Refined Functional Magnetic Resonance Imaging and Magnetoencephalography Mapping Reveals Reorganization in Language-Relevant Areas of Lesioned Brains.

BACKGROUND: Neurosurgical decisions regarding interventions close to brain areas with language-related functions remain highly challenging because of the risk of postoperative dysfunction. To minimize these risks, improvements in the preoperative mapping of language-related regions are required, especially as space-occupying lesions often lead to altered cortical topography and language area reorganization. METHODS: The degree of deviation and language area reorganization were investigated in 26 functional magnetic resonance imaging- and magnetoencephalography-dissociable cortical sub-areas displaying language-related activations in each of 18 patients with brain lesions and 3 healthy volunteers (during visual language tasks). RESULTS: Both modalities showed good congruency of the language areas. The mean spatial distance of the centroids and maxima was 9.06 mm and 10.58 mm, respectively, allowing us to define more specific anatomical positions. Postoperatively, language abilities increased in 11% (2 of 18) of the patients, remained unchanged in 83% (15 of 18) of the patients, and decreased in 6% (1 of 18) of the patients, respectively. Signs of language function reorganization detected on both functional magnetic resonance imaging and magnetoencephalography were present in 29% (5 of 17) of the patients. Attenuation of neurovascular coupling was found postoperatively in 17% (3 of 18) of the patients. Monohemispheric language processing cannot be assumed always in patients with brain lesions. CONCLUSIONS: The more detailed subdivision of language-relevant brain areas shown in this study can help to achieve more radical tumor resection without postoperative language deficits.

Comparative fMRI and MEG localization of cortical sensorimotor function: Bimodal mapping supports motor area reorganization in glioma patients.

INTRODUCTION: Preoperative functional mapping in the vicinity of brain lesion is of high importance for avoiding complications in surgical management. However, space-occupying lesions may lead to functional reorganization or decreased BOLD activity. METHODS: Therefore in 13 patients with cerebral gliomas or brain arterio-venous malformations/ hemangioma fMRI- and MEG-based cortical localizations of motor and somatosensory cortical activation pattern were compared in order to investigate their congruency. RESULTS: Localization of cortical sensorimotor areas with fMRI and MEG showed good congruency with a mean spatial distance of around 10 mm, with differences depending on the localization method. The smallest mean differences for the centroids were found for MEF with MNE 8 mm and SEF with sLORETA 8 mm. Primary motor area (M1) reorganization was found in 5 of 12 patients in fMRI and confirmed with MEG data. In these 5 patients with M1-reorganization the distance between the border of the fMRI-based cortical M1-localization and the tumor border on T1w MR images varied between 0-4 mm, which was significant (P = 0.025) different to the distance in glioma patients without M1-reorganization (5-26 mm). CONCLUSION: Our multimodal preoperative mapping approach combining fMRI and MEG reveals a high degree of spatial congruence and provided high evidence for the presence of motor cortex reorganization.

Characterization of a Factual Knowledge-Associated Brain Memory Area by Functional Magnetic Resonance Imaging and Implementation in Tumor and Epilepsy Brain Surgery.

BACKGROUND: The role of the dominant hippocampus in verbal and episodic memory recall has been extensively investigated. However, there are categories of memory estimated independent of hippocampal function. In particular, factual knowledge is solely constituted from written or spoken input independent on undertaken experience, but the temporal structures involved are not well defined. METHODS: In this retrospective study, we mapped the activity of factual knowledge recall using functional magnetic resonance imaging (fMRI) in 60 patients scheduled for tumor or epilepsy surgery and in 18 patients resected within or close to the left mesial temporal lobe. Memory tests were performed preoperatively and postoperatively to investigate deficit symptoms in factual knowledge retrieval. RESULTS: We found a highly reproducible localized brain area within the parahippocampal gyrus, in the depth of the dorsal collateral sulcus, which was constantly involved in factual knowledge retrieval during fMRI tasks in 93% of patients (56/60) during recall of capital cities or multiplication tasks, in two thirds of the patients mainly on the dominant side. In addition, all 18 patients after surgery within this area showed postoperative factual knowledge deficits (56% permanent, 44% transitory), memory prognosis significantly correlating with the first day's factual knowledge retrieval task results. CONCLUSIONS: Using fMRI, we visualized a circumscribed brain area within the parahippocampal gyrus during factual knowledge retrieval, the lesioning of which led to factual knowledge deficits. Thus, impairment of factual knowledge retrieval may occur if resection is extended into the parahippocampal gyrus. Preoperative fMRI memory maps may contribute to avoiding such deficits.

Resective surgery for medically refractory epilepsy using intraoperative MRI and functional neuronavigation: the Erlangen experience of 415 patients.

OBJECTIVE: Intraoperative overestimation of resection volume in epilepsy surgery is a well-known problem that can lead to an unfavorable seizure outcome. Intraoperative MRI (iMRI) combined with neuronavigation may help surgeons avoid this pitfall and facilitate visualization and targeting of sometimes ill-defined heterogeneous lesions or epileptogenic zones and may increase the number of complete resections and improve seizure outcome. METHODS: To investigate this hypothesis, the authors conducted a retrospective clinical study of consecutive surgical procedures performed during a 10-year period for epilepsy in which they used neuronavigation combined with iMRI and functional imaging (functional MRI for speech and motor areas; diffusion tensor imaging for pyramidal, speech, and visual tracts; and magnetoencephalography and electrocorticography for spike detection). Altogether, there were 415 patients (192 female and 223 male, mean age 37.2 years; 41% left-sided lesions and 84.9% temporal epileptogenic zones). The mean preoperative duration of epilepsy was 17.5 years. The most common epilepsy-associated pathologies included hippocampal sclerosis (n = 146 [35.2%]), long-term epilepsy-associated tumor (LEAT) (n = 67 [16.1%]), cavernoma (n = 45 [10.8%]), focal cortical dysplasia (n = 31 [7.5%]), and epilepsy caused by scar tissue (n = 23 [5.5%]). RESULTS: In 11.8% (n = 49) of the surgeries, an intraoperative second-look surgery (SLS) after incomplete resection verified by iMRI had to be performed. Of those incomplete resections, LEATs were involved most often (40.8% of intraoperative SLSs, 29.9% of patients with LEAT). In addition, 37.5% (6 of 16) of patients in the diffuse glioma group and 12.9% of the patients with focal cortical dysplasia underwent an SLS. Moreover, iMRI provided additional advantages during implantation of grid, strip, and depth electrodes and enabled intraoperative correction of electrode position in 13.0% (3 of 23) of the cases. Altogether, an excellent seizure outcome (Engel Class I) was found in 72.7% of the patients during a mean follow-up of 36 months (range 3 months to 10.8 years). The greatest likelihood of an Engel Class I outcome was found in patients with cavernoma (83.7%), hippocampal sclerosis (78.8%), and LEAT (75.8%). Operative revisions that resulted from infection occurred in 0.3% of the patients, from hematomas in 1.6%, and from hydrocephalus in 0.8%. Severe visual field defects were found in 5.2% of the patients, aphasia in 5.7%, and hemiparesis in 2.7%, and the total mortality rate was 0%. CONCLUSIONS: Neuronavigation combined with iMRI was beneficial during surgical procedures for epilepsy and led to favorable seizure outcome with few specific complications. A significantly higher resection volume associated with a higher chance of favorable seizure outcome was found, especially in lesional epilepsy involving LEAT or diffuse glioma.

Risk reduction in dominant temporal lobe epilepsy surgery combining fMRI/DTI maps, neuronavigation and intraoperative 1.5-Tesla MRI.

BACKGROUND: In dominant temporal lobe epilepsy surgery, speech, memory and visual systems are at risk. OBJECTIVE: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging combined with intraoperative neuronavigation and MRI were investigated retrospectively regarding risk reductions for favorable neurological and seizure outcome. METHODS: Functional imaging risk maps were generated for 14 patients suffering from dominant temporal lobe epilepsy [7 with hippocampal sclerosis (HS), 7 with various lesions] and used for neuronavigation-guided tailored resection. Postoperative neurological and seizure outcome and complications were evaluated. RESULTS: None of the patients had postoperative speech dysfunction despite 2.3/3.6-cm mean hippocampal/neocortical resection. Verbal memory decline was found in 2 of the 14 (14.3%) patients, correlating with surgical lesions in fMRI memory-activated functional areas in the dominant posterior parahippocampal gyrus. Verbal memory scores did not statistically differ between the HS and the lesional group, neither pre- nor postoperatively. A contralateral visual field defect occurred in 1 patient (7.1%). An Engel class I seizure outcome was found in 12 patients (85.7%), and 11 were completely seizure free (78.6%) at a mean follow-up of 19.5 months. CONCLUSION: This retrospectively investigated protocol led to an excellent neurological and seizure outcome and a low complication rate in dominant temporal lobe epilepsy surgery.

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.

Frameless stereotactic functional neuronavigation combined with intraoperative magnetic resonance imaging as a strategy in highly eloquent located tumors causing epilepsy.

BACKGROUND: Intractable epilepsy due to tumors located in highly eloquent brain regions is often considered surgically inaccessible because of a high risk of postoperative neurological deterioration. Intraoperative MRI and functional navigation contribute to overcome this problem. OBJECTIVES: To retrospectively investigate the long-term results and impact of functional neuronavigation and 1.5-tesla intraoperative MRI on patients who underwent surgery of tumors associated with epilepsy located close to or within eloquent brain areas. METHODS: Nineteen patients (9 female, 10 male, mean age 41.4 ± 13.4 years, 11 low-grade and 8 high-grade glial tumors) were evaluated preoperatively using BOLD imaging, diffusion-tensor imaging tractography and magnetoencephalography. Functional data were implemented into neuronavigation in this multimodal approach. RESULTS: In 14 of 19 patients (74%), complete resection was achieved, and in 5 patients significant tumor volume reduction was accomplished. Eight of 14 (57%) complete resections were achieved only by performing an intraoperative image update. Neurological deterioration was found permanently in 2 patients. After a mean follow-up of 43.8 ± 23.8 months, 15 patients (79%) became seizure free (Engel class Ia). CONCLUSIONS: Despite the highly eloquent location of tumors causing intractable epilepsy, our multimodal approach led to complete resection in more than two-thirds of patients with an acceptable neurological morbidity and excellent long-term seizure control.

Integration of functional neuronavigation and intraoperative MRI in surgery for drug-resistant extratemporal epilepsy close to eloquent brain areas.

OBJECT: The authors performed a retrospective study to assess the impact of functional neuronavigation and intraoperative MRI (iMRI) on surgery of extratemporal epileptogenic lesions on postsurgical morbidity and seizure control. METHODS: Twenty-five patients (14 females and 11 males) underwent extratemporal resections for drug-resistant epilepsy close to speech/motor brain areas or adjacent to white matter tracts. The mean age at surgery was 34 years (range 12-67 years). The preoperative mean disease duration was 13.2 years. To avoid awake craniotomy, cortical motor-sensory representation was mapped during preoperative evaluation in 14 patients and speech representation was mapped in 15 patients using functional MRI. In addition, visualization of the pyramidal tract was performed in 11 patients, of the arcuate fascicle in 7 patients, and of the visual tract in 6 patients using diffusion tensor imaging. The mean minimum distance of tailored resection between the eloquent brain areas was 5.6 mm. During surgery, blood oxygen level-dependent imaging and diffusion tensor imaging data were integrated into neuronavigation and displayed through the operating microscope. The postoperative mean follow-up was 44.2 months. RESULTS: In 20% of these patients, further intraoperative resection was performed because of intraoperatively documented residual lesions according to iMRI findings. At the end of resection, the final iMRI scans confirmed achievement of total resection of the putative epileptogenic lesion in all patients. Postoperatively, transient complications and permanent complications were observed in 20% and 12% of patients, respectively. Favorable postoperative seizure control (Engel Classes I and II) was achieved in 84% and seizure freedom in 72% of these consecutive surgical patients. CONCLUSIONS: By using functional neuronavigation and iMRI for treatment of epileptogenic brain lesions, the authors achieved a maximum extent of resection despite the lesions' proximity to eloquent brain cortex and fiber tracts in all cases. The authors' results underline possible benefits of this technique leading to a favorable seizure outcome with acceptable neurological deficit rates in difficult-to-treat extratemporal epilepsy.

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.

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 cm(3) to 20.61 ± 21.67 cm(3) in first iMRI resection control, to finally 11.56 ± 21.92 cm(3) (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.

Classification of peritumoral fiber tract alterations in gliomas using metabolic and structural neuroimaging.

UNLABELLED: 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-(18)F-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-(18)F-fluoroethyl)-l-tyrosine uptake values were evaluated as ipsilateral-to-contralateral ratios. Four metabolic categories were defined on the basis of O-(2-(18)F-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.

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.

Observation of unaveraged giant MEG activity from language areas during speech tasks in patients harboring brain lesions very close to essential language areas: expression of brain plasticity in language processing networks?

We describe a series of 12 patients who suffered from lesions adjacent to the classic Broca and Wernicke areas and were examined by magnetoencephalography (MEG) for presurgical language localization while performing a protocol of different language tasks. In these patients very large MEG activity of up to 5pT was observed, which was located not only in the adjacent language processing brain areas but also in more distant areas, which are part of the language processing neuronal network. The high amplitude and the focal spatial extent of this activity allowed MEG source localization from the unaveraged data. In nine patients sources of this high amplitude activity were even found in the homologous language areas on the contralateral, the nondominant side of the brain. The physiological interrelationship of these large MEG changes needs to be investigated in more detail in further studies especially in the context of possible mechanisms for brain plasticity to overcome inhibitory activity of the impaired language area.