Peter Grummich

Magnetic source imaging supports clinical decision making in glioma patients

OBJECTIVE This study addresses the potential utility of preoperative functional imaging with magnetoencephalography (MEG) for the selection of glioma patients who are likely to benefit from resective surgical treatment regarding postoperative morbidity. METHODS One hundred and nineteen patients with gliomas adjacent to sensorimotor, visual and speech related brain areas were investigated preoperatively with a MAGNES II biomagnetometer. In each patient the pre-surgical evaluation was focussed on the visual, sensorimotor cortex and/or of the speech related brain areas. A grading system was then used according to the distance of the MEG activation sources to the nearest tumour border to determine the further treatment. The therapeutic options consisted in conservative treatment, stereotactic biopsy and/or a radiation and chemotherapy, substantial cytoreduction and the gross total removal of the lesion. RESULTS From 119 investigated patients, 55 patients (46.2%) were not considered for surgery due to tumour invasion to functional cortex. Sixty four patients (53.8%) were chosen for resective surgery. In the surgical group only four patients (6.2%) suffered from neurological deterioration. CONCLUSIONS Magnetic source imaging (MSI) proved to be a valuable help in the clinical decision making process of lesions adjacent to functional important brain areas. The relative high number of patients in whom MSI warns of the postoperative crippling sequelae may lead to a better selection of patients who benefit from resective surgery. This method may help to find the patients for whom conservative treatment seems to be more favourable concerning quality of life in the surviving time.

Combining fMRI and MEG increases the reliability of presurgical language localization: a clinical study on the difference between and congruence of both modalities.

To avoid neurological impairment during surgery near language-related eloquent brain areas, we performed presurgical functional brain mapping with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in 172 patients using language tasks. For MEG localizations, we used either a moving equivalent-current dipole fit or a current-density reconstruction using a minimum variance beamformer with a spatial filter algorithm. We localized the Wernicke and Broca language areas for every patient. We integrated the results into a frameless stereotaxy system. To visualize the results in the navigation microscope during surgery, we superimposed the fMRI and MEG findings on the brain surface. MEG and fMRI results differed in 4% of cases, and in 19%, one modality showed activation but not the other. In the vicinity of large gliomas, the BOLD (blood oxygenation level-dependent) effect was suppressed in 53% of our patients. Of the 124 patients who had surgery, only 7 patients (5.6%) experienced a transient language deterioration, which resolved in all cases. We used MEG and fMRI to show different aspects of brain activity and to establish validation between MEG and fMRI. We conclude that measurement by both MEG and fMRI increases the degree of reliability of language area localization and that the combination of fMRI and MEG is useful for presurgical localization of language-related eloquent cortex.

Improving the extent of malignant glioma resection by dual intraoperative visualization approach.

Despite continuing debates around cytoreductive surgery in malignant gliomas, there is broad consensus that increased extent of tumor reduction improves overall survival. However, maximization of the extent of tumor resection is hampered by difficulty in intraoperative discrimination between normal and pathological tissue. In this context, two established methods for tumor visualization, fluorescence guided surgery with 5-ALA and intraoperative MRI (iMRI) with integrated functional neuronavigation were investigated as a dual intraoperative visualization (DIV) approach. Thirty seven patients presumably suffering from malignant gliomas (WHO grade III or IV) according to radiological appearance were included. Twenty-one experimental sequences showing complete resection according to the 5-ALA technique were confirmed by iMRI. Fourteen sequences showing complete resection according to the 5-ALA technique could not be confirmed by iMRI, which detected residual tumor. Further analysis revealed that these sequences could be classified as functional grade II tumors (adjacent to eloquent brain areas). The combination of fluorescence guided resection and intraoperative evaluation by high field MRI significantly increased the extent of tumor resection in this subgroup of malignant gliomas located adjacent to eloquent areas from 61.7% to 100%; 5-ALA alone proved to be insufficient in attaining gross total resection without the danger of incurring postoperative neurological deterioration. Furthermore, in the case of functional grade III gliomas, iMRI in combination with functional neuronavigation was significantly superior to the 5-ALA resection technique. The extent of resection could be increased from 57.1% to 71.2% without incurring postoperative neurological deficits.

Sources of spontaneous slow waves associated with brain lesions, localized by using the MEG.

SummaryElectric or magnetic slow wave brain activity can be associated with brain lesions. For an accurate source localization we transformed the magnetoencephalographic (MEG) coordinate system to the magnetic resonance imaging (MRI) system by using a surface fit of the digitally measured head surface and the reconstructed surface of the MRI scan. Furthermore we solved the problem to separate sources of focal activity from other multiple sources by introducing a spatial average, the Dipole Density Plot (DDP). The DDP shows in a quantified manner concentrations of dipoles across time. The DDP uses the single dipole model adequately, because only those signal sections will be analyzed, where one component contributes to the signal predominantly. In all cases, where multiple sources concurrently active are to be localized, a current distribution analysis will be used, the Current Localization by Spatial Filtering (CLSF). All source localization procedures were tested using structural brain lesions, which were verified by imaging techniques (MRI or CT), showing the results in close topographical relation to the lesions. The results so far let us assume, that the DDP and the CLSF are valuable tools to localize sources of focal spontaneous slow wave electrical brain activity.

Intraoperative Visualization of Fiber Tracking Based Reconstruction of Language Pathways in Glioma Surgery

BACKGROUND: For neuroepithelial tumors, the surgical goal is maximum resection with preservation of neurological function. This is contributed to by intraoperative magnetic resonance imaging (iMRI) combined with multimodal navigation. OBJECTIVE: We evaluated the contribution of diffusion tensor imaging (DTI)-based fiber tracking of language pathways with 2 different algorithms (tensor deflection, connectivity analysis [CA]) integrated in the navigation on the surgical outcome. METHODS: We evaluated 32 patients with neuroepithelial tumors who underwent surgery with DTI-based fiber tracking of language pathways integrated in neuronavigation. The tensor deflection algorithm was routinely used and its results intraoperatively displayed in all cases. The CA algorithm was furthermore evaluated in 23 cases. Volumetric assessment was performed in pre- and intraoperative MR images. To evaluate the benefit of fiber tractography, language deficits were evaluated pre- and postoperatively and compared with the volumetric analysis. RESULTS: Final gross-total resection was performed in 40.6% of patients. Absolute tumor volume was reduced from 55.33 ± 63.77 cm3 to 20.61 ± 21.67 cm3 in first iMRI resection control, to finally 11.56 ± 21.92 cm3 (P < .01). Fiber tracking of the 2 algorithms showed a deviation of the displayed 3D objects by <5 mm. In long-term follow-up only 1 patient (3.1%) had a persistent language deficit. CONCLUSION: Intraoperative visualization of language-related cortical areas and the connecting pathways with DTI-based fiber tracking can be successfully performed and integrated in the navigation system. In a setting of intraoperative high-field MRI this contributes to maximum tumor resection with low postoperative morbidity.

Improved resection in lesional temporal lobe epilepsy surgery using neuronavigation and intraoperative MR imaging: Favourable long term surgical and seizure outcome in 88 consecutive cases

PURPOSE To investigate the value of intraoperative MR imaging (iopMRI) combined with neuronavigation to avoid intraoperative underestimation of the resection amount during surgery of lesional temporal lobe epilepsy (LTLE) patients. METHODS We retrospectively investigated 88 patients (40 female, 48 male, mean age 37.2 yrs, from 12 to 69 yrs, 41 left sided lesions) with LTLE operated at our department, including 40.9% gangliogliomas (GG), 26.1% cavernomas (CM), 10.2% dysembryoplastic neuroepithelial tumours (DNT) and 11.4% focal cortical dysplasias (FCD), excluding hippocampal sclerosis. RESULTS Complete resection was achieved in 85 of 88 patients (96.6%), as proven by postoperative MRI 6 months after surgery. In contrast, the routine first iopMR imaging before closure revealed radical resection in only 66 of these 88 patients (75%). After re-intervention, the second iopMR imaging demonstrated complete resection in 19 more patients. Thus, as a direct effect of iopMRI and neuronavigation, overall resection rate was increased by 21.6%. An excellent seizure outcome Engel Class I was found in 76.1% of patients during a mean follow-up of 26.4 months, irrespective of histological entity (74% in CM, 75% in GG, 78% in DNT and 60% in FCD). No severe postoperative complications occurred; permanent superior visual field defects were detected in 10.2% and permanent dysphasia/dyscalculia in 1.1%. CONCLUSION Refined surgery using neuronavigation combined with iopMR imaging in LTLE surgery led to radical resection in 96.6% of the patients, due to immediate correction of underestimated resection in 21.6% of patients. This protocol resulted in a favourable seizure outcome and a low complication rate.

THE FACTOR ANALYSIS USED TO IMPROVE THE DIPOLE-DENSITY-PLOT (DDP) TO LOCALIZE FOCAL CONCENTRATIONS OF SPONTANEOUS MAGNETIC BRAIN ACTIVITY

INTRODUCTION In previous studies we showed that concentrations of spontaneous, slow wave, focal, magnetic brain activity can be quantificd, localized and markcd in the corresponding MRI slices using thc dipoledensityplot (DDP) (2,3,5,6). We necded this because we found the sources of such activity not only concentrated in the vicinity of structural and verified brain lesions but also in some distance (1,2,4). The concentration effect will bc rcachcd by the following measures: (1) selection of only thosc dipoles which will fit predominantly the single dipole model to omit multifocal or distributed activity, (2) summation of dipole estimations across time to get a spatial avcrage with the chance to increase thc focal concentrations for lower dipole densities by increasing the analyzing time.

Estimates of brain activity using Magnetic Field Tomography in a GO/NOGO avoidance paradigm

SummaryThis paper presents the first estimates of three dimensional evolution of activity in the brain associated with a GO/NOGO avoidance (CNV) paradigm. These estimates are continuous probabilistic solutions (Ioannides et al. 1990) to the biomagnetic inverse problem, obtained from averaged multichannel magnetoencephalographic (MEG) recordings (Vieth et al. 1991). The emphasis here is placed on the comparison of the activity associated with the GO and NOGO conditions; estimates of activity are shown for the onset of warning stimulus (S1), the early response half a second after S1, the late response lasting for over one second before S2 (the time between S1 and S2 is 3.5 seconds) and the onset of the imperative stimulus (S2). We find responses in regions of the brain implicated with hearing the stimulus, task engagement and motor output. Differences in the images corresponding to GO and NOGO conditions are significant because they reflect differences in brain function when a motor response is required or must be inhibited.

Three dimensional localization of the pathological area in cerebro-vascular accidents with multichannel magnetoencephalography.

In these .single channel studies we found a sufficient validation of the locahzation of pathological activity, since in 24 patients with venfied bram lesions the estimated single dipoles were located in the vicinity of the lesions (4,5,6,7,8). But using a single channel instruxncni the spatiotemporal dynamics of the bram activity was lost, and the resulting dipoles were onJy show ing the point of gravity of the activity during the time analyzed.

Classification of Peritumoral Fiber Tract Alterations in Gliomas Using Metabolic and Structural Neuroimaging

The aims of this study were to investigate and categorize peritumoral fiber tract alterations while considering changes in metabolism and integrity of fiber structures using multimodal neuroimaging—that is, PET with O-(2-18F-fluoroethyl)-l-tyrosine and diffusion tensor imaging evaluated by fiber density mapping—and to correlate categories of fiber alterations with preoperative neurologic deficits and postoperative course. Methods: We examined 26 patients with cerebral gliomas. Fiber density data were used to segment peritumoral fiber structures and were coregistered to anatomic MR images and PET data. Fiber density and O-(2-18F-fluoroethyl)-l-tyrosine uptake values were evaluated as ipsilateral-to-contralateral ratios. Four metabolic categories were defined on the basis of O-(2-18F-fluoroethyl)-l-tyrosine values: tumor-infiltrated tissue, reactive tissue (astrogliosis and microglial activation), normal brain tissue, and tissue with attenuated amino acid metabolism. Fiber density values were grouped in 3 categories for structural integrity: compressed, normal, and attenuated fibers. Results: We evaluated and classified 103 peritumoral fiber structures with 10 patterns of fiber tract alterations. Fiber structures in tumor-infiltrated, reactive, and normal brain tissue showed compressed fibers, displaced fibers, and (partly) destroyed fibers, respectively. Attenuated amino acid metabolism was associated only with attenuated fiber density. Thirteen patients showed white matter–related neurologic deficits (paresis, hypoesthesia, aphasia, or anopia) as initial symptoms. Three patients showed tumor infiltration in the corresponding fiber tracts; all the others had reactive or normal brain tissue. Fiber structures were compressed or attenuated but not normal. The 3 patients with tumor infiltration in the corresponding fiber tracts and 1 with compressed fibers in normal brain showed no improvements or worsening of the deficits in the postoperative course. Eight patients with the corresponding fiber tracts in reactive or normal brain areas showed improvement of deficits. One patient underwent biopsy only. Conclusion: Our multimodal neuroimaging approach provides complementary information and more detailed understanding of peritumoral fiber tract alterations in gliomas which are more complex as described so far. We presented a classification model for systematic assessment of these alterations that may be helpful for treatment planning and prediction of patients’ prognoses.