OBJECTIVE: The purpose of this study was to prospectively investigate outcome and differences in peritumoral MRI characteristics of glioblastomas (GBMs) that were in contact with the ventricles (ventricle-contacting tumors) and those that were not (noncontacting tumors). GBMs are heterogeneous tumors with variable survival. Lower survival is suggested for patients with ventricle-contacting tumors than for those with noncontacting tumors. This might be supported by aggressive peritumoral MRI features. However, differences in MRI characteristics of the peritumoral environment between ventricle-contacting and noncontacting GBMs have not yet been investigated.METHODS: Patients with newly diagnosed GBM underwent preoperative MRI with contrast-enhanced T1-weighted, FLAIR, diffusion-weighted, and perfusion-weighted sequences. Tumors were categorized into ventricle-contacting or noncontacting based on contrast enhancement. Survival analysis was performed using log-rank for univariate analysis and Cox regression for multivariate analysis. Normalized perfusion (relative cerebral blood volume [rCBV]) and diffusion (apparent diffusion coefficient [ADC]) values were calculated in 2 regions: the peritumoral nonenhancing FLAIR region overlapping the subventricular zone and the remaining peritumoral nonenhancing FLAIR region.RESULTS: Overall survival was significantly lower for patients with contacting tumors than for those with noncontacting tumors (434 vs 747 days, p < 0.001). Progression-free survival showed a comparable trend (260 vs 375 days, p = 0.094). Multivariate analysis confirmed a survival difference for both overall survival (HR 3.930, 95% CI 1.740–8.875, p = 0.001) and progression-free survival (HR 2.506, 95% CI 1.254–5.007, p = 0.009). Peritumoral perfusion was higher in contacting than in noncontacting tumors for both FLAIR regions (p = 0.04). There was no difference in peritumoral ADC values between the 2 groups.CONCLUSIONS: Patients with ventricle-contacting tumors had poorer outcomes than patients with noncontacting tumors. This disadvantage of ventricle contact might be explained by higher peritumoral perfusion leading to more aggressive behavior.

Purpose: ¹¹C-Methionine (¹¹C-MET) PET prognostication of isocitrate dehydrogenase (IDH) wild type glioblastomas is inadequate as conventional parameters such as standardized uptake value (SUV) do not adequately reflect tumor heterogeneity. We retrospectively evaluated whether volume-based parameters such as metabolic tumor volume (MTV) and total lesion methionine metabolism (TLMM) outperformed SUV for survival correlation in patients with IDH wild type glioblastomas. Methods: Thirteen IDH wild type glioblastoma patients underwent preoperative ¹¹C-MET PET. Both SUV-based parameters and volume-based parameters were calculated for each lesion. Kaplan-Meier curves with log-rank testing and Cox regression analysis were used for correlation between PET parameters and overall survival. Results: Median overall survival for the entire cohort was 393 days. MTV (HR 1.136, p = 0.007) and TLMM (HR 1.022, p = 0.030) were inversely correlated with overall survival. SUV-based ¹¹C-MET PET parameters did not show a correlation with survival. In a paired analysis with other clinical parameters including age and radiotherapy dose, MTV and TLMM were found to be independent factors. Conclusions: MTV and TLMM, and not SUV, significantly correlate with overall survival in patients with IDH wild type glioblastomas. The incorporation of volume-based ¹¹C-MET PET parameters may lead to a better outcome prediction for this heterogeneous patient population.

Background: Radiotherapy (RT) and chemotherapy are components of standard multi-modality treatment of high grade gliomas (HGG) aimed at achieving local tumor control. Treatment is neurotoxic and RT plays an important role in this, inducing damage even distant to the RT target volume. Purpose: This retrospective longitudinal study evaluated the effect of treatment on white matter and gray matter volume in the tumor-free hemisphere of HGG patients using voxel based morphometry (VBM). Method: 3D T1-weighted MR images of 12 HGG patients at multiple timepoints during standard treatment were analyzed using VBM. Segmentation of white matter and gray matter of the tumor-free hemisphere was performed. Multiple general linear models were used to asses white matter and gray matter volumetric differences between time points. A mean RT dose map was created and compared to the VBM results. Results: Diffuse loss of white matter volume, mainly throughout the frontal and parietal lobe, was found, grossly overlapping regions that received the highest RT dose. Significant loss of white matter was first noticed after three cycles of chemotherapy and persisted after the completion of standard treatment. No significant loss of white matter volume was observed between pre-RT and the first post-RT follow-up timepoint, indicating a delayed effect. Conclusion: This study demonstrated diffuse and early-delayed decreases in white matter volume of the tumor-free hemisphere in HGG patients after standard treatment. White matter volume changes occurred mainly throughout the frontal and parietal lobe and grossly overlapped with areas that received the highest RT dose.

Objectives: Radiation-induced changes (RIC) secondary to focal radiotherapy can imitate tumour progression in brain metastases and make follow-up clinical decision making unreliable. 11C-methyl-L-methionine-PET (MET-PET) is widely used for the diagnosis of RIC in brain metastases, but minimal literature exists regarding the optimum PET measuring parameter to be used. We analysed the diagnostic performance of different MET-PET measuring parameters in distinguishing between RIC and tumour progression in a retrospective cohort of brain metastasis patients. Methods: 26 patients with 31 metastatic lesions were included on the basis of having undergone a PET scan due to radiological uncertainty of disease progression. The PET images were analysed and methionine uptake quantified using standardised-uptake-values (SUV) and tumour-to-normal tissue (T/N) ratios, generated as SUVmean, SUVmax, SUVpeak, T/Nmean, T/Nmax-mean and T/Npeak-mean. Metabolic-tumour-volume and total-lesion methionine metabolism were also computed. A definitive diagnosis of either RIC or tumour progression was established by clinicoradiological follow-up of least 4 months subsequent to the investigative PET scan. Results: All MET-PET parameters except metabolic-tumour-volume showed statistically significant differences between tumour progression and lesions with RIC. Receiver-operating-characteristic curve and area-under the-curve analysis demonstrated the highest value of 0.834 for SUVmax with a corresponding optimum threshold of 3.29. This associated with sensitivity, specificity, positive predictive and negative predictive values of 70.59%, 78.57%, 80.00% and 68.75% respectively. Conclusions: MET-PET is a useful modality for the diagnosis of RIC in brain metastases. SUVmax was the PET parameter with the greatest diagnostic performance. Advances in knowledge: More robust comparisons between SUVmax and SUVpeak could enhance follow-up treatment planning.

Isocitrate dehydrogenase (IDH) mutation status is an important biomarker in the glioma-defining subtype and corresponding prognosis. This study proposes a straightforward method for 2-hydroxyglutarate (2-HG) quantification by MR spectroscopy for IDH mutation status detection and directly compares in vivo 2-HG MR spectroscopy with ex vivo 2-HG concentration measured in resected tumor tissue. Eleven patients with suspected lower-grade glioma (ten IDH1; one IDHwt) were prospectively included. Preoperatively, 3T point-resolved spectroscopy (PRESS) was acquired; 2-HG was measured as the percentage elevation of Glx3 (the sum of 2-HG and Glx) compared to Glx4. IDH mutation status was assessed by immunochemistry or direct sequencing. The ex vivo 2-HG concentration was determined in surgically obtained tissue specimens using gas chromatography–mass spectrometry. Pearson correlation was used for assessing the correlation between in vivo MR spectroscopy and ex vivo 2-HG concentration. MR spectroscopy was positive for 2-HG in eight patients, all of whom had IDH1 tumors. A strong correlation (r = 0.80, p = 0.003) between 2-HG MR spectroscopy and the ex vivo 2-HG concentration was found. This study shows in vivo 2-HG MR spectroscopy can non-invasively determine IDH status in glioma and demonstrates a strong correlation with ex vivo 2-HG concentration in patients with lower-grade glioma.

Purpose: Ventricle contact is associated with a worse prognosis and more aggressive tumor characteristics in glioblastoma (GBM). This is hypothesized to be a result of neural stem cells located around the lateral ventricles, in the subventricular zone. 11C Methionine positron emission tomography (metPET) is an indicator for increased proliferation, as it shows uptake of methionine, an amino acid needed for protein synthesis. This study is the first to study metPET characteristics of GBM in relation to ventricle contact. Methods: A total of 12 patients with IDH wild-type GBM were included. Using MRI, the following regions were determined: primary tumor (defined as contrast enhancing lesion on T1) and peritumoral edema (defined as edema visible on FLAIR excluding the enhancement). PET parameters in these areas were extracted using PET fused with MRI imaging. Parameters extracted from the PET included maximum and mean tumor-to-normal ratio (TNRmax and TNRmean) and metabolic tumor volume (MTV). Results: TNRmean of the primary tumor showed significantly higher values for the ventricle-contacting group compared to that for the non-contacting group (4.44 vs 2.67, p = 0.030). Other metPET parameters suggested higher values for the ventricle-contacting group, but these differences did not reach statistical significance. Conclusion: GBM with ventricle contact demonstrated a higher methionine uptake and might thus have increased proliferation compared with GBM without ventricle contact. This might explain survival differences and should be considered in treatment decisions.