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Biomedical subjects

F G Woermann

Publications and source records attributed to F G Woermann.

At least 37 records · Page 2Linked to original sources
PubMed2001

Neuropathological abnormalities in schizophrenia: evidence from magnetization transfer imaging.

Post-mortem and structural brain imaging studies in schizophrenia have reported macroscopic changes such as global and regional cortical volume reductions, but it has been more difficult to characterize the histopathological changes that underlie these abnormalities. Magnetization transfer imaging (MTI), a novel MRI technique, more sensitive to subtle or early neuropathological changes than conventional MRI, provides a quantitative measure of macromolecular structural integrity represented by the magnetization transfer ratio (MTR). In this study, we used MTI to examine 25 patients with schizophrenia compared with 30 age-matched controls. A voxel-based analysis of the MTR maps revealed widespread MTR reductions in the cortex unrelated to volume reduction, predominantly in the frontal and temporal regions, in the schizophrenic patients when compared with controls. MTR reductions in bilateral parieto-occipital cortex and the genu of the corpus callosum were associated with the severity of negative symptoms in the schizophrenic patients. However, MTR changes were not related to other clinical variables of age, duration of illness and current dose of antipsychotic medication. This study demonstrates that MTR abnormalities in the cortex can be detected in chronic schizophrenia that may reflect subtle neuropathological changes involving neurones or neuronal processes. Longitudinal studies are needed to determine whether these abnormalities are related to disease progression or other disease manifestations such as cognitive changes.

Adult↗
PubMed2000

11C-flumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI.

BACKGROUND: Using 11C-flumazenil (FMZ) PET with correction for partial-volume effect, reductions of central benzodiazepine receptor (cBZR) binding can be detected reliably in vivo on remaining neurons in sclerotic hippocampi of patients with mesial temporal lobe epilepsy (TLE). OBJECTIVE: To delineate abnormalities of 11C-FMZ binding in patients with medically refractory TLE and normal quantitative MRI. METHODS: Analysis of parametric images of FMZ volume of distribution (Vd) using two complementary approaches: 1) MRI-based volume of interest (VOI) approach with partial volume effect correction for multiple hippocampal and extrahippocampal VOIs; and 2) statistical parametric mapping (SPM) to localize significant 11C-FMZ binding changes objectively on a voxel-by-voxel basis. RESULTS: Significant abnormalities of absolute FMZ-Vd were found after partial volume effect correction in 5 of 10 patients: unilateral decrease in the amygdala ipsilateral to the EEG focus (1), unilateral hippocampal decreases and bilateral temporal and extratemporal neocortical decreases (2), unilateral increase in the temporal neocortex together with extratemporal neocortical increases (1), and bilateral posterior hippocampal increases together with temporal neocortical increases (1). In the three patients with extratemporal neocortical changes, the concomitant unilateral hippocampal or temporal neocortical changes were contralateral to the presumed epileptic focus. Significant asymmetries of FMZ-Vd between homologous regions were found in six patients. In four of those patients, absolute FMZ-Vd for the homologous regions were within normal limits, with two of the four patients showing relatively higher hippocampal values ipsilateral to the presumed epileptic focus. SPM analysis localized significant abnormalities of FMZ-Vd in similar locations in three of the seven patients in whom VOI analysis detected significant changes. In addition, SPM indicated significant unilateral contralateral hippocampal decreases in an eighth patient. However, both methods failed to localize epileptic foci in two patients identified by depth-EEG recordings. CONCLUSIONS: 11C-FMZ PET showed focal increases as well as decreases of FMZ binding in 80% of patients with refractory TLE and normal high-quality MRI but was not consistently helpful in localizing the epileptic foci.

Adult↗
PubMed2000

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

Quantitative analysis of (1)H-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.

Adult↗
PubMed2000

Affective aggression in patients with temporal lobe epilepsy: a quantitative MRI study of the amygdala.

Recurrent episodes with interictal affective aggression are a rare but well-recognized problem in patients with temporal lobe epilepsy. They are referred to as episodic dyscontrol or, more precisely, as intermittent explosive disorder (IED). The amygdala play a crucial role in the affective evaluation of multimodal sensory input and the neurobiological mediation of aggressive behaviour. With hippocampal sclerosis, in the context of mesial temporal lobe sclerosis, being the most common cause of temporal lobe epilepsy, we hypothesized that the amygdala might be affected by the same pathogenic process in aggressive patients. We investigated 50 patients with temporal lobe epilepsy: 25 with and 25 without a history of IED. Data from clinical, electrophysiological, neuropsychological and psychometric investigations were obtained, as well as MRI scans for the quantitative assessment of possible amygdala pathology. We found no evidence of a higher prevalence of amygdala sclerosis in the aggressive patients. Hippocampal sclerosis was significantly less common in patients with temporal lobe epilepsy and IED. However, a significant subgroup of patients (20%) with temporal lobe epilepsy and aggressive behaviour had severe amygdala atrophy in the context of a history of encephalitis. Another subgroup of aggressive patients (28%) had different left temporal lesions affecting either the amygdala or periamygdaloid structures. IED was associated with left-sided or bilateral EEG and MRI abnormalities, low IQ and high scores in depression and anxiety.

Adolescent↗
PubMed2000

Reduction of frontal neocortical grey matter associated with affective aggression in patients with temporal lobe epilepsy: an objective voxel by voxel analysis of automatically segmented MRI.

BACKGROUND: Interictal episodes of aggression are often reported in patients with epilepsy. Some have characteristics of what has been referred to as episodic dyscontrol or intermittent explosive disorder (IED). Although structural brain abnormalities are thought to play a part in the pathophysiology of aggression, there are few in vivo studies of structural cerebral changes in patients with epilepsy and aggression. Using quantitative MRI, subtle structural brain abnormalities can be investigated in subgroups of patients with both epilepsy and episodes of affective aggression. METHODS: After automated segmentation of cerebral grey matter from T1 weighted MRI, the objective technique of statistical parametric mapping (SPM) was applied to the analysis of 35 control subjects, 24 patients with temporal lobe epilepsy (TLE) with a history of repeated, interictal episodes of aggression, and 24 patients with TLE without episodes of aggression. Both TLE patient groups were compared with each other and with the control subjects on a voxel by voxel basis for increases and decreases of grey matter. RESULTS: The patients with TLE with aggressive episodes had a decrease of grey matter, most markedly in the left frontal lobe, compared with the control group and with patients with TLE without aggressive episodes. CONCLUSION: These findings suggest that a reduction of frontal neocortical grey matter might underly the pathophysiology of aggression in TLE. These voxel by voxel comparisons can guide further in vivo studies into aggression.

Adolescent↗
PubMed1999

Amygdala enlargement in dysthymia--a volumetric study of patients with temporal lobe epilepsy.

BACKGROUND: Previous studies indicated an important role of the amygdala for emotional information processing. We investigated a possible relationship between amygdala volumes, aggressive behavior, and dysthymia, in patients with temporal lobe epilepsy (TLE). METHODS: Patients with TLE with and without aggression or dysthymia and healthy volunteers were assessed using quantitative MRI. Amygdala volumes were measured in a blinded fashion and corrected for total brain volumes. RESULTS: There was a highly significant enlargement of left and right amygdala volumes in patients with dysthymia (right side, p < .000; left side, p = .001). We found a significant positive correlation between left amygdala volumes (p = .02) and a trend towards positive correlation between right amygdala volumes and depression (p = .06), as measured with the Beck Depression Inventory. Amygdala volumes of females were significantly larger than those of males (left side: p = .005; right side: p = .06). CONCLUSIONS: This is the second report of a relationship between amygdala volumes and depressed mood, confirming an earlier finding in patients with bipolar disease, and the first study reporting a correlation between amygdala volumes and depression. Increased processing of emotional information might increase amygdala blood flow and subsequently, result in amygdala enlargement.

Adolescent↗
PubMed1999

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.

Adult↗
PubMed1999

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.

Adult↗
PubMed1999

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.

Adolescent↗
PubMed1999

Reproducible localization of interictal epileptiform discharges using EEG-triggered fMRI.

We report preliminary experiences using fMRI triggered by EEG to localize the site of interictal epileptiform activity. EEG was recorded in the scanner and monitored on-line; the recording quality was good enough to allow the clear identification of spikes in the EEG. Snap-shot EPI was performed 2-4 s after an epileptiform discharge ('spike') or after at least 10 s of background activity ('rest') was observed. A pixel-by-pixel t-test was performed between the 'rest' and the 'spike' images to determine areas of significant activation. Significant activation was obtained in a patient with epilepsy. To assess the reliability and reproducibility of the technique, the patient was scanned on four separate occasions with similar areas being activated in all the studies, confirming the validity of the result.

Brain↗
PubMed1999

Abnormal cerebral structure in juvenile myoclonic epilepsy demonstrated with voxel-based analysis of MRI.

MRI scans of patients with idiopathic generalized epilepsy (IGE) are normal on visual assessment. Using an interactive anatomical segmentation technique and volume-of-interest measurements of MRI, we showed recently that patients with IGE had significantly larger cortical grey matter than control subjects. Further, 40% of individual patients with juvenile myoclonic epilepsy (JME), a syndrome of IGE in adolescence, had significant abnormalities of cerebral structure. In this study, we applied the automated and objective technique of statistical parametric mapping (SPM) to the analysis of structural MRI from 20 patients with JME and 30 control subjects. The cortical grey matter of each individual JME patient and the group of JME patients was contrasted with that of the group of 30 normal subjects. The voxel-based SPM comparison between the group of JME patients and the control subjects showed an increase in cortical grey matter in the mesial frontal lobes of the patients. Analysis of individual patients revealed significant abnormalities of cortical grey matter in five out of 20 JME patients, four of whom had been shown to have widespread abnormalities using the previous volume of interest technique. These findings indicate a structural cerebral abnormality in JME, with involvement of mesiofrontal cortical structures.

Adolescent↗
PubMed1999

EEG-triggered functional MRI of interictal epileptiform activity in patients with partial seizures.

EEG-triggered functional MRI (fMRI) offers the potential to localize the generators of scalp EEG events, such as interictal epileptiform discharges, using a biological measurement as opposed to relying solely on modelling techniques. Although recent studies have demonstrated these possibilities in a small number of patients, wider application has been limited by concerns about patient safety, severe problems due to pulse-related artefact obscuring the EEG trace, and lack of reproducibility data. We have systematically studied and resolved the issues of patient safety and pulse artefact and now report the application of the technique in 24 experiments in 10 consecutive patients with localization-related epilepsy and frequent interictal epileptiform discharges (spikes or spike wave). At least two experiments were performed for each patient. In each experiment, 10- or 20-slice snapshot gradient-echo planar images were acquired approximately 3.5 s after a single typical epileptiform discharge (activation image) and in the absence of discharges (control image). Between 21 and 50 epileptiform discharges were sampled in each experiment. The significance of functional activation was tested using the t test at 95% confidence on a pixel-by-pixel basis. Six of the 10 patients showed reproducible focal changes of the blood oxygen level-dependent (BOLD) signal, which occurred in close spatial relationship to the maximum of the epileptiform discharges in the concurrent EEG. No reproducible focal BOLD signal changes were observed in the remaining four patients. In conclusion, EEG-triggered fMRI is now a sufficiently developed technique to be more widely used in clinical studies, demonstrating that it can reproducibly localize the brain areas involved in the generation of spikes and spike wave in epilepsy patients with frequent interictal discharges.

Adult↗
PubMed1999

Multimodal MR imaging: functional, diffusion tensor, and chemical shift imaging in a patient with localization-related epilepsy.

PURPOSE: To demonstrate the integration of complementary functional and structural data acquired with magnetic resonance imaging (MRI) in a patient with localization-related epilepsy. METHODS: We studied a patient with partial and secondarily generalized seizures and a hemiparesis due to a malformation of cortical development (MCD) in the right hemisphere by using EEG-triggered functional MRI (fMRI), diffusion tensor imaging (DTI), and chemical shift imaging (CSI). RESULTS: fMRI revealed significant changes in regional blood oxygenation associated with interictal epileptiform discharges within the MCD. DTI showed a heterogeneous microstructure of the MCD with reduced fractional anisotropy, a high mean diffusivity, and displacement of myelinated tracts. CSI demonstrated low N-acetyl aspartate (NAA) concentrations in parts of the MCD. CONCLUSIONS: The applied MR methods described functional, microstructural, and biochemical characteristics of the epileptogenic tissue that cannot be obtained with other noninvasive means and thus improve the understanding of the pathophysiology of epilepsy.

Adult↗
PubMed1998

Identifying homologous anatomical landmarks on reconstructed magnetic resonance images of the human cerebral cortical surface.

Guided by a review of the anatomical literature, 36 sulci on the human cerebral cortical surface were designated as homologous. These sulci were assessed for visibility on 3-dimensional images reconstructed from magnetic resonance imaging scans of the brains of 20 normal volunteers by 2 independent observers. Those sulci that were found to be reproducibly identifiable were used to define 24 landmarks around the cortical surface. The interobserver and intraobserver variabilities of measurement of the 24 landmarks were calculated. These reliably reproducible landmarks can be used for detailed morphometric analysis, and may prove helpful in the analysis of suspected cerebral cortical structured abnormalities in patients with such conditions as epilepsy.

Anatomy, Regional↗
PubMed1998

Quantitative MRI in patients with idiopathic generalized epilepsy. Evidence of widespread cerebral structural changes.

In patients with idiopathic generalized epilepsy (IGE), visual inspection of routine MRI is normal. However, pathological studies have shown microdysgenesis in grey and white matter in a large percentage of autopsies from cases of IGE. Recently, widespread structural changes not evident on visual inspection of high resolution MRI have been shown using quantitative MRI in patients with apparently focal cerebral dysgenesis. We sought to determine whether similar quantitative changes might be present in patients with IGE, reflecting possible underlying structural abnormalities. Twenty patients with juvenile myoclonic epilepsy, 10 patients each with childhood absence epilepsy and juvenile absence epilepsy, five patients with tonic-clonic seizures on awakening and 30 control subjects had T1-weighted volume acquisition MRI scans on a 1.5T GE scanner. The cerebral hemispheres were segmented semi-automatically, allowing the comparison of normalized cortical and subcortical matter volumes between groups, and investigation of the regional distribution of cortical and subcortical matter in individual subjects. Patients with IGE had significantly larger cortical grey matter volumes than control subjects. Significant abnormalities of the regional distribution of cerebral grey and subcortical matter were found in eight out of 20 patients with juvenile myoclonic epilepsy, one out of 10 patients with childhood absence epilepsy, four out of 10 patients with juvenile absence epilepsy and two out of five patients with tonic-clonic seizures on awakening, but in none of the 30 control subjects. Using MRI-segmentation, we identified widespread cerebral structural changes in patients with various IGE syndromes. Quantitative MRI supports the existence of structural abnormalities in patients with IGE.

Adolescent↗
PubMed1998

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.

Adult↗