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Glioblastoma (GBM) is the most common primary intracranial neoplasia, and is characterized by its extremely poor prognosis. Despite maximum surgery, chemotherapy, and radiation, the histological heterogeneity of GBM makes total eradication impossible, due to residual cancer cells invading the parenchyma, which is not otherwise seen in radiographic images. Even with gross total resection, the heterogeneity and the dormant nature of brain tumor initiating cells allow for therapeutic evasion, contributing to its recurrence and malignant progression, and severely impacting survival. Visual delimitation of the tumor's margins with common surgical techniques is a challenge faced by many surgeons. In an attempt to achieve optimal safe resection, advances in approaches allowing intraoperative analysis of cancer and non-cancer tissue have been developed and applied in humans resulting in improved outcomes. In addition, functional paradigms based on stimulation techniques to map the brain's electrical activity have optimized glioma resection in eloquent areas such as the Broca's, Wernike's and perirolandic areas. In this review, we will elaborate on the current standard therapy for newly diagnosed and recurrent glioblastoma with a focus on surgical approaches. We will describe current technologies used for glioma resection, such as awake craniotomy, fluorescence guided surgery, laser interstitial thermal therapy and intraoperative mass spectrometry. Additionally, we will describe a newly developed tool that has shown promising results in preclinical experiments for brain cancer: optical coherence tomography., Competing Interests: The authors declare no conflict of interest.

Object: Navigated transcranial magnetic stimulation (nTMS) combined with diffusion tensor imaging (DTI) is used preoperatively in patients with eloquent-located brain lesions and allows analyzing non-invasively the spatial relationship between the tumor and functional areas (e.g. the motor cortex and the corticospinal tract [CST]). In this study, we examined the diffusion parameters FA (fractional anisotropy) and ADC (apparent diffusion coefficient) within the CST in different locations and analyzed their interrater reliability and usefulness for predicting the patients' motor outcome with a precise approach of specific region of interest (ROI) seeding based on the color-coded FA-map., Methods: Prospectively collected data of 30 patients undergoing bihemispheric nTMS mapping followed by nTMS-based DTI fiber tracking prior to surgery of motor eloquent high-grade gliomas were analyzed by 2 experienced and 1 unexperienced examiner. The following data were scrutinized for both hemispheres after tractography based on nTMS-motor positive cortical seeds and a 2nd region of interest in one layer of the caudal pons defined by the color-coded FA-map: the pre- and postoperative motor status (day of discharge und 3 months), the closest distance between the tracts and the tumor (TTD), the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC). The latter as an average within the CST as well as specific values in different locations (peritumoral, mesencephal, pontine)., Results: Lower average FA-values within the affected CST as well as higher average ADC-values are significantly associated with deteriorated postoperative motor function (p = 0.006 and p = 0.026 respectively). Segmental analysis within the CST revealed that the diffusion parameters are especially disturbed on a peritumoral level and that the degree of their impairment correlates with motor deficits (FA p = 0.065, ADC p = 0.007). No significant segmental variation was seen in the healthy hemisphere. The interrater reliability showed perfect agreement for almost all analyzed parameters., Conclusions: Adding diffusion weighted imaging derived information on the structural integrity of the nTMS-based tractography results improves the predictive power for postoperative motor outcome. Utilizing a second subcortical ROI which is specifically seeded based on the color-coded FA map increases the tracking quality of the CST independently of the examiner's experience. Further prospective studies are needed to validate the nTMS-based prediction of the patient's outcome.

OBJECTIVE Navigated transcranial magnetic stimulation (nTMS) is a noninvasive method for preoperatively localizing functional areas in patients with tumors in presumed motor eloquent areas. The aim of this study was to establish an nTMS-based risk stratification model by examining whether the results of nTMS mapping and its neurophysiological data predict postoperative motor outcome in glioma surgery. METHODS Included in this study were prospectively collected data for 113 patients undergoing bihemispheric nTMS examination prior to surgery for gliomas in presumed motor eloquent locations. Multiple ordinal logistic regression analysis was performed to test for any association between preoperative nTMS-related variables and postoperative motor outcome. RESULTS A new motor deficit or deterioration due to a preexisting deficit was observed in 20% of cases after 7 days and in 22% after 3 months. In terms of tumor location, no new permanent deficit was observed when the distance between tumor and corticospinal tract was greater than 8 mm and the precentral gyrus was not infiltrated (p = 0.014). New postoperative deficits on Day 7 were associated with a pathological excitability of the motor cortices (interhemispheric resting motor threshold [RMT] ratio < 90% or > 110%, p = 0.031). Interestingly, motor function never improved when the RMT was significantly higher in the tumorous hemisphere than in the healthy hemisphere (RMT ratio > 110%). CONCLUSIONS The proposed risk stratification model, based on objective functional-anatomical and neurophysiological measures, enables one to counsel patients about the risk of functional deterioration or the potential for recovery.

Neurocognitive assessment becomes increasingly important in neuro-oncology. The presence and degree of neurocognitive deficits in patients with brain tumors appear to be important not only as outcome measures but also in treatment planning and as possible prognostic markers for tumor-progression. Common screening methods for neurocognitive deficits are often insufficient in uncovering subtle changes or harbor the risk of being observer-dependent and time-consuming. We present data of brain tumor patients screened by a computer-based neurocognitive assessment tool before and after surgery. 196 patients with tumor resections were tested at our institution using the NeuroCog Fx® software 2days before and 3-4months after surgery. Additionally to the test results, patient-related information, such as age, sex, handedness, level of education, pre- and postoperative neurological status, KPS, location and histopathological diagnosis were recorded. These prospectively collected results were correlated in the here presented retrospective study. The majority of patients with malignant gliomas, metastases and meningiomas showed significant deficits in various neurocognitive domains, most of them improved or did not decline in their postoperative neurocognitive performances. Interestingly, there was no significant correlation of neurocognitive deficits and brain tumor location. In future, standardized neuropsychological assessment should become an essential part of the management and care of patients with brain tumors to provide a more personalized and tailored treatment. Further studies will improve the understanding of the influence of various treatment modalities on neuro-cognition., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: In recent years laser interstitial thermal therapy (LITT) has become the ablative neurosurgical procedure of choice. Multiple methods for registration and laser fiber verification have been described, with each method requiring multiple steps and significant time expenditure. We evaluated the use of a commercially available mobile computed tomography (CT) scanner for stereotactic registration during LITT for brain tumors in an attempt to simplify the procedure and improve intraoperative awareness of laser position., Methods: This is a retrospective chart review comparing LITT of brain tumors in 23 patients undergoing a standard protocol requiring skull pins and transport of the patient to a CT suite to obtain a reference scan compared with 14 patients in whom the Medtronic O-arm was used intraoperatively for navigation registration and confirmation of laser position., Results: Total ablation of the target was achieved in all patients with no surgical complications. Total surgery time was shorter for the O-arm group than for the standard protocol group, once experience was gained with bringing the O-arm in and out of the surgical field. Return from the magnetic resonance imaging suite to the operating room for repositioning of the laser was required for 1 patient in the standard protocol group, but for no patients in the O-arm group. Once experience was gained with using the O-arm, estimated surgical costs were lower for this group., Conclusions: Use of a mobile intraoperative CT scanner for navigation registration and confirmation of laser position during LITT may play a role in streamlining the procedure and improving patient safety and comfort., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Some tumor-specific near-infrared (NIR) fluorescent dyes such as indocyanine green (ICG), IDRye800CW, and 5-aminolevulinic acid have been used clinically for detecting tumor margins or micro-cancer lesions. In this study, we evaluated the physicochemical properties of liposomally formulated phospholipid-conjugated ICG, denoted by LP-iDOPE, as a clinically translatable NIR imaging nanoparticle for brain tumors. We also confirmed its brain-tumor-specific biodistribution and its characteristics as the intra-operative NIR imaging nanoparticles for brain tumor surgery. These properties of LP-iDOPE may enable neurosurgeons to achieve more accurate identification and more complete resection of brain tumor., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Awake craniotomy (AC) in brain lesions has allowed an improvement of both oncologic and functional results. However, intraoperative seizures (IOSs) were reported as a cause of failure of AC. Here, we analyze the incidence, risk factors, and consequences of IOSs in a prospective cohort of 374 ACs without electrocorticography (ECoG)., Methods: We performed a prospective study including all patients who underwent AC for an intra-axial supratentorial cerebral lesion from 2009-2014 in our department. Occurrence of IOS was analyzed with respect to medical and epilepsy history, tumor characteristics, operative technique, and postoperative outcomes., Results: The study comprised 374 patients with a major incidence of low-grade glioma (86%). Most of the patients (83%) had epilepsy history before surgery (20% had intractable seizures). Preoperative mean Karnofsky performance scale (KPS) score was 91. IOSs occurred in 13 patients (3.4%). All IOSs were partial seizures, which quickly resolved by irrigation with cold Ringer lactate. No procedure failed because of IOS, and the rate of aborted AC whatever the cause was nil. Mean stimulation current intensity for cortical and subcortical mapping was 2.25 ± 0.6 mA. Presurgical refractory epilepsy was not associated with a higher incidence of IOS. Three months after surgery, no patients had severe or disabling permanent worsening, even within the IOS group (mean KPS score of 93.7)., Conclusions: AC for intra-axial brain lesion can be safely and reproducibly achieved without ECoG, with a low rate of IOS and excellent functional results, even in patients with preoperative intractable epilepsy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Histopathological examination is the standard for grading and determination of diagnosis in intrinsic brain tumors though the possibility of malignization and tumor heterogeneity always bears the possibility of tumor under-grading or misjudgement regarding the estimation of prognosis. The aim of the present study was to evaluate the use of (18)F-FET-PET (FET-PET) for the grading and estimation of prognosis in newly diagnosed patients with intracranial gliomas in a clinical setting., Methods: Patients who were treated for a newly diagnosed intracranial glioma between January 2007 and May 2012, and had a preoperative FET-PET and MRI scan between were included. The ratio of counts in a tumor VOI (volume of interest) with maximum uptake to the respective counts in a background VOI was calculated to provide the tumor-to-normal (T/N) ratio. The clinical and histopathological data (tumor grading, pre- and postoperative neurological status, Karnofsky Performance Status Scale scores, and overall survival rates) were recorded., Results: One hundred fifty-two patients (39 WHO II, 26 WHO III, 87 WHO IV) were included. The median T/N ratio was 2.81 (1.1-8.1). The median T/N ratio of low-grade glioma patients was 1.65 (1.1-3.7), and 3.14 (1.61-8.1, p<0.001) in high-grade glioma patients. The median survival for patients with WHO III tumors was 22.8 months (95% CI: 15.87%-NA) and 13.23 months (95% CI: 10.83-15.6.%) for patients with WHO IV tumors (p=0.0001). For T/N≤1.6, no deaths were recorded; for 1.63, median survival was 14.0 months (95% CI: 11.7-16.2%, p<0.001). The test of the maximally selected log-rank statistic resulted in a T/N ratio of 1.88 as the cut-off value, with the greatest difference in overall survival between patients with longer and shorter survival. The ROC curve for differentiation of low- vs. high-grade tumors with regard to the T/N ratio showed an area under the curve (AUC) of 0.903. Regarding the prognostic validity for overall survival ROC-curves for 12-month, 24-month and 48-month survival display a higher validity for the WHO-classification than for the imaging modalities though with an AUC of 0.847 for the 48-month survival T/N ratio and MRI contrast-enhancement have a high prognostic value as well., Conclusion: Our study suggests that FET-PET can predict prognosis and survival in patients harboring intracranial gliomas and serves as a valuable tool to supplement the established clinical and histopathological parameters., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Functional magnetic resonance imaging (fMRI) for motor and language mapping is used for presurgical planning. This study aimed to evaluate the value of fMRI in clinical routine for preoperative planning of brain surgery adjacent to functional brain areas., Methods: Thirty-seven consecutive patients with brain lesions adjacent to sensomotor and/or language functional areas underwent fMRI prior to planned brain surgery on a 3T MRI scanner for identification of motor in all and language functional areas in 29 patients. Analysis software installed on the MRI console was used for rapid image analysis and direct visualization. All fMRI results were analyzed according to the use for preoperative planning., Results: fMRI data analysis and visualization was possible in less than 10min. In 35 patients fMRI of motor cortex and in 25 patients fMRI of language could be performed due to the patient's compliance. In 34 patients motor activity could be clearly identified in the precentral gyrus. The dominant hemisphere could be identified clearly in 22 cases. In 18 patients direct anatomical correlation of the activity maps to the speech area of Broca and/or Wernicke could be made. Resection surgery was performed in all patients. 11 patients underwent awake surgery with intraoperative cortical stimulation., Conclusion: fMRI for clinical routine is a reliable and rapid method for identification of functional brain areas prior to brain surgery adjacent to functional areas. This method allows direct monitoring of the data quality and visualization without being time consuming. Knowledge about the relation of functional areas to the brain lesions improves the preoperative planning, the operation strategy and decision making with patients., (Copyright © 2014. Published by Elsevier B.V.)

Objectives: To study the propensity of different cancers to metastasize to the cerebrum and cerebellum, and to study overall survival (OS) and prognostic factors for patients after surgical resection for cerebellar metastases., Materials and Methods: From a prospectively collected tumor database, all patients that underwent a craniotomy for intracranial metastases between 2003 and 2011 at Oslo University Hospital were included., Results: One hundred and forty patients underwent resection for cerebellar metastases. Most common primary tumor sites were lung, colon/rectum, and breast in 45%, 19%, and 14%, respectively. None were prostate cancers. Melanoma metastases were significantly underrepresented, and colorectal cancer metastases significantly overrepresented in cerebellum, compared to the overall proportion of cerebellar/supratentorial metastases surgically resected (P < 0.05). Thirty-day post-operative mortality rate was 4.3%. Median OS was 7.7 months (95% CI 6.0-9.5 months) irrespective of post-operative adjuvant therapy. Median OS was 51.8, 8.4, and 3.4 months, respectively, for recursive partitioning analysis class 1(n = 11), 2 (n = 78) and 3 (n = 34). Significant negative prognostic factors were age ≥65 years, Karnofsky performance score (KPS) <70, extracranial metastases and uncontrolled systemic disease., Conclusions: Melanoma metastases were significantly underrepresented in cerebellum, whereas colorectal cancer metastases were significantly overrepresented. Surgical mortality and OS after surgical treatment of cerebellar metastases were similar to the results of supratentorial metastases., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background Leksell GammaPlan (LGP) and SurgiPlan (ELEKTA Instruments AB, Stockholm, Sweden) may be used effectively for the detailed evaluation of regional neuroanatomy before open neurosurgical procedures. We report our initial experience in the cases of cerebral gliomas. Methods LGP v.8.3 was used before the surgical resection of cerebral gliomas for (1) the delineation of subdural grid electrodes and a detailed evaluation of their position relatively to cortical structures, and (2) for the fusion of structural magnetic resonance imaging and diffusion tensor imaging (DTI) for a detailed visualization of the corticospinal tract (CST) and optic radiation. Results Delineation of the subdural grid within LGP in a patient with seizures caused by left parietal glioma permitted a detailed assessment of the location of electrodes relative to the cortical gyri and sulci and significantly facilitated interpretation of brain mapping before tumor resection. In another patient with parieto-occipital glioma, simultaneous three-dimensional visualization of the tumor, CST, and optic radiation with the use of LGP permitted us to perform tumor resection without postoperative neurologic complications. Finally, incorporation of DTI into SurgiPlan resulted in precise planning of stereotactic biopsy for bilateral thalamic glioma. Conclusion The possibility for detailed evaluation of regional neuroanatomy based on various images within LGP and SurgiPlan may facilitate effective and safe surgical management of intracranial gliomas.