Andreas Merkel

A Frameless Stereotactic Implantation Technique for Depth Electrodes in Refractory Epilepsy Using Intraoperative Magnetic Resonance Imaging.

OBJECTIVE Various complex techniques for depth electrode insertion in refractory epilepsy using preoperative imaging have been investigated. We evaluated a simple, accurate, cost-effective, and timesaving method using intraoperative magnetic resonance imaging (MRI). METHODS A neuronavigation-guided insertion tube attached to bone facilitated the placement of stereotactic percutaneous drill holes, bolt implantation, and frameless stereotactic insertion of depth electrodes. Image registration was carried out by head coil fiducials with trajectory planning and intraoperative electrode correction. RESULTS In 6 patients with refractory epilepsy (3 women and 3 men; mean age, 30.0 years; range, 20-37 years), 58 depth electrodes (9-11 per patient) were placed. The mean length of the inserted electrodes was 37.3 mm ± 8.8 (mean ± SD) (range, 22.1-84.4 mm). The overall target point accuracy was 3.2 mm ± 2.2 (range, 0-8.6 mm), which was significantly different from the overall entry point accuracy of 1.4 mm ± 1.2 (P < 0.0001). All electrodes functioned perfectly, enabling high-quality stereo-electroencephalography recordings over a period of 7.3 days ± 0.5 (range, 7-8 days). The mean implantation time for 9-11 electrodes per patient was 115 minutes ± 36.3 (range, 75-160 minutes; 12 minutes for 1 electrode on average) including the intraoperative MRI (T1 three-dimensional magnetization-prepared rapid acquisition gradient echo, T2, and diffusion tensor imaging). There was no hemorrhage, infection, or neurologic deficit related to the procedure. CONCLUSIONS Our frameless technique of depth electrode insertion using intraoperative MRI guidance is an accurate, reliable, cost-effective, and timesaving method for stereo-electroencephalography.

Supra-complete surgery via dual intraoperative visualization approach (DiVA) prolongs patient survival in glioblastoma

Safe and complete resection represents the first step in the treatment of glioblastomas and is mandatory in increasing the effectiveness of adjuvant therapy to prolong overall survival. With gross total resection currently limited in extent to MRI contrast enhancing areas, the extent to which supra-complete resection beyond obvious contrast enhancement could have impact on overall survival remains unclear. DiVA (dual intraoperative visualization approach) redefines gross total resection as currently accepted by enabling for the first time supra-complete surgery without compromising patient safety. This approach exploits the advantages of two already accepted surgical techniques combining intraoperative MRI with integrated functional neuronavigation and 5-ALA by integrating them into a single surgical approach. We investigated whether this technique has impact on overall outcome in GBM patients. 105 patients with GBM were included. We achieved complete resection with intraoperative MRI alone according to current best-practice in glioma surgery in 75 patients. 30 patients received surgery with supra-complete resection. The control arm showed a median life expectancy of 14 months, reflecting current standards-of-care and outcome. In contrast, patients receiving supra-complete surgery displayed significant increase in median survival time to 18.5 months with overall survival time correlating directly with extent of supra-complete resection. This extension of overall survival did not come at the cost of neurological deterioration. We show for the first time that supra-complete glioma surgery leads to significant prolongation of overall survival time in GBM patients.

Intraoperative vascular DIVA surgery reveals angiogenic hotspots in tumor zones of malignant gliomas

Malignant gliomas belong to the most threatening tumor entities and are hallmarked by rapid proliferation, hypervascularization and an invasive growth pattern. The primary obstacle in surgical treatment lies in differentiation between healthy and pathological tissue at the tumor margins, where current visualization methods reach their limits. Here, we report on a novel technique (vascular dual intraoperative visualization approach - vDIVA) enabling visualization of different tumor zones (TZ I–III) on the basis of angiogenic hotspots. We investigated glioblastoma patients who underwent 5-ALA fluorescence-guided surgery with simultaneous intraoperative ICG fluorescence angiography. This vDIVA technique revealed hypervascularized areas which were further histologically investigated. Neuropathological assessments revealed tissue areas at the resection margins corresponding to TZ II, and postoperative CD34- and Map2 immunostaining confirmed these angiogenic hotspots to be occupied by glioma cells. Hence, the vascular architecture in this transitional zone could be well differentiated from both primary tumor bulk and healthy brain parenchyma. These data demonstrate that ICG fluorescence angiography improves state-of-the-art glioma surgery techniques and facilitates the future characterization of polyclonal attributes of malignant gliomas.

A new functional classification system (FGA/B) with prognostic value for glioma patients

Despite advances in multimodal treatments, malignant gliomas remain characterized by a short survival time. Surgical treatment is accepted to be the first line of therapy, with recent studies revealing that maximal possible tumor reduction exerts significant impact on patient outcome. Consideration of tumor localization in relation to functionally eloquent brain areas has been gaining increasing importance. Despite existing assessment methods, the availability of a simple but reliable preoperative grading based on functional data would therefore prove to be indispensable for the prediction of postoperative outcome and hence for overall survival in glioma patients. We performed a clinical investigation comprising 322 patients with gliomas and developed a novel classification system of preoperative tumor status, which considers tumor operability based on two graduations (Friedlein Grading - FG): FGA with lesions at safe distance to eloquent regions which can be completely resected, and FGB referring to tumors which can only be partially resected or biopsied. Investigation of outcome revealed that FGA were characterized by a significantly longer overall survival time compared to FGB. We offer the opportunity to classify brain tumors in a dependable and reproducible manner. The FGA/B grading method provides high prognostic value with respect to overall survival time in relation to the extent of location-dependent tumor resection.

Intraoperative MRT (iopMRT) in der Gliomchirurgie

Die intraoperative MRT-Bildgebung in der Gliomchirurgie ist auch mehr als 20 Jahre nach ihrer erstmaligen Einfuhrung eine ganz wesentliche Hilfe zur Verbesserung des Resektionsausmases. Die moglichst vollstandige Resektion von Gliomen bildete nach wie vor den ersten und entscheiden Schritt in der Therapie, trotz aller Fortschritte in Radioonkologie, medikamentoser und Immuntherapie. Die Radikalitat der Resektion soll jedoch nicht zulasten der neurologischen Funktion des Patienten gehen. Ein Zurucklassen prinzipiell resektabler Tumoranteile verschlechtert nach heutiger Auffassung das Langzeitergebnis des Eingriffs. Die MRT-Bildgebung wurde daher als logischer Schritt Anfang der 1990er Jahre in das operative Verfahren integriert. Seitdem wurde sie bestandig weiter entwickelt. Die Verbesserung des Resektionausmases ist durch zahlreiche Studien fur Niederfeld- wie fur Hochfeldsysteme belegt, in letzter Zeit fur 3-Tesla-Systeme. Das Kapitel zeigt den Stellenwert der intraoperativen Bildgebung in der Gliomchirurgie auf, geht aber auch auf Probleme ein und teilt mit potenziellen Anwendern praktische Erfahrung, die uber ein Jahrzehnt gesammelt wurde.