Marc Doelken

In vivo quantification of intracerebral GABA by single-voxel 1H-MRS—How reproducible are the results?

Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human brain. It plays a decisive role in a variety of nervous system disorders, such as anxiety disorders, epilepsy, schizophrenia, insomnia, and many others. The reproducibility of GABA quantification results obtained with a single-voxel spectroscopy J-difference editing sequence with Point Resolved Spectroscopy localization (MEGA-PRESS) was determined on a 3.0 Tesla MR scanner in healthy adults. Eleven volunteers were measured in long- and short-term intervals. Intra- and inter-subject reproducibility were evaluated. Internal referencing of GABA+ to total creatine (tCr) and water (H(2)O), as well as two different post-processing methods for the evaluation (signal integration and time-domain fitting) were compared. In all subjects lower coefficient of variation and therefore higher reproducibility can be observed for fitting compared to integration. The GABA+/tCr ratio performs better than the GABA+/H(2)O ratio or GABA+ without internal referencing for both fitting and integration (GABA+/tCr: 13.3% and 17.0%; GABA+/H(2)O: 15.0% and 17.8%; GABA+: 19.2% and 21.7%). Four-day measurements on three subjects showed higher intra- than inter-subject reproducibility (GABA+/tCr approximately 10-12%). With a coefficient of variation of about 13% for inter-subject and 10-12% for intra-subject variability of GABA+/tCr, this technique seems to be a precise tool that can detect GABA confidently. The results of this study show the reproducibility limitations of GABA quantification in vivo, which are necessary for further clinical studies.

Flat-panel detector volumetric CT for visualization of subarachnoid hemorrhage and ventricles: preliminary results compared to conventional CT

IntroductionThe aim of this study was to compare flat-panel volumetric CT (VCT) to conventional CT (cCT) in the visualization of the extent of subarachnoid hemorrhage (SAH) and the width of the ventricles in patients with acute SAH.MethodsIncluded in the study were 22 patients with an acutely ruptured cerebral aneurysm who received VCT during coil embolization. VCT image quality, the extent of SAH (using a modified Fisher score and total slice number with SAH visible) and the width of the ventricles (Evans index) were evaluated by two experienced neuroradiologists (RAD1 and RAD2) and compared to the findings on cCT. Ten patients undergoing VCT for reasons other than SAH served as negative controls.ResultsInterobserver agreement in rating image quality was excellent for cCT (Kendall W value 0.94) and good for VCT (0.74). SAH was identified by RAD1 and RAD2 on VCT images in all patients. The modified Fisher scores underestimated the extent of SAH on VCT images in comparison with cCT images. Pearson’s correlation coefficient (r) regarding the number of image slices with SAH visible on cCT images compared with the number on VCT images was 0.85 for RAD1 and 0.84 for RAD2. The r value for the degree of interobserver agreement for the number of slices with SAH visible was 0.99 for cCT, and 0.95 for VCT images (n = 19), respectively. The width of the ventricles measured in terms of the Evans Index showed excellent concordance between the modalities (r = 0.81 vs. 0.82).ConclusionOur preliminary results indicate that VCT is helpful in evaluating SAH in the angiography suite. Additionally, reliable evaluation of ventricle width is feasible. However, there are limitations with regard to the visibility of SAH on VCT images in comparison to cCT images.

Visualisation of intracerebral haemorrhage with flat-detector CT compared to multislice CT: results in 44 cases

The aim of the study was to test the reliability of intracerebral haemorrhage (ICH) detection with C-arm-mounted flat-detector computed tomography (FD-CT) in the angio suite as compared to multislice CT (MSCT). In this study 44 patients with 45 ICH were included. All patients were investigated with MSCT and FD-CT during angiographic evaluation. As a control group we included 16 patients without ICH. In each haematoma we assessed volumetric data of the ICH and counted the numbers of ICH-positive slices. Using interobserver ratings, we additionally investigated the potential of FD-CT to serve as a diagnostic tool to detect ICH. In FD-CT three haematomas were not detected because of motion and beam-hardening artefacts in the region close to the skull base. The r value for the degree of interobserver agreement for the number of slices was 0.95 for MSCT and 0.94 for FD-CT. Measurements of the area and the calculated volume of the ICH showed high inter- and intraobserver agreement. Our results indicate that FD-CT is a helpful tool in the daily emergency management of ICH patients as detection of ICH was found to be nearly as reliable as in MSCT. Limitations of this technology are motion and beam-hardening artefacts that may mask small haematomas located in the posterior fossa or the skull base.

Optimized intravenous Flat Detector CT for non-invasive visualization of intracranial stents: first results

ObjectiveAs stents for treating intracranial atherosclerotic stenosis may develop in-stent re-stenosis (ISR) in up to 30%, follow-up imaging is mandatory. Residual stenosis (RS) is not rare. We evaluated an optimised Flat Detector CT protocol with intravenous contrast material application (i.v. FD-CTA) for non-invasive follow-up.MethodsIn 12 patients with intracranial stents, follow-up imaging was performed using i.v. FD-CTA. MPR, subtracted MIP and VRT reconstructions were used to correlate to intra-arterial angiography (DSA). Two neuroradiologists evaluated the images in anonymous consensus reading and calculated the ISR or RS. Correlation coefficients and a Wilcoxon test were used for statistical analysis.ResultsIn 4 patients, no stenosis was detected. In 6 patients RS and in two cases ISR by intima hyperplasia perfectly visible on MPR reconstructions of i.v. FD-CTA were detected. Wilcoxon’s test showed no significant differences between the methods (p > 0.05). We found a high correlation with coefficients of the pairs DSA/ FD-CT MIP r = 0.91, DSA/ FD-CT MPR r = 0.82 and FD-CT MIP/ FD-CT MPR r = 0.8.ConclusionIntravenous FD-CTA could clearly visualise the stent and the lumen, allowing ISR or RS to be recognised. FD-CTA provides a non-invasive depiction of intracranial stents and might replace DSA for non-invasive follow-up imaging.

Clinical evaluation of flat-panel detector compared with multislice computed tomography in 65 patients with acute intracranial hemorrhage: initial results. Clinical article.

OBJECT The goal in this study was to compare flat-panel detector (FD) CT with multislice (MS) CT in the visualization of intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), intraventricular hemorrhage, and external ventricular drains (EVDs) to evaluate the diagnostic quality and limitations of the new FD CT imaging modality. METHODS Neuroimages obtained in 65 patients, including 24 with EVDs, were reviewed by 2 independent, experienced clinicians. Lesions in all patients were investigated with FD CT and MS CT. The numbers of slices positive for ICH and SAH were counted, and for ICH the diameter and area of the lesion was measured. The positioning of drains was assessed. The presence of ventricular blood was noted. Statistical analysis was performed by calculating the Pearson correlation coefficient (r) to evaluate the level of inter- and intraobserver agreement, and linear regression analysis was done to visualize the results of the numbers of ICH- and SAH-positive slices. RESULTS The authors found high interobserver agreement regarding the number of slices with evidence of ICH (r = 0.89 for MS CT, r = 0.78 for FD CT) and SAH (r = 0.88 for MS CT, r = 0.9 for FD CT). Thin layers of blood in the ventricles were not detected on FD CT in 36.4% of cases. Six of 7 perimesencephalic SAHs were not seen on FD CT scans. The EVDs could be assessed with both modalities in 83.3% of cases, but the position of the drain could not be determined with FD CT in 16.7% (4 of 24 cases). CONCLUSIONS In some respects, FD CT is of limited use for the visualization of intracranial hemorrhage. However, despite limited contrast resolution, ICH and EVDs can be reliably demonstrated. Perimesencephalic SAH and thin layers of blood in the occipital horns may not be detected using FD CT. Further evaluation and improvement of the image quality is necessary before FD CT will provide identical quality in comparison with MS CT.

Detection of tumour invasion into the pyramidal tract in glioma patients with sensorimotor deficits by correlation of 18F-fluoroethyl-L-tyrosine PET and magnetic resonance diffusion tensor imaging

PurposeStandard magnetic resonance imaging (MRI) does not depict the true extent of tumour cell invasion in gliomas. We investigated the feasibility of advanced imaging methods, i.e. diffusion tensor imaging (DTI), fibre tracking and O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET, for the detection of tumour invasion into white matter structures not visible in routine MRI.MethodsDTI and fibre tracking was performed on ten patients with gliomas, WHO grades II-IV. Five patients experienced preoperative sensorimotor deficits. The ratio of fractional anisotropy (FA) between the ipsilateral and contralateral pyramidal tract was calculated. Twenty-one stereotactic biopsies from five patients were histopathologically evaluated for the absolute numbers and percentages of tumour cells. 18F-FET PET scans were performed and the bilateral ratio [ipsilateral-to-contralateral ratio (ICR)] of 18F-FET-uptake was calculated for both cross-sections of pyramidal tracts and biopsy sites.ResultsThe FA ratio within the pyramidal tract was lower in patients with sensorimotor deficits (0.61–1.06) compared with the FA ratio in patients without sensorimotor deficits (0.92–1.06). In patients with preoperative sensorimotor deficits, we found a significantly (p = 0.028) higher ICR of 18F-FET uptake (1.01–1.59) than in patients without any deficits (0.96–1.08). The ICR of 18F-FET-uptake showed a strong correlation (r = 0.696, p = 0.001) with the absolute number of tumour cells and a moderate correlation (r = 0.535, p = 0.012) with the percentage of tumour cells.ConclusionsOur data show an association between preoperative sensorimotor deficits, increased 18F-FET uptake and decreased FA ratio in the pyramidal tract. We demonstrated a correlation between tumour invasion and 18F-FET uptake. These findings may help to distinguish between edema versus tumour-associated neurological deficits and could prevent the destruction of important structures, like the pyramidal tract, during tumour operations by allowing more precise preoperative planning.

Flat-detector computed tomography with intravenous contrast material application in experimental aneurysms: Comparison with multislice CT and conventional angiography

Background: Despite limited soft tissue resolution flat-detector computed tomography (FD-CT) provides substantial superior spatial resolution in comparison with multislice computed tomography (MS-CT). This may add value in the visualization of small vascular structures if intravenous contrast application leads to substantial opacification and visibility of intracranial vessels or aneurysms. Purpose: To evaluate the feasibility of visualization of vascular structures by FD-CT angiography (FD-CTA) after intravenous contrast injection compared with MS-CTA and intra-arterial digital subtracted angiography (IADSA) in an animal model. Material and Methods: Aneurysms were created in the right common carotid artery in six New Zealand White Rabbits using the elastase technique. Imaging was performed using FD-CTA, MS-CTA (injection of 1 ml/kg body weight) and IADSA. Anonymized volume rendering reconstruction (VRT), maximum intensity projection (MIP), and multiplanar reconstruction (MPR) images were reconstructed and evaluated by two experienced reviewers for aneurysm geometry and vascular structure anatomy using standard tools of a dedicated workstation. Results: Aneurysms could be successfully created in all animals. Measurements of aneurysm geometry (aneurysm height, width, neck width) and vascular structures (brachiocephalic trunk, carotid artery diameter and plane) were nearly identical in all three modalities. Intra- and inter-observer correlations of the different parameters showed high r values between 0.83 and 0.99. Conclusion: Our results show the feasibility of FD-CTA in comparison with MS-CTA and IADSA in an animal model. Despite limited soft tissue resolution, opacification of vascular structures with sufficient contrast to the surrounding structures was possible in all animals. Vascular structures appeared better delineated in FD-CTA than in MS-CTA, probably due to the superior spatial resolution.

Multi-voxel magnetic resonance spectroscopy at 3 T in patients with idiopathic generalised epilepsy

PURPOSE The objective of our study was to gain further insight into the extent of local metabolic alterations in patients with idiopathic generalised epilepsy (IGE), respectively, the subgroup with generalised tonic-clonic seizures (GTCS). The extent of regional metabolic involvement perhaps indicates the key structures in generation of seizures and involvement of specific network of dysfunction. METHODS Using the multi-voxel technique at a 3 T MRI Scanner metabolite levels of 25 age-matched healthy controls and 18 patients with GTCS were obtained from the basal ganglia, insular cortex, cingulum, hippocampus and along both hemispheres in the fronto-parietal white and grey matter. RESULTS Group analysis of GTCS patients versus healthy controls revealed significant (p < 0.05) decrease of tNAA in the cortex of the central region and cingulum, but also in the thalami. Glx was elevated broadly in both hemispheres, in particular in central region, cingulum, insular cortex and left putamen, yet also in the right thalamus. Cho and mI demonstrated a significant coincidental decrease pronounced in the grey and white matter of the central region. Significant metabolic correlation (p ≤ 0.05) based on tNAA, respectively, Glx occurred between the thalamus and the central region, cingulum, putamen and medial frontal cortex. In patients with > 2 tonic-clonic seizures in the last 12 months a trend towards higher Glx and lower tNAA levels was observed. DISCUSSION Our results demonstrate the altered metabolic interconnection of cerebral anatomic regions in patients with GTCS, in particular the major role of basal ganglia-central region relay in seizure generation.

Alterations of intracerebral γ‐aminobutyric acid (GABA) levels by titration with levetiracetam in patients with focal epilepsies

Purpose:  The objective of this study was to determine if levetiracetam (LEV) modulates brain γ‐aminobutyric acid (GABA) in patients with epilepsy.

1H‐MR Spectroscopy Indicates Severity Markers in Temporal Lobe Epilepsy: Correlations between Metabolic Alterations, Seizures, and Epileptic Discharges in EEG

Summary:  Purpose: In this study, hippocampal metabolite alterations in 1H‐MR spectroscopy (1H‐MRS) were correlated to the findings of intensive video‐EEG monitoring and duration of seizure symptoms in patients with temporal lobe epilepsy (TLE).