Thilo Hammen

Diffusion tensor imaging and optimized fiber tracking in glioma patients: Histopathologic evaluation of tumor-invaded white matter structures

Fiber tracking is increasingly used to plan and guide neurosurgical procedures of intracranial tumors in the vicinity of functionally important areas of the brain. However, valid data concerning the reliability of tracking with respect to the actual pathoanatomical situation are lacking. We retrospectively correlated fiber tracking based on magnetic resonance (MR) DT imaging with the histopathological data of 25 patients with WHO grade II and III gliomas. Fiber tracking using the Fiber Assignment by Continuous Tracking (FACT) method was performed to investigate the integrity of white matter tracts in the surrounding border zone of the lesions. The tracking procedure was stopped when fractional anisotropy (FA) thresholds = 0.1, 0.15, 0.2, 0.25, and 0.3, or a tract turning angle >60 degrees were encountered. In 9 patients we were able to reconstruct brain fiber tracts at biopsy loci (2-32% tumor infiltration) using an FA threshold of 0.15 and 0.2, but not for a threshold of 0.25 or 0.3. The neurological outcome demonstrated potential tumor cell infiltration of functionally intact brain fiber tracts in the range of 2-8%. These findings may be useful in planning therapeutic approaches to gliomas in the vicinity of eloquent brain regions.

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.

Age-related degradation in the central nervous system: assessment with diffusion-tensor imaging and quantitative fiber tracking.

PURPOSE To prospectively quantify differences in age-related changes in the diffusivity parameters and fiber characteristics between association, callosal, and projection fibers. MATERIALS AND METHODS This study was approved by the institutional review board, and informed consent was obtained. Diffusion-tensor imaging data with an isotropic voxel size of 1.9 mm(3) were acquired at 3 T in 38 healthy volunteers (age range, 18-88 years; 18 women). Quantitative fiber tracking was used to calculate fractional anisotropy (FA) and mean diffusivity values, eigenvalues (lambda(1), lambda(2), and lambda(3)), the number of fiber projections, and the number of fiber projections per voxel for three-dimensional reconstructed association, callosal, projection, and total brain fibers. Bivariate linear regression models were used to analyze correlations. Significant differences between correlations were assessed with the Hotelling-Williams test. RESULTS For FA, the strongest degradation in association fibers and no significant changes in projection fibers were observed. The difference in correlation was significant (P = .002). The number of fiber projections and the number of fiber projections per voxel showed strong to moderate negative correlations that were dependent on age (P < .001) in the three fiber structures and total brain fibers, with the exception of the number of fiber projections per voxel in projection fibers, which showed no significant correlation. The decrease in the number of fiber projections was significantly greater (P = .043) in projection fibers than in total brain fibers, whereas the decrease in the number of fiber projections per voxel was significantly weaker (P = .005). Association fibers showed the largest changes per decade of age for FA (-1.13%) and for the number of fiber projections per voxel (-4.7%), whereas callosal fibers showed the largest changes per decade of age for the number of fiber projections (-10.4%). CONCLUSION Quantitative fiber tracking enables identification of differences in diffusivity and fiber characteristics due to normal aging.

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.

Prediction of postoperative outcome with special respect to removal of hemosiderin fringe: A study in patients with cavernous haemangiomas associated with symptomatic epilepsy

PURPOSE In this study 30 patients with symptomatic epilepsy caused by cavernomas were investigated in a postoperative follow up study to assess predictors for postoperative outcome with respect to indications, time and approach of surgery. METHODS Thirty patients with cavernomas refractory to medical treatment were scheduled for surgery based on the findings of high-resolution MR imaging and intensive EEG-video monitoring. Postoperative outcome of epilepsy was assessed by follow-up examinations based on the basis of classification by Engel and the International League against epilepsy (ILAE). RESULTS The following variables were associated with good postoperative outcome: (1) complete resection of hemosiderin fringe surrounding the cavernoma was correlated to less postoperative seizure frequency versus incomplete resection of the hemosiderin fringe according to the outcome protocol of ILAE. (2) Lower duration of epilepsy at the time of operation was correlated to a better postoperative outcome with a benefit for recovery. (3) Absence of hemorrhage before surgery and unifocal seizure onset was a predictor for a favorable outcome, whereas bilateral or multifocal seizure onset zones showed poorer postoperative outcomes. (4) In patients with dual pathology (hippocampal sclerosis in addition to a cavernoma), lesionectomy plus hippocampectomy as opposed to lesionectomy only, had a better outcome than single lesionectomy. CONCLUSION Postoperative outcome in patients with cavernomas should be the topic of further prospective multicenter studies involving a large number of patients. In addition to the ideal operation time and handling of dual pathology the role of extended resection including perilesional hemorrhages should be taken into account.

Proton Magnetic Resonance Spectroscopic Imaging in the Border Zone of Gliomas: Correlation of Metabolic and Histological Changes at Low Tumor Infiltration—initial Results

Purpose:We sought to retrospectively investigate differences in correlation of absolute metabolites concentrations and metabolite ratios with histopathologic parameters of stereotactic biopsies from the border zone of gliomas. Materials and Methods:Proton magnetic resonance spectroscopic imaging (1H-MRSI) with high spatial resolution was performed in 10 glioma patients at 1.5 T. Magnetic resonance spectroscopic imaging (MRSI) data were coregistered to a 3D MR data set used for stereotactic procedures. Metabolite concentrations of choline-containing compounds (Cho), creatine (Cr), and total N-acetyl-aspartate (tNAA) in addition to metabolite ratios of Cho/Cr, tNAA/Cr, and Cho/tNAA were calculated for voxel positions at biopsy loci with low tumor cell infiltration. Metabolite values were correlated with histopathologic findings expressed as a relative (% tumor infiltration, %TI) and an absolute parameter (tumor cell number, TCN). Results:We found a strong negative linear correlation for tNAA with %TI (R = −0.773, P < 0.001) and TCN (R = −0.769, P < 0.001) but no correlation for Cho (P > 0.05). On the other hand, the metabolite ratio of Cho/Cr showed a moderate positive linear correlation with %TI (R = 0.523, P = 0.012) and TCN (R = 0.486, P = 0.019), but no correlation was obtained for tNAA/Cr (P > 0.05). Differences in correlation between tNAA and Cho as well as tNAA/Cr and Cho/Cr were significant for both %TI (P = 0.012 and P = 0.024) and TCN (P = 0.016 and P = 0.040) using a t test. Conclusions:We conclude that absolute values of tNAA are more significant than Cho in the detection of low tumor cell infiltration. On the basis of absolute metabolite values, neuronal damage seems to be more distinct than cell membrane proliferation in the border zone of gliomas. Furthermore, the calculation of metabolite ratios versus Cr for the border zone may yield to misleading results because Cr is not constant in this area.

Clinical applications of 1H-MR spectroscopy in the evaluation of epilepsies – What do pathological spectra stand for with regard to current results and what answers do they give to common clinical questions concerning the treatment of epilepsies?

Nuclear magnetic resonance spectroscopy (1H‐MRS) is a non‐invasive method in detecting abnormal spectra of various brain metabolites containing N‐acetylaspartate (NAA), Choline (Cho), Creatine (Cr), γ‐Aminobutyric acid (GABA) and Glutamate. Technical processing of the MR‐systems, improved automated shimming methods and further development of special shim coils increase the magnetic field homogeneity and lead to a better spectral quality and spectral resolution. The handling of the systems becomes more user‐friendly and is more likely to be used in routine diagnostics. The 1H‐MRS has become a diagnostic tool for assessing a number of diseases of the central nervous system mainly including epilepsies and brain tumours. The role of 1H‐MRS in the assessment of epilepsies will probably increase in future. In the following article, the principles of 1H‐MRS and an overview of it in the evaluation and treatment of epilepsies with special regard to temporal lobe epilepsies (TLE) has been illustrated.

Periventricular nodular heterotopia: A challenge for epilepsy surgery

Pharmacoresistant focal epilepsies due to periventricular nodular heterotopia are a diagnostic and therapeutic challenge because of the need of invasive presurgical diagnostics and the selection of an optimal surgical approach. Invasive investigations in previous studies showed that focal epileptic activity can be correlated predominantly either with one of the nodular heterotopia or with neocortical epileptogenic zones distant to the periventricular nodules. Up to now, invasive recordings were required for localization of epileptic activity and its correlation to heterotopia. The following case presentation reports on a non-invasive approach using magnetic source imaging (MSI) combined with intraoperative ECoG. MSI combines preoperative data from magnetic resonance imaging (MRI) with magnetoencephalography (MEG). The MSI data for definition of the localization of the epileptic activity and functional important areas were coregistered with the intraoperative high-field-MRI and diffusion tensor imaging-based fiber tracking (DTI) of the visual pathway using a neuronavigational system. A neuronavigation-guided surgical resection of the epileptogenic area was performed leaving the heterotopia and the visual tract fibers intact. Postoperatively preservation of the visual fields was documented and the frequency of seizures was markedly reduced.

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.