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The physiologic processes underlying MRI contrast enhancement in glioblastoma patients remain poorly understood. MRIs of 148 glioblastoma subjects from The Cancer Imaging Archive were segmented using Iterative Probabilistic Voxel Labeling (IPVL). Three aspects of contrast enhancement (CE) were parametrized: the mean intensity of all CE voxels (CE i ), the intensity heterogeneity in CE (CE h ), and volumetric ratio of CE to necrosis (CE r ). Associations between these parameters and patterns of gene expression were analyzed using DAVID functional enrichment analysis. Glioma CpG island methylator phenotype (G-CIMP) glioblastomas were poorly enhancing. Otherwise, no differences in CE parameters were found between proneural, neural, mesenchymal, and classical glioblastomas. High CE i was associated with expression of genes that mediate inflammatory responses. High CE h was associated with increased expression of genes that regulate remodeling of extracellular matrix (ECM) and endothelial permeability. High CE r was associated with increased expression of genes that mediate cellular response to stressful metabolic states, including hypoxia and starvation. Our results indicate that CE in glioblastoma is associated with distinct biological processes involved in inflammatory response and tissue hypoxia. Integrative analysis of these CE parameters may yield meaningful information pertaining to the biologic state of glioblastomas and guide future therapeutic paradigms., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Magnetic resonance imaging (MRI)-guided biopsy is an emerging diagnostic technique that holds great promise for otherwise difficult to access neuroanatomy., Case Description: Here we describe MRI-guided biopsy of a suprasellar lesion located posterior and superior to the pituitary stalk. The approach was implemented successfully in a 38-year-old woman who had developed progressive visual deterioration., Conclusion: Intraoperative MRI revealed the need for trajectory adjustment due to an unintended, minor deviation in the burr hole entry point, demonstrating the benefit of an MRI-guided approach. Langerhans cell histiocytosis was diagnosed after biopsy, and the lesion regressed after cladribine treatment. Technical nuances of the case are reviewed in the context of the available literature., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Mass effect has demonstrated prognostic significance for glioblastoma, but is poorly quantified. Here we define and characterize a novel neuroimaging parameter, lateral ventricle displacement (LVd), which quantifies mass effect in glioblastoma patients. LVd is defined as the magnitude of displacement from the center of mass of the lateral ventricle volume in glioblastoma patients relative to that a normal reference brain. Pre-operative MR images from 214 glioblastoma patients from The Cancer Imaging Archive (TCIA) were segmented using iterative probabilistic voxel labeling (IPVL). LVd, contrast enhancing volumes (CEV) and FLAIR hyper-intensity volumes (FHV) were determined. Associations with patient survival and tumor genomics were investigated using data from The Cancer Genome Atlas (TCGA). Glioblastoma patients had significantly higher LVd relative to patients without brain tumors. The variance of LVd was not explained by tumor volume, as defined by CEV or FLAIR. LVd was robustly associated with glioblastoma survival in Cox models which accounted for both age and Karnofsky's Performance Scale (KPS) (p = 0.006). Glioblastomas with higher LVd demonstrated increased expression of genes associated with tumor proliferation and decreased expression of genes associated with tumor invasion. Our results suggest LVd is a quantitative measure of glioblastoma mass effect and a prognostic imaging biomarker.

Background: Real-time magnetic resonance imaging (MRI) visualization during stereotactic needle biopsies affords several valuable benefits to the neurosurgeon, including the opportunity to visually confirm the biopsy site at the time of surgery. Until now, reported experiences with this technique have been limited to the setting of intraoperative MRI or dedicated procedural MRI suites with modified ventilation systems., Objective: To describe our experience with 11 consecutive patients who underwent real-time MRI-guided biopsy performed using SmartFrame® stereotaxis (MRI Interventions, Irvine, California) in the setting of a conventional diagnostic MRI suite., Methods: This is a case series of patients that underwent real-time MRI-guided biopsy at a single institution., Results: Four of the 11 lesions were previously biopsied by experienced neurosurgeons, yielding tissues that were nondiagnostic. Six of these lesions were sub-cubic centimeter in volume. One lesion was associated with aberrant venous anatomy. Two patients underwent laser thermal ablation in the same setting. There were no perioperative complications or unplanned 30-day readmission. All patients were discharged on postoperative day 1 to home. The operative time for the biopsy averaged 165 ± 24 min. Illustrative examples are reviewed., Conclusion: Real-time MRI-guided needle biopsy can be safely performed in the setting of a conventional diagnostic MRI suite. This technique provides neurosurgeons with the opportunity to visualize and confirm the biopsy site and allows for real-time adjustments in surgical maneuvers., (Copyright © 2017 by the Congress of Neurological Surgeons)

Frameless, surface imaging guided radiosurgery (SIG-RS) is a novel platform for stereotactic radiosurgery (SRS) wherein patient positioning is monitored in real-time through infra-red camera tracking of facial topography. Here we describe our initial clinical experience with SIG-RS for the treatment of benign neoplasms of the skull base. We identified 48 patients with benign skull base tumors consecutively treated with SIG-RS at a single institution between 2009 and 2011. Patients were diagnosed with meningioma (n = 22), vestibular schwannoma (n = 20), or nonfunctional pituitary adenoma (n = 6). Local control and treatment-related toxicity were retrospectively assessed. Median follow-up was 65 months (range 61-72 months). Prescription doses were 12-13 Gy in a single fraction (n = 18), 8 Gy × 3 fractions (n = 6), and 5 Gy × 5 fractions (n = 24). Actuarial tumor control rate at 5 years was 98%. No grade ≥3 treatment-related toxicity was observed. Grade ≤2 toxicity was associated with symptomatic lesions (p = 0.049) and single fraction treatment (p = 0.005). SIG-RS for benign skull base tumors produces clinical outcomes comparable to conventional frame-based SRS techniques while enhancing patient comfort.

Purpose: To review the utility of intraoperative imaging in facilitating maximal resection of non-functioning pituitary adenomas (NFAs)., Methods: We performed an exhaustive MEDLINE search, which yielded 5598 articles. Upon careful review of these studies, 31 were pertinent to the issue of interest., Results: Nine studies examined whether intraoperative MRI (iMRI) findings correlated with the presence of residual tumor on MRI taken 3 months after surgical resection. All studies using iMRI of >0.15T showed a ≥90% concordance between iMRI and 3-month post-operative MRI findings. 24 studies (22 iMRI and 2 intraoperative CT) examined whether intraoperative imaging improved the surgeon's ability to achieve a more complete resection. The resections were carried out under microscopic magnification in 17 studies and under endoscopic visualization in 7 studies. All studies support the value of intraoperative imaging in this regard, with improved resection in 15-83% of patients. Two studies examined whether iMRI (≥0.3T) improved visualization of residual NFA when compared to endoscopic visualization. Both studies demonstrated the value of iMRI in this regard, particularly when the tumor is located lateral of the sella, in the cavernous sinus, and in the suprasellar space., Conclusion: The currently available literature supports the utility of intraoperative imaging in facilitating increased NFA resection, without compromising safety.

Background: Frameless stereotactic radiosurgery is commonly used to treat intracranial metastases, but mask-based immobilization can be uncomfortable for patients., Objective: To describe the clinical outcomes using a novel real-time, frameless, surface imaging--guided radiosurgery (SIG-RS) technique to treat brain metastases., Methods: Data were prospectively gathered for 44 consecutive patients totaling 115 intracranial metastases treated with SIG-RS in a median of 1 fraction (range, 1-5) to a median dose of 20 Gy (range, 15-30 Gy). Local control, regional control, and overall survival were estimated by the Kaplan-Meier method., Results: Median follow-up for all patients was 6.0 months (range, 0.3-21.6 months), with 31 of 44 (70%) deceased at the time of analysis. The 35 patients (80%) with follow-up imaging totaled 88 lesions evaluable for local control. Actuarial 6- and 12-month local control was 90% (95% confidence interval, 82-98) and 76% (95% confidence interval, 60-91), respectively. Regional failure was observed in 16 patients (46%). The median actuarial overall survival was 7.7 months (95% confidence interval, 5.7-9.7). Analysis of the subset of 22 patients (55 lesions) who received SIG-RS alone (no prior treatment) in a single fraction yielded comparable clinical outcomes. Grade 3 or greater toxicity occurred in 4 patients (9%). The median treatment time from beam on to beam off was 15 minutes (range, 3-36 minutes)., Conclusion: SIG-RS for treating intracranial metastases can produce clinical outcomes comparable to those with conventional frame-based and frameless stereotactic radiosurgery techniques while providing greater patient comfort with an open-faced mask and fast treatment times.

Objective: Outcome studies in rodent tumor models rely on both histological and noninvasive study end points. Intracranial models require special tools to observe tumor growth over time noninvasively, such as magnetic resonance imaging (MRI), computed tomographic scanning, or cranial window techniques. These techniques share disadvantages in terms of cost, technical expertise required, and overall animal throughput for analysis. In this report, we sought to validate the use of the relatively newer technique of bioluminescence imaging (BLI) of intracranial glioblastoma xenograft growth by comparing it with gadolinium-enhanced MRI., Methods: U87MG glioma cell lines genetically engineered to express the firefly luciferase gene were stereotactically injected into nude mice in the left frontal lobe. Weekly BLI and MRI were performed after the inoculation of tumor cells. For BLI, tumor growth was assessed as the peak BLI after systemic injection of luciferin substrate. MRI-based growth curves were created by three-dimensional volumetric reconstruction of axial gadolinium-enhanced MRI data covering the whole brain. In a separate experiment, mice were treated with adenoviruses encoding antiangiogenic soluble vascular endothelial growth factor receptors, and treatment effect was monitored by BLI., Results: Untreated tumor growth was readily detected and observed over time by serial BLI measurements. Furthermore, tumor-derived light emission was highly correlated with volume of tumor as assessed by MRI. Furthermore, the tested antiangiogenic treatment effect was readily detected using this technique, suggesting the power of the technique for sensitive monitoring of novel therapeutics., Conclusion: BLI offers a simple and rapid technique for assessing intracranial glioblastoma growth in rodent models noninvasively, which correlates well with MRI. The speed of the BLI technique can increase experimental throughput, allows for targeted histological analysis in animals showing the greatest treatment effects, and provides new insights into the kinetics of intracranial tumor growth in the setting of different treatments.

The physiologic processes underlying MRI contrast enhancement in glioblastoma patients remain poorly understood. MRIs of 148 glioblastoma subjects from The Cancer Imaging Archive were segmented using Iterative Probabilistic Voxel Labeling (IPVL). Three aspects of contrast enhancement (CE) were parametrized: the mean intensity of all CE voxels (CEi), the intensity heterogeneity in CE (CEh), and volumetric ratio of CE to necrosis (CEr). Associations between these parameters and patterns of gene expression were analyzed using DAVID functional enrichment analysis. Glioma CpG island methylator phenotype (G-CIMP) glioblastomas were poorly enhancing. Otherwise, no differences in CE parameters were found between proneural, neural, mesenchymal, and classical glioblastomas. High CEi was associated with expression of genes that mediate inflammatory responses. High CEh was associated with increased expression of genes that regulate remodeling of extracellular matrix (ECM) and endothelial permeability. High CEr was associated with increased expression of genes that mediate cellular response to stressful metabolic states, including hypoxia and starvation. Our results indicate that CE in glioblastoma is associated with distinct biological processes involved in inflammatory response and tissue hypoxia. Integrative analysis of these CE parameters may yield meaningful information pertaining to the biologic state of glioblastomas and guide future therapeutic paradigms.

IntroductionThe subventricular zone (SVZ) has been implicated in the pathogenesis of glioblastoma. Whether molecular subtypes of glioblastoma arise from unique niches of the brain relative to the SVZ remains largely unknown. Here, we tested whether these subtypes of glioblastoma occupy distinct regions of the cerebrum and examined glioblastoma localization in relation to the SVZ.MethodsPre-operative MR images from 217 glioblastoma patients from The Cancer Imaging Archive were segmented automatically into contrast enhancing (CE) tumor volumes using Iterative Probabilistic Voxel Labeling (IPVL). Probabilistic maps of tumor location were generated for each subtype and distances were calculated from the centroid of CE tumor volumes to the SVZ. Glioblastomas that arose in a Genetically Modified Murine Model (GEMM) model were also analyzed with regard to SVZ distance and molecular subtype.ResultsClassical and mesenchymal glioblastomas were more diffusely distributed and located farther from the SVZ. In contrast, proneural and neural glioblastomas were more likely to be located in closer proximity to the SVZ. Moreover, in a GFAP-CreER; PtenloxP/loxP; Trp53loxP/loxP; Rb1loxP/loxP; Rbl1-/- GEMM model of glioblastoma where tumor can spontaneously arise in different regions of the cerebrum, tumors that arose near the SVZ were more likely to be of proneural subtype (p < 0.0001).ConclusionsGlioblastoma subtypes occupy different regions of the brain and vary in proximity to the SVZ. These findings harbor implications pertaining to the pathogenesis of glioblastoma subtypes.

Introduction: Diffusion Weighted Imaging (DWI), which is based on Echo Planar Imaging (EPI) protocols, is becoming increasingly important for neurosurgical applications. However, its use in this context is limited in part by significant spatial distortion inherent to EPI. Method: We evaluated an efficient algorithm for EPI distortion correction (EPIC) across 814 DWI scans from 250 brain tumor patients and quantified the magnitude of geometric distortion for whole brain and multiple brain regions. Results: Evaluation of the algorithm’s performance revealed significantly higher mutual information between T1-weighted pre-contrast images and corrected b = 0 images than the uncorrected b = 0 images (p < 0.001). The distortion magnitude across all voxels revealed a median EPI distortion effect of 2.1 mm, ranging from 1.2 mm to 5.9 mm, the 5th and 95th percentile, respectively. Regions adjacent to bone-air interfaces, such as the orbitofrontal cortex, temporal poles, and brain stem, were the regions most severely affected by DWI distortion. Conclusion: Using EPIC to estimate the degree of distortion in 814 DWI brain tumor images enabled the creation of a topographic atlas of DWI distortion across the brain. The degree of displacement of tumors boundaries in uncorrected images is severe but can be corrected for using EPIC. Our results support the use of distortion correction to ensure accurate and careful application of DWI to neurosurgical practice. [ABSTRACT FROM AUTHOR]

We examined the extracellular vesicle (EV) and RNA composition of pooled normal cerebrospinal fluid (CSF) samples and CSF from five major neurological disorders: Alzheimer’s disease (AD), Parkinson’s disease (PD), low-grade glioma (LGG), glioblastoma multiforme (GBM), and subarachnoid haemorrhage (SAH), representing neurodegenerative disease, cancer, and severe acute brain injury. We evaluated: (I) size and quantity of EVs by nanoparticle tracking analysis (NTA) and vesicle flow cytometry (VFC), (II) RNA yield and purity using four RNA isolation kits, (III) replication of RNA yields within and between laboratories, and (IV) composition of total and EV RNAs by reverse transcription–quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing (RNASeq). The CSF contained ~106 EVs/μL by NTA and VFC. Brain tumour and SAH CSF contained more EVs and RNA relative to normal, AD, and PD. RT-qPCR and RNASeq identified disease-related populations of microRNAs and messenger RNAs (mRNAs) relative to normal CSF, in both total and EV fractions. This work presents relevant measures selected to inform the design of subsequent replicative CSF studies. The range of neurological diseases highlights variations in total and EV RNA content due to disease or collection site, revealing critical considerations guiding the selection of appropriate approaches and controls for CSF studies. [ABSTRACT FROM PUBLISHER]

Background The phenomenon of intracerebral schwannoma is exceedingly rare, and its etiology still a matter of debate. No documented cases of intracerebral schwannoma containing vascular elements consistent with those of an arteriovenous malformation (AVM) have been reported. We describe such a case here. Case Description A left temporal intraparenchymal lesion was discovered incidentally in a 34-year-old man after he suffered a mild trauma. The lesion was resected and found on histologic examination to be an intracerebral schwannoma with AVM-like vasculature. The patient made a full recovery after resection. Conclusions To our knowledge, this is the first case of an intracerebral schwannoma with AVM-like characteristics to be reported in the literature. We hypothesize that the co-occurrence of this rare pathologic entity is caused by an interrelated etiologic process, with the tumor microenvironment of the schwannoma inciting the development of the vascular malformation. [ABSTRACT FROM AUTHOR]