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Background Prevalence, radiological characteristics, and risk factors for peritumoral infarctions after glioma surgery are not much studied. In this study, we assessed shape, volume, and prevalence of peritumoral infarctions and investigated possible associated factors. Methods In a prospective single-center cohort study, we included all adult patients operated for diffuse gliomas from January 2007 to December 2018. Postoperative infarctions were segmented using early postoperative MRI images, and volume, shape, and location of postoperative infarctions were assessed. Heatmaps of the distribution of tumors and infarctions were created. Results MRIs from 238 (44%) of 539 operations showed restricted diffusion in relation to the operation cavity, interpreted as postoperative infarctions. Of these, 86 (36%) were rim-shaped, 103 (43%) were sector-shaped, 40 (17%) were a combination of rim- and sector-shaped, and six (3%) were remote infarctions. Median infarction volume was 1.7 cm3 (IQR 0.7–4.3, range 0.1–67.1). Infarctions were more common if the tumor was in the temporal lobe, and the map shows more infarctions in the periventricular watershed areas. Sector-shaped infarctions were more often seen in patients with known cerebrovascular disease (47.6% vs. 25.5%, p = 0.024). There was a positive correlation between infarction volume and tumor volume (r = 0.267, p Conclusions In the present study, peritumoral infarctions occurred in 44% after diffuse glioma operations. Infarctions were more common in patients operated for tumors in the temporal lobe but were not more common following recurrent surgeries. Sector-shaped infarctions were more common in patients with known cerebrovascular disease. Increasing age, larger tumors, and more perioperative bleeding were factors associated with infarction volumes. The risk of infarctions and infarction volumes may also be surgeon-dependent.

Background Patients with metastatic cancer to the brain have a poor prognosis. In clinical practice, MRI is used to delineate, diagnose and plan treatment of brain metastases. However, MRI alone is limited in detecting micro-metastases, delineating lesions and discriminating progression from pseudo-progression. Combined PET/MRI utilises superior soft tissue images from MRI and metabolic data from PET to evaluate tumour structure and function. The amino acid PET tracer 18F-FACBC has shown promising results in discriminating high- and low-grade gliomas, but there are currently no reports on its use on brain metastases. This is the first study to evaluate the use of 18F-FACBC on brain metastases. Case presentation A middle-aged female patient with brain metastases was evaluated using hybrid PET/MRI with 18F-FACBC before and after stereotactic radiotherapy, and at suspicion of recurrence. Static/dynamic PET and contrast-enhanced T1 MRI data were acquired and analysed. This case report includes the analysis of four 18F-FACBC PET/MRI examinations, investigating their utility in evaluating functional and structural metastasis properties. Conclusion Analysis showed high tumour-to-background ratios in brain metastases compared to other amino acid PET tracers, including high uptake in a very small cerebellar metastasis, suggesting that 18F-FACBC PET can provide early detection of otherwise overlooked metastases. Further studies to determine a threshold for 18F-FACBC brain tumour boundaries and explore its utility in clinical practice should be performed.

Purpose Previous studies on the effect of tumor location on overall survival in glioblastoma have found conflicting results. Based on statistical maps, we sought to explore the effect of tumor location on overall survival in a population-based cohort of patients with glioblastoma and IDH wild-type astrocytoma WHO grade II–III with radiological necrosis. Methods Patients were divided into three groups based on overall survival: < 6 months, 6–24 months, and > 24 months. Statistical maps exploring differences in tumor location between these three groups were calculated from pre-treatment magnetic resonance imaging scans. Based on the results, multivariable Cox regression analyses were performed to explore the possible independent effect of centrally located tumors compared to known prognostic factors by use of distance from center of the third ventricle to contrast-enhancing tumor border in centimeters as a continuous variable. Results A total of 215 patients were included in the statistical maps. Central tumor location (corpus callosum, basal ganglia) was associated with overall survival < 6 months. There was also a reduced overall survival in patients with tumors in the left temporal lobe pole. Tumors in the dorsomedial right temporal lobe and the white matter region involving the left anterior paracentral gyrus/dorsal supplementary motor area/medial precentral gyrus were associated with overall survival > 24 months. Increased distance from center of the third ventricle to contrast-enhancing tumor border was a positive prognostic factor for survival in elderly patients, but less so in younger patients. Conclusions Central tumor location was associated with worse prognosis. Distance from center of the third ventricle to contrast-enhancing tumor border may be a pragmatic prognostic factor in elderly patients.

O6-methylguanine DNA methyltransferase (MGMT) promoter methylation is an important favorable predictive marker in patients with glioblastoma (GBM). We hypothesized that MGMT status could be a surrogate marker of pretreatment tumor biology observed as histopathological and radiological features. Apart from some radiological studies aiming to noninvasively predict the MGMT status, few studies have investigated relationships between MGMT status and phenotypical tumor biology. We have therefore aimed to investigate such relationships in 85 isocitrate dehydrogenase (IDH) wild-type GBMs. MGMT status was determined by methylation-specific PCR and was assessed for associations with 22 histopathological features, immunohistochemical proliferative index and microvessel density measurements, conventional magnetic resonance imaging characteristics, preoperative speed of tumor growth, and overall survival. None of the investigated histological or radiological features were significantly associated with MGMT status. Methylated MGMT status was a significant independent predictor of improved overall survival. In conclusion, our results suggest that MGMT status is not related to the pretreatment phenotypical biology in IDH wild-type GBMs. Furthermore, our findings suggest the survival benefit of MGMT methylated GBMs is not due to an inherently less aggressive tumor biology, and that conventional magnetic resonance imaging features cannot be used to noninvasively predict the MGMT status. VC 2020 American Association of Neuropathologists, Inc. 855 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Background The otic ganglion (OG) provides parasympathetic innervation to the cerebral circulation and cranial structures and may be involved in the pathophysiology of trigeminal autonomic headaches. This structure has never been targeted in any headache disorder. Objective To investigate the safety of injecting onabotulinumtoxin A (BTA) toward the OG in 10 patients with intractable chronic cluster headache and to collect efficacy data. Methods A total of 10 patients with chronic cluster headache were enrolled in this open-label, multi-dose pilot safety study. All patients were recruited and treated on an out-patient basis at St Olav's University Hospital (Norway). In 5 patients each, the OG was the injection target with 12.5 IU of BTA or 25 IU, respectively. The primary outcome measure was adverse events (AEs) and the main secondary outcome was the number of attacks per week measured at baseline and in the second month following injection. Results For the primary endpoint, we analyzed data for all 10 patients. There were a total of 17 AEs in 6 of the 10 patients. All AEs were considered mild and disappeared by the end of follow-up. The median number of attacks per week at baseline was 17.0 [7.8 to 25.8] vs 14.0 [7.3 to 20.0] in the second month following injection; difference: 3 (95%CI: -0.3 to 7.9), P = .063. Conclusions Injection with BTA toward the OG appears to be safe. We did not find a statistically significant reduction in the number of attacks per week at month 2 after injection compared to the baseline. This study suggests that the OG is not an important target for the treatment of chronic cluster headache. A future study employing more precise targeting of the OG may be indicated.

Rationale and Objectives Team-based learning (TBL) is a student-centred, teacher-directed instructional method that promotes active learning. The application phase of TBL stimulates group discussion and critical thinking, which could be useful for learning radiology. We designed and evaluated two modified TBL-sessions on computed tomography and magnetic resonance imaging diagnostics in neuroradiology. Our aim was to examine what effects engaging students in in-class team application tasks had on student learning. Materials and Methods A cross-over study was conducted, including 105 third-year medical students using two modified TBL sessions as the active learning intervention compared with two traditional lectures as a control. Student learning was assessed by results on the neuroradiology part of the end-of-year written examination. Student engagement and perceptions were assessed using the Student Self-Report of Engagement Measure and an additional four Likert-type items. Results There were no statistically significant differences in student scores on the examination. Students reported high levels of engagement, and reported being more satisfied overall with the TBL sessions than traditional lectures. Students rated the TBL sessions higher than lectures on ability to make difficult material comprehensible, ability to engage students and to give them feedback. Conclusion The modified TBL sessions halved in-class teaching time and by omitting the readiness assurance tests, there was more in-class time to focus on problem-solving of real clinical cases. Moreover, shorter sessions may ease implementation of TBL in the curriculum and allow for more frequent sessions. Students were more satisfied with eTBL than lectures, and reported high levels of engagement.

Purpose To assess the ability of 7 T MRI to detect hippocampal DWI lesions in the acute phase of TGA compared to 1.5 T/3 T MRI. Methods Patients with a clinical diagnosis consistent with TGA and a 1.5/3 T MRI underwent an additional 7 T MRI when the 7 T system was available for clinical use, thus serving as their own controls. Results Thirteen TGA patients with a median age of 68.5 years (range 46–77 years) were included and imaged at 1.5/3 T (median 17 h after onset of symptoms, range 3–23 h) and 7 T (median 23 h after onset, range 15–46 h). The 7 T MRIs were performed a median of 15 h after the 1.5/3 T MRIs (range 1–28 h). At 1.5/3 T, six patients (46%) were found to have at least one hippocampal DWI-lesions supporting the TGA diagnosis, which increased to 11 patients (85%) when examined at 7 T (p = 0.03). At 1.5/3 T, nine hippocampal DWI lesions were detected, which increased to 19 at 7 T, giving an increased detection rate of 111% (p = 0.002). Both neuroradiologists found the hippocampal DWI lesions at 7 T to have higher conspicuity and be easier to categorize as true findings compared to 1.5/3 T. Conclusion Seven-Tesla MRI showed both a statistically significant increase in the total number of detected hippocampal DWI lesions and the proportion of patients with at least one hippocampal DWI lesion supporting the TGA diagnosis compared to 1.5/3 T. Clinical use of 7 T will increase the number of patients having their TGA diagnosis supported by MRI, which can be especially useful in patients with negative 1.5/3 T MRI and low clinical certainty.

Purpose This pilot study aimed to evaluate the amino acid tracer 18F-FACBC with simultaneous PET/MRI in diagnostic assessment and neurosurgery of gliomas. Materials and Methods Eleven patients with suspected primary or recurrent low- or high-grade glioma received an 18F-FACBC PET/MRI examination before surgery. PET and MRI were used for diagnostic assessment, and for guiding tumor resection and histopathological tissue sampling. PET uptake, tumor-to-background ratios (TBRs), time-activity curves, as well as PET and MRI tumor volumes were evaluated. The sensitivities of lesion detection and to detect glioma tissue were calculated for PET, MRI, and combined PET/MRI with histopathology (biopsies for final diagnosis and additional image-localized biopsies) as reference. Results Overall sensitivity for lesion detection was 54.5% (95% confidence interval [CI], 23.4–83.3) for PET, 45.5% (95% CI, 16.7–76.6) for contrast-enhanced MRI (MRICE), and 100% (95% CI, 71.5–100.0) for combined PET/MRI, with a significant difference between MRICE and combined PET/MRI (P = 0.031). TBRs increased with tumor grade (P = 0.004) and were stable from 10 minutes post injection. PET tumor volumes enclosed most of the MRICE volumes (>98%) and were generally larger (1.5–2.8 times) than the MRICE volumes. Based on image-localized biopsies, combined PET/MRI demonstrated higher concurrence with malignant findings at histopathology (89.5%) than MRICE (26.3%). Conclusions Low- versus high-grade glioma differentiation may be possible with 18F-FACBC using TBR. 18F-FACBC PET/MRI outperformed MRICE in lesion detection and in detection of glioma tissue. More research is required to evaluate 18F-FACBC properties, especially in grade II and III tumors, and for different subtypes of gliomas. © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

Purpose The main aim of this study was to provide normative data for pituitary height and volume in persons between 50 and 66 years in the general population. The secondary aim was to establish a convenient surrogate marker of pituitary size for use in routine radiological practice. Methods From a geographically defined prospective healthy study, 1006 participants between 50 and 66 years had a brain MRI, of which 988 (519 women) were included in this study. We measured the mid-sagittal height, max-sagittal height and total volume of the anterior pituitary lobe based on T1-weighted 3D MRI images. Results Both the mean mid-sagittal and max-sagittal pituitary height were significantly larger in women compared to men, with 4.9 ± 1.7 mm versus 4.4 ± 1.4 mm (p 3 vs. 405 ± 118 mm3) (p 3 for women and 6.6 mm, 7.8 mm and 610 mm3 for men. Conclusion This study show that women have a larger pituitary gland than men in the age group between 50 and 66 years and provides normative data for pituitary size estimates which can be used for clinical diagnostic purposes as well as future research.

Introduction According to the stem cell theory, two neurogenic niches in the adult human brain may harbor cells that initiate the formation of gliomas: The larger subventricular zone (SVZ) and the subgranular zone (SGZ) in the hippocampus. We wanted to explore whether defining molecular markers in low-grade gliomas (LGG; WHO grade II) are related to distance to the neurogenic niches. Methods Patients treated at two Norwegian university hospitals with population-based referral were included. Eligible patients had histopathological verified supratentorial low-grade glioma. IDH mutational status and 1p19q co-deletion status was retrospectively assessed. 159 patients were included, and semi-automatic tumor segmentation was done from pre-treatment T2-weighted (T2W) or Fluid-Attenuated Inversion Recovery (FLAIR) images. 3D maps showing the anatomical distribution of the tumors were then created for each of the three molecular subtypes (IDH mutated/1p19q co-deleted, IDH mutated and IDH wild-type). Both distance from tumor center and tumor border to the neurogenic niches were recorded. Results In this population-based cohort of previously untreated low-grade gliomas, we found that low-grade gliomas are more often found closer to the SVZ than the SGZ, but IDH wild-type tumors are more often found near SGZ. Conclusion Our study suggests that the stem cell origin of IDH wild-type and IDH mutated low-grade gliomas may be different.

Background The preoperative growth of human glioblastomas (GBMs) has been shown to vary among patients. In animal studies, angiogenesis has been linked to hypoxia and faster growth of GBM, however, its relation to the growth of human GBMs is sparsely studied. We have therefore aimed to look for associations between radiological speed of growth and microvessel density (MVD) counts of the endothelial markers vWF (Factor VIII related antigen) and CD105 (endoglin). Methods Preoperative growth was estimated from segmented tumor volumes of two preoperative T1-weighted postcontrast magnetic resonance imaging scans taken ≥14 days apart in patients with newly diagnosed GBMs. A Gompertzian growth curve was computed from the volume data and separated the patients into two groups of either faster or slower tumor growth than expected. MVD counts of the immunohistochemical markers von Willebrand factor (vWF) (a pan-endothelial marker) and CD105 (a marker of proliferating endothelial cells) were assessed for associations with fast-growing tumors using Mann-Whitney U tests and a multivariable binary logistic regression analysis. Results We found that only CD105-MVD was significantly associated with faster growth in a univariable analysis (p = 0.049). However, CD105-MVD was no longer significant when corrected for the presence of thromboses and high cellular density in a multivariable model, where the latter features were significant independent predictors of faster growth with respective odds ratios 4.2 (95% confidence interval, 1.2, 14.3), p = 0.021 and 2.6 (95% confidence interval, 1.0, 6.5), p = 0.048. Conclusions MVDs of neither endothelial marker were independently associated with faster growth, suggesting angiogenesis-independent processes contribute to faster glioblastoma growth. © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)

Detection of progression is clinically important for the management of glioblastoma. We sought to assess the accuracy of clinical radiological reporting and measured bidimensional products to identify radiological glioblastoma progression. The two were compared to volumetric segmentation. In this retrospective study, we included 106 patients with histopathologically verified glioblastomas and two separate MRI scans obtained before surgery. Bidimensional products based on measurements on the axial slice with the largest tumor area were calculated, and growth estimations from the clinical radiological reports were retrieved. The two growth estimations were compared to manual volumetric segmentations. Inter-observer agreement using the bidimensional product was assessed using Kappa-statistics and by calculating the difference between two neuroradiologist in percentage change of the bidimensional product for each tumor. Clinical radiological reports and bidimensional products showed fairly equal accuracy when compared to volumetric segmentation with an accuracy of 67% and 66–68%, respectively. There was a difference in median volume increase of 6.9 mL (2.4 vs 9.3 mL, p < 0.001) between tumors evaluated as stable and progressed based on the clinical radiological reports. This difference was 8.1 mL (2.0 vs 10.1 ml, p < 0.001) when using the bidimensional products. The bidimensional product reached a moderate inter-observer agreement with a Kappa value of 0.689. For 32% of the tumors, the two neuroradiologists calculated a difference of more than 25% using bidimensional products. Clinical radiological reporting and the bidimensional product exhibit similar accuracy. The bidimensional product has moderate inter-observer agreement and is prone to underestimating tumor progression, as an average glioblastoma had to grow 10 mL in order to be classified as progressed. These findings underline the assumption that one should try to move towards volumetric assessment of glioblastoma growth in the future.

Background: Positron emission tomography/magnetic resonance imaging (PET/MRI) is a promising diagnostic imaging tool for the diagnosis of dementia, as PET can add complementary information to the routine imaging examination with MRI. The purpose of this study was to evaluate the influence of MRI-based attenuation correction (MRAC) on diagnostic assessment of dementia with [18F]FDG PET. Quantitative differences in both [18F]FDG uptake and z-scores were calculated for three clinically available (DixonNoBone, DixonBone, UTE) and two research MRAC methods (UCL, DeepUTE) compared to CT-based AC (CTAC). Furthermore, diagnoses based on visual evaluations were made by three nuclear medicine physicians and one neuroradiologist (PETCT, PETDeepUTE, PETDixonBone, PETUTE, PETCT + MRI, PETDixonBone + MRI). In addition, pons and cerebellum were compared as reference regions for normalization. Results: The mean absolute difference in z-scores were smallest between MRAC and CTAC with cerebellum as reference region: 0.15 ± 0.11 σ (DeepUTE), 0.15 ± 0.12 σ (UCL), 0.23 ± 0.20 σ (DixonBone), 0.32 ± 0.28 σ (DixonNoBone), and 0.54 ± 0.40 σ (UTE). In the visual evaluation, the diagnoses agreed with PETCT in 74% (PETDeepUTE), 67% (PETDixonBone), and 70% (PETUTE) of the patients, while PETCT + MRI agreed with PETDixonBone + MRI in 89% of the patients. Conclusion: The MRAC research methods performed close to that of CTAC in the quantitative evaluation of [18F]FDG uptake and z-scores. Among the clinically implemented MRAC methods, DixonBone should be preferred for diagnostic assessment of dementia with [18F]FDG PET/MRI. However, as artifacts occur in DixonBone attenuation maps, they must be visually inspected to assure proper quantification.

OBJECTIVEExtent of resection (EOR) and residual tumor volume are linked to prognosis in low-grade glioma (LGG) and there are various methods for facilitating safe maximal resection in such patients. In this prospective study the authors assess radiological and clinical results in consecutive patients with LGG treated with 3D ultrasound (US)–guided resection under general anesthesia.METHODSConsecutive LGGs undergoing primary surgery guided with 3D US between 2008 and 2015 were included. All LGGs were classified according to the WHO 2016 classification system. Pre- and postoperative volumetric assessments were performed, and volumetric results were linked to overall and malignant-free survival. Pre- and postoperative health-related quality of life (HRQoL) was evaluated.RESULTSForty-seven consecutive patients were included. Twenty LGGs (43%) were isocitrate dehydrogenase (IDH)–mutated, 7 (14%) were IDH wild-type, 19 (40%) had both IDH mutation and 1p/19q codeletion, and 1 had IDH mutation and inconclusive 1p/19q status. Median resection grade was 93.4%, with gross-total resection achieved in 14 patients (30%). An additional 24 patients (51%) had small tumor remnants < 10 ml. A more conspicuous tumor border (p = 0.02) and lower University of California San Francisco prognostic score (p = 0.01) were associated with less remnant tumor tissue, and overall survival was significantly better with remnants < 10 ml (p = 0.03). HRQoL was maintained or improved in 86% of patients at 1 month. In both cases with severe permanent deficits, relevant ischemia was present on diffusion-weighted postoperative MRI.CONCLUSIONSThree-dimensional US–guided LGG resections under general anesthesia are safe and HRQoL is preserved in most patients. Effectiveness in terms of EOR appears to be consistent with published studies using other advanced neurosurgical tools. Avoiding intraoperative vascular injury is a key factor for achieving good functional outcome.

Objectives Observational data on the natural course of tumor growth in humans is sparse, and mathematical models of tumor growth are often needed to answer questions related to growth. In this study, a theoretical model of glioblastoma growth was used to investigate two questions often asked by patients and clinicians. First, when did the tumor start growing? Second, how much survival time can be gained from various extents of surgical resection (EOR)?. Patients and methods A gompertzian growth curve was fitted from observational data of pre-treatment growth from 106 glioblastoma patients based on repeated volume segmentations. The curve was used to find the theoretical time since tumor initiation. In addition, as a proxy for the potential survival gain from surgery, the number of days until re-growth would reach the preoperative tumor volume were calculated for different extents of resection. Results The estimated age of the glioblastomas at diagnosis was median 330 days, but ranging from 156 days to 776 days, depending on the tumor volume at diagnosis. The median survival gains from 50%, 75%, 90%, 95% and 99% EOR were, 1.4, 2.5, 3.6, 4.3, and 5.6 months, respectively. However, survival benefit from surgery also depends on lesion volume. In theory, 100 days may be gained from 95% EOR in a 10 mL lesion or a 50% EOR in a 90 ml lesion. Conclusion In conclusion, we postulate that glioblastoma might originate median 330 days before the diagnosis, assuming the same growth pattern and biology from day one. The theoretical survival benefit of glioblastoma resection is much higher with higher EORs, suggesting that the last milliliters of resection matter the most. Our data also suggest that gain from resection is higher in larger lesions, suggesting that lesion volume may be taken into account in clinical decision-making.

Generating MR-derived growth pattern models for glioblastoma multiforme (GBM) has been an attractive approach in neuro-oncology, suggesting a distinct pattern of lesion spread with a tendency in growing along the white matter (WM) fibre direction for the invasive component. However, the direction of growth is not much studied in vivo. In this study, we sought to study the dominant directions of tumour expansion/shrinkage pre-treatment. We examined fifty-six GBMs at two time-points: at radiological diagnosis and as part of the pre-operative planning, both with contrast-enhanced T1-weighted MRIs. The tumour volumes were semi-automatically segmented. A non-linear registration resulting in a deformation field characterizing the changes between the two time points was used together with the segmented tumours to determine the dominant directions of tumour change. To compute the degree of alignment between tumour growth vectors and WM fibres, an angle map was calculated. Our results demonstrate that tumours tend to grow predominantly along the WM, as evidenced by the dominant vector population with the maximum alignments. Our findings represent a step forward in investigating the hypothesis that tumour cells tend to migrate preferentially along the WM. © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)

Methods. By using repeated pretreatment contrast-enhanced T1-weighted MRI scans from 106 patients (aged 26–83 years), we studied the growth dynamics of untreated glioblastomas in vivo. Growth rates were calculated as specific growth rates and equivalent volume doubling times. The fit of different possible growth models was assessed using maximum likelihood estimations. Results. There were large variations in growth rates between patients. The median specific growth rate of the tumors was 1.4% per day, and the equivalent volume doubling time was 49.6 days. Exploring 3 different tumor growth models showed similar statistical fit for a Gompertzian growth model and a linear radial growth model and worse fit for an exponential growth model. However, large tumors had significantly lower growth rates than smaller tumors, supporting the assumption that glioblastomas reach a plateau phase and thus exhibit Gompertzian growth. Conclusion. Based on the fast growth rate of glioblastoma shown in this study, it is evident that poor treatment logistics will influence tumor size before surgery and can cause significant regrowth before adjuvant treatment. Since there is a known association between tumor volume, extent of surgical resection, and response to adjuvant therapy, it is likely that waiting times play a role in patient outcomes.

Structural magnetic resonance imaging (MRI) and histopathologic tissue sampling are routinely performed as part of the diagnostic workup for patients with glioma. Because of the heterogeneous nature of gliomas, there is a risk of undergrading caused by histopathologic sampling errors. MRI has limitations in identifying tumor grade and type, detecting diffuse invasive growth, and separating recurrences from treatment induced changes. Positron emission tomography (PET) can provide quantitative information of cellular activity and metabolism, and may therefore complement MRI. In this report, we present the first patient with brain glioma examined with simultaneous PET/MRI using the amino acid tracerA previously healthy 60-year old woman was admitted to the emergency care with speech difficulties and a mild left-sided hemiparesis. MRI revealed a tumor that was suggestive of glioma. Before surgery, the patient underwent a simultaneous PET/MRI examination. Fused PET/MRI, T1, FLAIR, and intraoperative three-dimensional ultrasound images were used to guide histopathologic tissue sampling and surgical resection. Navigated, image-guided histopathologic samples were compared with PET/MRI image data to assess the additional value of the PET acquisition. Histopathologic analysis showed anaplastic oligodendroglioma in the most malignant parts of the tumor, while several regions were World Health Organization (WHO) grade II.

Objectives Molecular markers provide valuable information about treatment response and prognosis in patients with low-grade gliomas (LGG). In order to make this important information available prior to surgery the aim of this study was to explore if molecular status in LGG can be discriminated by preoperative magnetic resonance imaging (MRI). Patients and methods All patients with histopathologically confirmed LGG with available molecular status who had undergone a preoperative standard clinical MRI protocol using a 3T Siemens Skyra scanner during 2008–2015 were retrospectively identified. Based on Haralick texture parameters and the segmented LGG FLAIR volume we explored if it was possible to predict molecular status. Results In total 25 patients (nine women, average age 44) fulfilled the inclusion parameters. The textural parameter homogeneity could discriminate between LGG patients with IDH mutation (0.12, IQR 0.10-0.15) and IDH wild type (0.07, IQR 0.06-0.09, p = 0.005). None of the other four analyzed texture parameters (energy, entropy, correlation and inertia) were associated with molecular status. Using ROC curves, the area under curve for predicting IDH mutation was 0.905 for homogeneity, 0.840 for tumor volume and 0.940 for the combined parameters of tumor volume and homogeneity. We could not predict molecular status using the four other chosen texture parameters (energy, entropy, correlation and inertia). Further, we could not separate LGG with IDH mutation with or without 1p19q codeletion. Conclusions In this preliminary study using Haralick texture parameters based on preoperative clinical FLAIR sequence, the homogeneity parameter could separate IDH mutated LGG from IDH wild type LGG. Combined with tumor volume, these diagnostic properties seem promising. © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).

OBJECTIVES Identification of eloquent brain areas in patients with intra-axial lesions is important to minimize the risk of neurological deficit. We performed a multicenter study comparing conventional 2-dimensional magnetic resonance imaging (MRI) for identification of the central sulcus to topographical MRI and blood-oxygenation-level-dependent functional MRI (BOLD-fMRI). METHODS Seventy-seven unoperated patients with brain lesions were imaged at 1.5 or 3 T. The central sulcus was identified by an experienced neuroradiologist on 2-dimensional MRI, by topographic analysis of 3-dimensional MRI in BrainVoyager, and by BOLD-fMRI analysis in BrainVoyager or SPM5. RESULTS The central sulcus in the affected hemisphere was readily identified in a significantly higher percentage of patients by 2-dimensional MRI and topographical analysis (77/77 patients) compared to BOLD-fMRI (57 patients; P < 0.001). The topographical analysis identified a significantly larger portion of the total central sulcus than 2-dimensional MRI (P < 0.05). No differences were found between institutions, histological versus radiological diagnoses, MRI sequence parameters, age, or sex. CONCLUSIONS Identification of the central sulcus is best performed using topographical analysis; however, 2-dimensional analysis may suffice for daily routine work.

BACKGROUND: Human glioblastomas (GBMs) are highly angiogenic tumors characterized by a rapid tumor growth. In radiological studies, the preoperative speed of growth of treatment-naïve human GBMs varies considerably among patients. Faster GBM growth has been related to increased angiogenesis and hypoxia in animal models; however, such links have been sparsely studied in human patients. We have therefore aimed to look for associations between microvessel density (MVD) counts by means of two endothelial markers and radiological speed of growth. MATERIAL AND METHODS: In 102 patients with newly diagnosed GBMs, MVDs were counted using immunohistochemical staining of von Willebrand factor (vWF, factor VIII), a pan-endothelial marker, and CD105 (endoglin), a marker of proliferating endothelial cells. Radiological speed of growth was estimated from preoperative tumor volumes on two contrast-enhanced T1-weighted MRI scans taken ≥14 days apart. Because speed of growth has previously been shown to be highly associated with initial tumor volume, an expected Gompertzian growth curve fitted from the volume data and the interval between the scans was used to dichotomize the patients into two groups; tumors with a larger or smaller volume increase than expected from the curve (i. e. faster or slower growing tumors, respectively). These groups were assessed for associations with the MVDs using Mann-Whitney U tests and a multivariable binary logistic regression analysis, which included histopathological features previously found to independently predict faster GBM growth. RESULTS: CD105-MVD was the only marker significantly associated with faster growth in a univariable analysis (P = 0.049). However, when corrected for the presence of thromboses and high cellular density in a multivariable model, CD105-MVD was no longer significant. In this model, thromboses and high cellular density were significant independent predictors of faster growth with OR 4.2 (95% CI 1.2–14.3, P = 0.021) and OR 2.6 (95% CI 1.0–6.5, P = 0.048), respectively. CONCLUSION: Our results show that vWF-MVD and CD105-MVD are not independently associated with faster GBM growth, suggesting faster GBM growth is also driven by angiogenesis-independent processes.

Background Glioblastomas are highly aggressive and heterogeneous tumors, both in terms of patient outcome and molecular profile. Magnetic resonance imaging of tumor growth could potentially reveal new insights about tumor biology noninvasively. The aim of this exploratory retrospective study was to investigate the prognostic potential of pretreatment growth rate of glioblastomas, after controlling for known prognostic factors. Methods A growth model derived from clinical pretreatment postcontrast T1-weighted magnetic resonance imaging images was used to divide 106 glioblastoma patients into 2 groups. The “faster growth” group had tumors growing faster than expected based on their volume at diagnosis, whereas the “slower growth” group had tumors growing slower than expected. Associations between tumor growth and survival were examined by the use of multivariable Cox regression and logistic regression. Results None of the known prognostic factors were significantly associated with tumor growth. An extended multivariable Cox model showed that during the first 12 months of follow-up, there was no significant difference in survival between faster and slower growing tumors. Beyond 12 months' follow-up, however, there was a significant, independent survival benefit in having a tumor with slower pretreatment growth. In a multiple logistic regression model including patients receiving both radiotherapy and chemotherapy (n = 82), slower pre-treatment growth of the tumor was shown to be a significant predictor of 2-year survival (odds ratio 4.4). Conclusions Pretreatment glioblastoma growth harbors prognostic information. Patients with slower growing tumors have higher odds of survival beyond 2 years, adjusted for other prognostic factors.

Image guidance based on magnetic resonance imaging (MRI) and/or ultrasound (US) is widely used to aid decision making in glioma surgery, but tumor delineation based on these 2 modalities does not always correspond.To analyze volumes of diffuse low-grade gliomas (LGGs) based on preoperative 3-D FLAIR MRIs compared to intraoperative 3-D US image recordings to quantitatively assess potential discrepancies between the 2 imaging modalities.Twenty-three patients with supratentorial WHO grade II gliomas undergoing primary surgery guided by neuronavigation based on preoperative FLAIR MRI and navigated 3-D US were included. Manual volume segmentation was performed twice in 3-D Slicer version 4.0.0 to assess intrarater variabilities and compare modalities with regard to tumor volume. Factors possibly related to correspondence between MRI and US were also explored.In 20 out of 23 patients (87%), the LGG tumor volume segmented from intraoperative US data was smaller than the tumor volume segmented from the preoperative 3-D FLAIR MRI. The median difference between MRI and US volumes was 7.4 mL (range: -4.9-58.7 mL, P.001) with US LGG volumes corresponding to a median of 74% (range: 42%-183%) of the MRI LGG volumes. However, there was considerable intraobserver variability for US volumes. The correspondence between MRI and US data was higher for astrocytomas (92%).The tumor volumes of LGGs segmented from intraoperative US images were most often smaller than the tumor volumes segmented from preoperative MRIs. There was a much better match between the 2 modalities in astrocytomas.

Assessment of size and growth are key radiological factors in low-grade gliomas (LGGs), both for prognostication and treatment evaluation, but the reliability of LGG-segmentation is scarcely studied. With a diffuse and invasive growth pattern, usually without contrast enhancement, these tumors can be difficult to delineate. The aim of this study was to investigate the intra-observer variability in LGG-segmentation for a radiologist without prior segmentation experience. Pre-operative 3D FLAIR images of 23 LGGs were segmented three times in the software 3D Slicer. Tumor volumes were calculated, together with the absolute and relative difference between the segmentations. To quantify the intra-rater variability, we used the Jaccard coefficient comparing both two (J2) and three (J3) segmentations as well as the Hausdorff Distance (HD). The variability measured with J2 improved significantly between the two last segmentations compared to the two first, going from 0.87 to 0.90 (p = 0.04). Between the last two segmentations, larger tumors showed a tendency towards smaller relative volume difference (p = 0.07), while tumors with well-defined borders had significantly less variability measured with both J2 (p = 0.04) and HD (p

Background:Individuals with traumatic brain injury (TBI) often suffer from a number of enduring cognitive impairments such as in attention, memory, speed of processing information and dual-task performance.Objective:The aim of this study was to assess the patterns of regional brain activation in response to the Tower of London (ToL) task in a group of patients suffering from chronic TBI using functional magnetic resonance imaging (fMRI).Methods:fMRI was performed during performance of the ToL planning task in 10 patients suffering from severe TBI and in 10 age- and sex-matched controls using a 3 T magnetic resonance scanner.Results:Performance data showed no difference in response accuracy between the TBI group and the healthy control group. Statistical parametric brain maps showed that the TBI group activates larger and additional areas of the cerebral cortex than the healthy control group both for tasks and for a subtraction contrast between the tasks.Conclusions:The results of this study are interpreted as a cortical reorganization inside the executive system of vigilance and working memory in patients with TBI. Both parietal and frontal areas are recruited to compensate for damaged brain tissue.

The hemodynamic response (HDR) function is the basis for standard functional magnetic resonance imaging (fMRI) analysis. HDR is influenced by white matter inflammation. Traumatic brain injury (TBI) is frequently accompanied by diffuse white matter injury, but the effect of this on the HDR has not been investigated. The aims of the present study were to describe the HDR in visual cortex and examine its relationship with the microstructure of the optic radiation in severe TBI survivors and controls. Ten severe TBI survivors without visual impairments, but with known diffuse axonal injury, and 9 matched controls underwent diffusion tensor imaging (DTI) and fMRI. From the fMRI time series obtained during brief randomized visual stimuli, blood oxygenation level-dependent (BOLD) signal changes for each subject were estimated in V1, and group HDR curves were produced. Standard between-group analysis of BOLD activation in V1 + V2 was performed. For each individual the optic radiations were identified and fractional anisotropy (FA) plus mean apparent diffusion coefficient (ADC(mean)) values for these tracts were calculated. Group HDR curves from the visual cortex were fully transposable between TBI survivors and controls, despite a significant reduction in FA in the optic radiation in TBI survivors. A significant correlation between BOLD signal in the visual cortex and FA values in the optical tract was present in controls, but not in TBI survivors. Between-group comparisons showed that TBI survivors had increased areas of activation in V1 and V2. The HDR appears to be intact in traumatic white matter damage, supporting the validity of using standard fMRI methodology to study neuroplasticity in TBI.

Background Structural magnetic resonance imaging (MRI) and histopathologic tissue sampling are routinely performed as part of the diagnostic workup for patients with glioma. Because of the heterogeneous nature of gliomas, there is a risk of undergrading caused by histopathologic sampling errors. MRI has limitations in identifying tumor grade and type, detecting diffuse invasive growth, and separating recurrences from treatment induced changes. Positron emission tomography (PET) can provide quantitative information of cellular activity and metabolism, and may therefore complement MRI. In this report, we present the first patient with brain glioma examined with simultaneous PET/MRI using the amino acid tracer 18F-fluciclovine (18F-FACBC) for intraoperative image-guided surgery. Case Description A previously healthy 60-year old woman was admitted to the emergency care with speech difficulties and a mild left-sided hemiparesis. MRI revealed a tumor that was suggestive of glioma. Before surgery, the patient underwent a simultaneous PET/MRI examination. Fused PET/MRI, T1, FLAIR, and intraoperative three-dimensional ultrasound images were used to guide histopathologic tissue sampling and surgical resection. Navigated, image-guided histopathologic samples were compared with PET/MRI image data to assess the additional value of the PET acquisition. Histopathologic analysis showed anaplastic oligodendroglioma in the most malignant parts of the tumor, while several regions were World Health Organization (WHO) grade II. Conclusions 18F-Fluciclovine uptake was found in parts of the tumor where regional WHO grade, cell proliferation, and cell densities were highest. This finding suggests that PET/MRI with this tracer could be used to improve accuracy in histopathologic tissue sampling and grading, and possibly for guiding treatments targeting the most malignant part of extensive and eloquent gliomas. © 2017 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

High-grade gliomas are the most common primary brain tumour. Glioblastomas (World Health Organization Grade IV) and anaplastic astrocytomas (World Health Organization Grade III) account for 70-85% of high-grade gliomas. High-grade gliomas are associated with high morbidity and mortality. Virtually all patients with high-grade glioma will experience recurrence and will eventually die from progressing disease. Despite surgery, radiotherapy, and chemotherapy, median survival in patients with glioblastoma still does not exceed 12 months. The median survival for patients with anaplastic astrocytoma (AA) has been reported to be between 2 and 3 years. According to current guidelines, surgery is warranted to establish a histopathologic diagnosis and to achieve safe, maximal, and feasible resection. However, these aggressive tumours cannot be cured and overly aggressive resection is not recommended due to the risk of new neurological deficits. High-grade glioma surgery is a delicate balance between achieving maximal tumour resection and inducing new deficits.In our department a neuronavigation system based on preoperative 3D magnetic resonance imaging (MRI) and intraoperative 3D ultrasound is utilised when resecting high-grade gliomas. Blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) and diffusion tensor tractography (DTT) are specialized MRI techniques for imaging eloquent cortices and neural tracts in grey and white matter, respectively. The neuronavigation system allows the integration of BOLD fMRI and DTT data if the tumours are located in eloquent regions.In the two first studies of this thesis we sought to investigate the use of BOLD fMRI and DTT for preoperative assessments and determine whether using these data together with 3D intraoperative ultrasound enabled safe resection of high-grade gliomas situated in eloquent regions. In the third study we wanted to explore the impact of surgical morbidity on functional outcome and survival in GBM patients. Further, we sought to determine extent of tumour resection achieved in a consecutive sample of primary GBM from our own department. In the fourth study we wanted to determine if changes in health related quality of life early after surgery could be a predictor for survival in patients with glioblastoma. The aims of the fifth study were to explore survival and the treatment provided to elderly patients (≥66 years) diagnosed with glioblastoma during a 20-year time period in a population-based cohort using the Norwegian Cancer Registry.This thesis investigated the role of surgical resection in the treatment of high-grade gliomas and the following conclusions can be drawn:- The combination of BOLD fMRI, DTT, and 3D intraoperative ultrasound may facilitate resection of high-grade gliomas harboured in eloquent areas while preserving motor and language function.- Functional neuronavigation combined with intraoperative 3D ultrasound can, in most patients, enable resection of brain lesions with general anaesthesia without jeopardizing neurological function.- Patients with perioperative complications and surgically acquired deficits were less likely to receive adjuvant therapy.- Early deterioration in HRQL after surgery was independently and markedly associated with impaired survival in patients with glioblastoma.- Advancing age remains a very strong and independent negative prognostic factor in glioblastoma. Although there has been an increase in the aggressiveness of treatment provided to elderly with glioblastoma, the gain for the oldest age group seems at best very modest. The prognosis of the oldest age group remains very poor, despite multimodal treatment.

The aim of this study was to establish a robust set of motor tasks that could be used to functionally delineate the motor cortex with blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI) at 3 T and produce precise functional maps for pre-operative planning and functional neuronavigation.Twelve male and four female control subjects were recruited for this study which examined six different motor tasks. Finger-, tongue-, lip- and toe-movements, as well as isometric upper arm- and thigh-contraction tasks were conducted during separate scans on a 3 T MRI scanner. Furthermore, patients that previously had undergone similar motor tasks were reviewed, to evaluate whether this set of tasks was able to be adopted for use in a population of patients with brain lesions.The results of this study indicated that the finger-, toe- and tongue-motor tasks were the most robust in identifying their respective primary motor area. Moreover, all three tasks activated regions at regular intervals along the convexity of the hemisphere, making it possible to functionally delineate the primary motor cortex in both healthy subjects and patients.The motor tasks described in this study (toe, finger and tongue) were effective at localizing the primary motor cortex for the purposes of neurosurgical planning. These three tasks produced the highest success rate and resulted in activations at regular intervals along the convexity of the hemisphere, allowing the delineation of the entire motor strip even in the presence of edema and anatomical distortions.

Objective: This case report suggests that screening of patients with psychiatric symptoms using modern neuroimaging can help identify organic causes of mental illness. Method: A single case study was reported. Results: We report the case of a 25-year-old woman with a recent diagnosis of bipolar II disorder having an magnetic resonance imaging (MRI) scan as part of a research project that reveals an intraventricular brain tumour. The latter is most likely the cause of her irritability and ‘hypomanic’ symptoms and is defined anatomically using diffusion tensor imaging and structural and functional imaging using MRI and positron emission tomography. Conclusion: The lesion in this individual case most probably produces mood symptoms by impinging upon the fornix, a component of the limbic system. However, more generally, the increase in diagnosis of bipolar disorder has to be tempered against alternate causes of similar symptoms and necessitates vigilance of potential organic mechanisms.

Objective. The aims of this study were: 1) To develop protocols for, integration and assessment of the usefulness of high quality fMRI (functional magnetic resonance imaging) and DTI (diffusion tensor imaging) data in an ultrasound-based neuronavigation system. 2) To develop and demonstrate a co-registration method for automatic brain-shift correction of pre-operative MR data using intra-operative 3D ultrasound. Methods. Twelve patients undergoing brain surgery were scanned to obtain structural and fMRI data before the operation. In six of these patients, DTI data was also obtained. The preoperative data was imported into a commercial ultrasound-based navigation system and used for surgical planning and guidance. Intra-operative ultrasound volumes were acquired when needed during surgery and the multimodal data was used for guidance and resection control. The use of the available image information during planning and surgery was recorded. An automatic voxel-based registration method between preoperative MRA and intra-operative 3D ultrasound angiography (Power Doppler) was developed and tested postoperatively. Results. The study showed that it is possible to implement robust, high-quality protocols for fMRI and DTI and that the acquired data could be seamlessly integrated in an ultrasound-based neuronavigation system. Navigation based on fMRI data was found to be important for pre-operative planning in all twelve procedures. In five out of eleven cases the data was also found useful during the resection. DTI data was found to be useful for planning in all five cases where these data were imported into the navigation system. In two out of four cases DTI data was also considered important during the resection (in one case DTI data were acquired but not imported and in another case fMRI and DTI data could only be used for planning). Information regarding the location of important functional areas (fMRI) was more beneficial during the planning phase while DTI data was more helpful during the resection. Furthermore, the surgeon found it more user-friendly and efficient to interpret fMRI and DTI information when shown in a navigation system as compared to the traditional display on a light board or monitor. Updating MRI data for brain-shift using automatic co-registration of preoperative MRI with intra-operative ultrasound was feasible. Conclusion. In the present study we have demonstrated how both fMRI and DTI data can be acquired and integrated into a neuronavigation system for improved surgical planning and guidance. The surgeons reported that the integration of fMRI and DTI data in the navigation system represented valuable additional information presented in a user-friendly way and functional neuronavigation is now in routine use at our hospital. Furthermore, the present study showed that automatic ultrasound-based updates of important pre-operative MRI data are feasible and hence can be used to compensate for brain shift.

Blood-Oxygenation-Level-Dependent functional Magnetic-Resonance-Imaging (BOLD fMRI) and Diffusion Tensor Imaging (DTI) are specialized MRI-techniques for imaging of eloquent cortices and neural tracts in gray and white matter, respectively. By processing of the BOLD fMRI images, it is possible to map eloquent cortices and visualize them as statistical parametric color coded maps to be overlain on for instance anatomical MRI-images. Processing of the DTI images using a technique called Diffusion Tensor Tractography (DTT), makes it possible to map important neural tracts and visualize them as fiber bundles. The results from these examinations may be helpful during planning and resection of brain lesions, by providing information on functional eloquent cortices and important white matter tracts in close proximity to the lesion, as the goal of surgery is to maximize resection without inflicting new neurological deficits. This functional information may also be incorporated into neuronavigation systems and utilized during surgery. The overall aim of this thesis was to develop, implement, and evaluate BOLD fMRI and DTT at 3 Tesla for routine use in preoperative planning and 3D ultrasound-guided functional neuronavigation combined with minimal invasive neurosurgery. Obtaining normative functional data in healthy subjects is a first step in the development of clinical useful tasks. Thus, we investigated different motor tasks in a group of healthy subjects to evaluate which combination was best suited for functional mapping and delineation of the primary motor cortex. Movement of fingers, toes, and tongue yielded the highest success rates in healthy subjects and proved equally successful in patients with brain lesions. We also investigated a set of language tasks and the reproducibility of the activation size and location for these. We found that a word-generation task and a responsive naming task should be preferred for mapping of the frontal and temporal language area, respectively. A novel language task with the potential to map both the frontal and temporal language areas was also established. This task has the advantage of being more engaging, which may help the subjects to maintain concentration and stay motivated throughout the scanning session. We have also evaluated the use of BOLD fMRI and DTT in 3D ultrasound-guided functional neuronavigation by retrospectively reviewing patients operated during a threeyear period. We found that surgery gave an overall significant improvement in clinical status compared to preoperatively, and for gliomas we found a median residual tumor volume of 11%. We also found a significant correlation between decreasing lesion-toeloquent- area distance and increasing residual tumor percentage in gliomas, indicating that the resections were performed as a compromise between removing as much tumor tissue as possible without jeopardizing eloquent areas. Furthermore, some glioma patients with lesion-to-eloquent-area distance less than 2 mm also had radical resections without post-operative neurological deficits. Thus indicating that guided functional neuronavigation with updated anatomical information using 3D ultrasound gives the surgeon an advantage when resecting brain lesions, as well as facilitates maximal tumor resection with minimal deficit. The challenges ahead lie in establishing standardized tasks and analysis for processing of these investigations, as well as carrying out prospective outcome studies or clinical randomized trials in order to produce evidence for effect of presurgical BOLD fMRI and DTT on morbidity and mortality in patients with brain lesions.

Background: Acquired deficits following glioma resection may not only occur due to accidental resection of normal brain tissue. The possible importance of ischemic injuries in causing neurological deficits after brain tumor surgery is not much studied. We aimed to study the volume and frequency of early postoperative circulatory changes (i.e. infarctions) detected by diffusion weighted resonance imaging (DWI) in patients with surgically acquired neurological deficits compared to controls. Methods: We designed a 1∶1 matched case-control study in patients with diffuse gliomas (WHO grade II–IV) operated with 3D ultrasound guided resection. 42 consecutive patients with acquired postoperative dysphasia and/or new motor deficits were compared to 42 matched controls without acquired deficits. Controls were matched with respect to histopathology, preoperative tumor volumes, and eloquence of location. Two independent radiologists blinded for clinical status assessed the postoperative DWI findings. Results: Postoperative peri-tumoral infarctions were more often seen in patients with acquired deficits (63% versus 41%, p = 0.046) and volumes of DWI abnormalities were larger in cases than in controls with median 1.08 cm3 (IQR 0–2.39) versus median 0 cm3 (IQR 0–1.67), p = 0.047. Inter-rater agreement was substantial (67/82, κ = 0.64, p