Joachim Spreer

Enhanced visualization of blurred gray–white matter junctions in focal cortical dysplasia by voxel-based 3D MRI analysis

PURPOSE Focal cortical dysplasia (FCD), a frequent cause of partial epilepsy, is often associated with blurring of the gray-white matter junction in magnetic resonance images (MRI). To improve the recognition and delineation of FCD we developed a novel voxel-based image post-processing method for enhanced visualization of blurred gray-white matter junctions. METHODS Using standard algorithms of statistical parametric mapping software (SPM99) a T1-weighted MRI volume data set is normalized and segmented. The distribution of gray and white matter is analyzed on a voxelwise basis and compared with a normal database. Based on this analysis, a three-dimensional feature map is created which highlights brain areas with blurred gray-white matter transition. This method was applied to the MRI data of 25 epilepsy patients with histologically proven FCD. RESULTS In 18/25 patients the new feature maps clearly showed that the dysplastic lesions were accompanied by blurring of the gray-white matter junction. Combined with a formerly published method of voxel-based 3D MRI analysis, 21/25 FCD lesions were shown to be associated with either blurring or abnormal extension of gray matter beyond the normal cortical ribbon, including four cases with lesions not or incompletely recognized on conventional MRI. CONCLUSIONS The MRI post-processing presented here improves the visualization of FCD and may increase the diagnostic yield of MRI. Thereby, it provides a valuable additional diagnostic tool in the presurgical evaluation of epilepsy patients.

3D blood flow characteristics in the carotid artery bifurcation assessed by flow-sensitive 4D MRI at 3T

To determine three‐dimensional (3D) blood flow patterns in the carotid bifurcation, 10 healthy volunteers and nine patients with internal carotid artery (ICA) stenosis ≥50% were examined by flow‐sensitive 4D MRI at 3T. Absolute and mean blood velocities, pulsatility index (PI), and resistance index (RI) were measured in the common carotid arteries (CCAs) by duplex sonography (DS) and compared with flow‐sensitive 4D MRI. Furthermore, 3D MRI blood flow patterns in the carotid bifurcation of volunteers and patients before and after recanalization were graded by two independent readers. Blood flow velocities measured by MRI were 31–39% lower than in DS. However, PI and RI differed by only 13–16%. Rating of 3D flow characteristics in the ICA revealed consistent patterns for filling and helical flow in volunteers. In patients with ICA stenosis, 3D blood flow visualization was successfully employed to detect markedly altered filling and helical flow patterns (forward‐moving spiral flow) in the ICA bulb and to evaluate the effect of revascularization, which restored filling and helical flow. Our results demonstrate the feasibility of flow‐sensitive 4D MRI for the quantification and 3D visualization of physiological and pathological flow patterns in the carotid artery bifurcation. Magn Reson Med 61:65–74, 2009.

Determination of hemisphere dominance for language: comparison of frontal and temporal fMRI activation with intracarotid amytal testing

The reliability of frontal and temporal fMRI activations for the determination of hemisphere language dominance was evaluated in comparison with intracarotid amytal testing (IAT). Twenty-two patients were studied by IAT (bilateral in 13, unilateral in 9 patients) and fMRI using a paradigm requiring semantic decisions. Global and regional (frontal and temporoparietal) lateralisation indices (LI) were calculated from the number of activated (r>0.4) voxels in both hemispheres. Frontolateral activations associated with the language task were seen in all patients, temporoparietal activations in 20 of 22. Regional LI corresponded better with IAT results than global LI. Frontolateral LI were consistent with IAT in all patients with bilateral IAT (including three patients with right dominant and one patient with bilateral language representation) and were not conflicting in any of the patients with unilateral IAT. Temporoparietal LI were discordant with IAT in two patients with atypical language representation. In the determination of hemisphere dominance for language, regional analysis of fMRI activation is superior to global analysis. In cases with clear-cut fMRI lateralisation, i.e. consistent lateralised activation of frontal and temporoparietal language zones, IAT may be unnecessary. FMRI should be performed prior to IAT in all patients going to be operated in brain regions potentially involved in language.

Dissociable Contributions of Left and Right Dorsolateral Prefrontal Cortex in Planning

It is well established that the mid-dorsolateral prefrontal cortex (dlPFC) plays a critical role in planning. Neuroimaging studies have yielded predominantly bilateral dlPFC activations, but the existence and nature of functionally specific contributions of left and right dlPFC have remained elusive. In recent experiments, 2 independent parameters have been identified which substantially determine planning: 1) the degree of interdependence between consecutive steps (search depth) and 2) the degree to which the configuration of the goal state renders the order of single steps either clearly evident or ambiguous (goal hierarchy). Thus, search depth affects the actual mental generation and evaluation of action sequences, whereas goal hierarchy reflects the extraction of goal information from an encountered problem. Here, both parameters were independently manipulated in an event-related functional magnetic resonance imaging study using the Tower of London task. Results revealed a double dissociation as indicated by a significant crossover interaction of hemisphere and task parameter: in left dlPFC, activations were stronger for higher demands on goal hierarchy than on search depth, whereas the reversed result emerged in right dlPFC. In conclusion, often observed bilateral patterns of dlPFC activation in complex tasks may reflect the concomitant operation of specific cognitive processes that show opposing lateralizations.

Activation of a residual cortical network during painful stimulation in long-term postanoxic vegetative state: a 15O–H2O PET study

Survivors of prolonged cerebral anoxia often remain in the persistent vegetative state (PVS). In this study, long-term PVS patients were investigated by 15O-H(2)O PET to analyze their central processing of pain. The study was approved by the local Ethics Committee, the experiments were performed in accordance with the Helsinki Declaration of 2000. Seven patients remaining in PVS of anoxic origin for a mean of 1.6 years (range 0.25-4 years) were investigated. We performed functional PET of the brain using 15O-labelled water during electrical nociceptive stimulation. Additionally, a brain metabolism study using 18F-fluorodeoxyglucose (FDG) PET and multi-sequence MRI (including a 3-D data set) were acquired in all patients. PET data were analyzed by means of Statistical Parametric Mapping (SPM99) and coregistered to a study-specific brain template. MRI and FDG PET showed severe cortical impairment at the structural and the functional level, that is, general atrophy of various degrees and a widespread significant hypometabolism, respectively. Pain-induced activation (hyperperfusion) was found in the posterior insula/secondary somatosensory cortex (SII), postcentral gyrus/primary somatosensory cortex (SI), and the cingulate cortex contralateral to the stimulus and in the posterior insula ipsilateral to the stimulus (P<0.05, small-volume-corrected). No additional areas of the complex pain-processing matrix were significantly activated. In conclusion, the regional activity found at the cortical level indicates that a residual pain-related cerebral network remains active in long-term PVS patients.

Detection and Localization of Focal Cortical Dysplasia by Voxel-based 3-D MRI Analysis

Summary:  Purpose: Focal cortical dysplasia (FCD) is a frequent cause of partial epilepsy. Its diagnosis by visual evaluation of magnetic resonance images (MRIs) remains difficult. The purpose of this study was to apply a novel automated and observer‐independent voxel‐based technique for the analysis of 3‐dimensional (3‐D) MRI to detect and localize FCD.

Thalamic gray matter changes in unilateral Parkinsonian resting tremor: a voxel-based morphometric analysis of 3-dimensional magnetic resonance imaging

The thalamus is assumed to be involved in the generation of Parkinsonian tremor. Ten patients with tremor-dominant idiopathic Parkinsons disease (IPD) and strictly unilateral resting tremor were investigated by cerebral high-resolution 3-dimensional magnetic resonance imaging (MRI). MRI data were analyzed by an observer-independent morphometric technique, voxel-based morphometry (VBM). For VBM, MRI data were automatically normalized and segmented, then gray matter volumes were analyzed on a voxel-by-voxel basis in comparison to an age-matched control group using Statistical Parametric Mapping (SPM99). Highly significant structural changes, i.e. locally increased gray matter concentrations (P<0.001), were found in the nucleus ventralis intermedius (VIM) of the thalamus contralateral to the tremor side and were significantly covariant with tremor amplitudes. On the one hand, these changes were localized in close vicinity to a thalamic focal hypermetabolism as revealed by a previous positron emission tomography study in unilateral Parkinsonian tremor patients. On the other hand, the localization of the focal structural changes in VIM corresponds with the generally accepted target area of tremor surgery in IPD.

Remote effects of hippocampal damage on default network connectivity in the human brain

In the healthy human brain the hippocampus is known to work in concert with a variety of cortical brain regions. It has recently been linked to the default network of the brain, with the precuneus being its core hub. Here we studied the remote effects of damage to the hippocampus on functional connectivity patterns of the precuneus. From 14 epilepsy patients with selective, unilateral hippocampal sclerosis and 8 healthy control subjects, we acquired functional MRI data during performance of an object-location memory task. We assessed functional connectivity of a functionally defined region in the precuneus, which showed the typical properties of the default network: significant task-related deactivation, which was reduced in patients compared to control subjects. In control subjects, a largely symmetrical pattern of functional coherence to the precuneus emerged, including canonical default network areas such as ventral medial prefrontal cortex, inferior parietal cortex, and the hippocampi. Assessment of group differences within the default network areas revealed reduced connectivity to the precuneus in ipsilesional middle temporal gyrus and hippocampus in left hippocampal sclerosis patients compared to controls. Furthermore, left hippocampal sclerosis patients showed lower connectivity than right hippocampal sclerosis patients in left middle temporal gyrus, ventral medial prefrontal cortex, and left amygdala. We report remote effects of unilateral hippocampal damage on functional connectivity between distant brain regions associated with the default network of the human brain. These preliminary results underline the impact of circumscribed pathology on functionally connected brain regions.

The reliability of fMRI activations in the medial temporal lobes in a verbal episodic memory task.

The test-retest reliability of activation patterns elicited by encoding and recognition of word-pair associates within the whole brain and a predefined medial temporal region of interest (ROI) was investigated. Twenty healthy right-handed subjects were studied within two sessions, either on the same day or 210-308 days later. Three quantitative measures of reliability were calculated for the contrasts encoding and recognition versus a control condition within the ROI and also for the whole brain: A group correlational analysis between the lateralization indices of the first and second session, correlations of the individual SPM(t) maps of the first and the second run, and overlap ratios between both sessions. For the ROI, correlational analysis of lateralization indices during both encoding trials was significant. Eighty percent of the individual positive correlation coefficients of SPM(t) maps during encoding, and 75% during recognition reached significance. The mean percentage of overlapping voxels was 18% during encoding and 19% during recognition. The reproducibility measures evaluated for the whole brain demonstrated significantly higher values compared to the ROI. For the group that stayed inside the scanner, better whole brain test-retest reliability was observed, and no influence of the memory process (encoding or recognition) on reproducibility was found.

The Brain Tumor Board: Lessons to Be Learned from an Interdisciplinary Conference

Background: The aim of this study is to analyze the work of the interdisciplinary Brain Tumor Board (BTB) which was established at Freiburg University Hospital in 1998. Patients and Methods: From January 1998 to December 2003, a total of 1,516 patients were discussed in 259 meetings of the BTB. The protocols of the BTB were analyzed retrospectively. Results: In 79% of the patients, the diagnosis was based on histological findings or a typical radiological appearance of a lesion, or both. This group was composed of 4 subgroups: 28% benign skull base tumors (19% meningiomas, 4% pituitary adenomas, 3% acoustic schwannomas, 2% others), 24% primary brain tumors of glial origin (8% glioblastomas, 12% gliomas other than glioblastomas, 5% oligoastrocytomas or oligodendrogliomas), 19% brain metastases, and 8% other brain or skull base tumors. In 13% of the cases, the exact diagnosis was still unknown when the patient was presented. 8% of the presentations were motivated by nontumorous interdisciplinary problems (e.g. arterio-venous malformations). The recommendations given by the BTB included: 23% further diagnostic procedures (11% non-invasive examinations, 12% stereotactic biopsies), 57% active antitumoral therapy (22% resection, 17% fractionated radiotherapy, 13% radiosurgery, 5% chemotherapy, <1% embolization), 20% no treatment (14% watchful waiting, 6% supportive care). 91% of the BTB recommendations were realized within 3 months. Conclusion: Interdisciplinary care seems to be particularly necessary in patients with benign skull base tumors, gliomas and brain metastases. Decisions made in a small interdisciplinary group of experts have a high potential of subsequently being realized.