data was developed using the user‐independent spectral analysis routine LCModel. Tissue segmentation was performed using statistical parametric mapping software (SPM 96), and the results were used to correct for cerebrospinal fluid contamination. A correction was developed for the imperfections in the spectroscopic excitation profile in order to improve the uniformity of metabolite images. After validation in phantoms, these techniques were applied to study differences in metabolite concentrations between gray and white matter in normal volunteers (n = 13). A positive correlation was found between concentration and gray matter content for most metabolites studied. The estimated ratios of metabolite concentration in gray vs. white matter were: N‐acetyl aspartate + N‐acetyl aspartyl glutamate (NAc) = 1.16 ± 0.11; creatine = 1.7 ± 0.3; glutamate + glutamine = 2.4 ± 0.5; myo‐inositol = 1.6 ± 0.3; choline = 0.9 ± 0.2. The ratio of NAc/Cr was negatively correlated with gray matter content: gray/white = 0.69 ± 0.08. These methods will be useful in the evaluation of metabolite concentrations in MRSI voxels with mixed tissue composition in patient groups. Magn Reson Med 44:401–411, 2000.