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This study aimed whether the uptake of amino tracer positron emission tomography (PET) can be used as an additional imaging biomarker to estimate the prognosis of glioma. Participants comprised 56 adult patients with newly diagnosed and untreated World Health Organization (WHO) grade II–IV astrocytic glioma who underwent surgical excision and were evaluated by 11C-methionine PET prior to the surgical excision at Osaka City University Hospital from July 2011 to March 2018. Clinical and imaging studies were retrospectively reviewed based on medical records at our institution. Preoperative Karnofsky Performance Status (KPS) only influenced progression-free survival (hazard ratio [HR] 0.20; 95% confidence interval [CI] 0.10–0.41, p  < 0.0001), whereas histology (anaplastic astrocytoma: HR 5.30, 95% CI 1.23–22.8, p  = 0.025; glioblastoma: HR 11.52, 95% CI 2.27–58.47, p  = 0.0032), preoperative KPS ≥ 80 (HR 0.23, 95% CI 0.09–0.62, p  = 0.004), maximum lesion-to-contralateral normal brain tissue (LN max) ≥ 4.03 (HR 0.24, 95% CI 0.08–0.71, p  = 0.01), and isocitrate dehydrogenase (IDH) status (HR 14.06, 95% CI 1.81–109.2, p  = 0.011) were factors influencing overall survival (OS) in multivariate Cox regression. OS was shorter in patients with LN max ≥ 4.03 (29.3 months) than in patients with LN max < 4.03 (not reached; p  = 0.03). OS differed significantly between patients with IDH mutant/LN max < 4.03 and patients with IDH mutant/LN max ≥ 4.03. LN max using 11C-methionine PET may be used in prognostic markers for newly identified and untreated WHO grade II–IV astrocytic glioma.

Identification of genotypes is crucial for treatment of glioma. Here, we developed a method to predict tumor genotypes using a pretrained convolutional neural network (CNN) from magnetic resonance (MR) images and compared the accuracy to that of a diagnosis based on conventional radiomic features and patient age. Multisite preoperative MR images of 164 patients with grade II/III glioma were grouped by IDH and TERT promoter (pTERT) mutations as follows: (1) IDH wild type, (2) IDH and pTERT co-mutations, (3) IDH mutant and pTERT wild type. We applied a CNN (AlexNet) to four types of MR sequence and obtained the CNN texture features to classify the groups with a linear support vector machine. The classification was also performed using conventional radiomic features and/or patient age. Using all features, we succeeded in classifying patients with an accuracy of 63.1%, which was significantly higher than the accuracy obtained from using either the radiomic features or patient age alone. In particular, prediction of the pTERT mutation was significantly improved by the CNN texture features. In conclusion, the pretrained CNN texture features capture the information of IDH and TERT genotypes in grade II/III gliomas better than the conventional radiomic features.

Molecular biological characterization of tumors has become a pivotal procedure for glioma patient care. The aim of this study is to build conventional MRI-based radiomics model to predict genetic alterations within grade II/III gliomas attempting to implement lesion location information in the model to improve diagnostic accuracy. One-hundred and ninety-nine grade II/III gliomas patients were enrolled. Three molecular subtypes were identified: IDH1/2 -mutant, IDH1/2 -mutant with TERT promoter mutation, and IDH- wild type. A total of 109 radiomics features from 169 MRI datasets and location information from 199 datasets were extracted. Prediction modeling for genetic alteration was trained via LASSO regression for 111 datasets and validated by the remaining 58 datasets. IDH mutation was detected with an accuracy of 0.82 for the training set and 0.83 for the validation set without lesion location information. Diagnostic accuracy improved to 0.85 for the training set and 0.87 for the validation set when lesion location information was implemented. Diagnostic accuracy for predicting 3 molecular subtypes of grade II/III gliomas was 0.74 for the training set and 0.56 for the validation set with lesion location information implemented. Conventional MRI-based radiomics is one of the most promising strategies that may lead to a non-invasive diagnostic technique for molecular characterization of grade II/III gliomas.

Introduction Although cavernous sinus (CS) dural arteriovenous fistulas (d-AVFs) are usually treated with transvenous embolization (TVE) via the inferior petrosal sinus (IPS), IPSs are sometimes thrombosed and angiographically invisible. In such cases, the first obstacle to TVE is detecting the entry to the IPS. We report a new technique for TVE via IPS using intravascular ultrasonography (IVUS). Methods Three consecutive cases of CS d-AVF with ipsilateral or bilateral IPS occlusion were involved in this study. On TVE, the orifice of the IPS was investigated with IVUS placed in the jugular vein or jugular bulb. Results This technique has been successfully adapted in all three cases. In two of these cases, IPS was well visualized with the help of IVUS, and TVE was successfully performed. Conclusion To our knowledge, this is the first report to mention the usefulness of IVUS for detecting angiographically occult IPS.

Background The venous drainage of the temporal lobe, through bridging veins to the middle cranial fossa, is pivotal in determining the surgical corridor for skull base lesions. In dealing with select cases, where venous drainage was an obstacle in the surgical approach, we hypothesized that staged ‘intentional’ ligation of the dominant pathway of venous drainage would provide a safer and wider access to skull base tumors. We study the indications and safety of this surgical strategy in the management of skull base lesions. Materials and methods From 1995 to 2012, 318 patients with skull base tumors were treated at our institute by the fronto-orbito-zygomatic (FOZ) or transpetrosal approaches, eight of whom we planned for staged ‘intentional’ bridging vein ligation. Seven patients underwent planned ligation of the bridging veins from the temporal lobe to the middle cranial fossa floor in the first stage, followed by definitive surgery through the desired skull base approach, in the second stage, while in one patient the strategy was abandoned. These patients were evaluated with respect to their clinical presentation, pre- and post-operative radiology including venogram, intra-operative findings and post-operative course. Results Seven patients, four males and three females, with ages ranging from 16 to 63 years, underwent staged ‘intentional’ bridging vein ligation. The diagnoses were recurrent craniopharyngioma in four, and petroclival meningioma, sphenopetroclival meningioma and spheno-orbital meningioma in one each. Six of these lesions were approached from the dominant (left) side, while one lesion was on the right side. Venograms done after the first-stage procedure showed obliteration of the dominant venous drainage with opening up of anastomotic venous channels in all patients. All patients tolerated the first-stage procedure well; only one patient showed asymptomatic mild temporal lobe edema on MRI, which resolved in 3 weeks. None of the patients had venous complications after definitive surgery. One patient with recurrent chordoma, who was planned for staged ligation, did not undergo ligation as, intra-operatively, the draining channel turned out to be a cortical vein, which could be mobilized without ligation. Conclusion In an attempt to detether the temporal lobe, the disconnection of the bridging veins from the temporal lobe to the middle cranial fossa floor in the first stage may lead to re-direction of the venous outflow over time. This may allow skull base surgeons a better surgical corridor and ensure safety of venous structures during the definitive surgery.

Objective(s): 18F-fluciclovine (trans-1-amino-3-[18F] fluorocyclobutanecarboxylic acid, [FACBC]) is an artificial amino acid radiotracer used for positron emission tomography (PET) studies, which is metabolically stable in vivo and has a long half-life. It has already been shown that FACBC-PET is useful for glioma imaging. However, there have been no reports evaluating the efficiency of FACBC-PET in the diagnosis of brain tumors in comparison with other PET tracers in clinical studies. The purpose of this study was to investigate the efficacy of FACBC-PET imaging in glioma diagnosis, compared to L-methyl-11C-methionine (MET)-PET. Methods: Six consecutive patients (four male, two female), who were clinically suspected of having high- or low-grade glioma, received both FACBC-PET and MET-PET within a two-week interval. T1-weighted, contrast-enhanced, T1-weighted, and fluid-attenuated inversion recovery magnetic resonance imaging was performed to assist with subsequent tissue resection. Visual findings and semi-quantitative analyses of FACBC and MET uptake, using standardized uptake values (SUVs) and lesion-to-contralateral normal brain tissue (LN) ratios, were evaluated to compare PET images. Results: SUVs for FACBC were lower than those for MET in the non-lesion cerebral cortex, brain stem, and cerebellar hemisphere. There was a weak positive correlation between FACBC and MET uptake in glioma tissue, although L/N ratios for FACBC were higher than those for MET in all the cases. Conclusion: FACBC-PET showed higher contrast than MET-PET by both visual and semi-quantitative analyses and may therefore provide better assessment for the detection of glioma. This study was registered as clinical trial (No. JapicCTI-132289).

The aim of this study was to determine the uptake of L-[methyl-(11)C]-methionine ((11)C-MET) in the normal brain of patients younger than 20 y, to facilitate more accurate diagnoses in young patients. Eighty-two patients were categorized into 4 groups according to their age. They underwent (11)C-MET PET, and a standardized uptake value (SUV) was determined for different brain regions including the frontal lobe, parietal lobe, cerebellum, and brain stem. Compared with all other parts of the brain, the cerebellum had the highest SUV. A tendency for a positive relationship between SUV and age was found in all regions, and a significant relationship with SUV was found in the frontal lobe and cerebellum. The character of SUV in the normal brains of children is different from that of adults, and these normal SUV data will play an important role as a critical reference value.

To investigate clinicopathological significance of autophagy and its association with genetic alterations in gliomas. The expression of three autophagy-related proteins, light chain-3 (LC3), beclin 1, and p62 was immunohistochemically analyzed in 32 low-grade gliomas and 65 high-grade gliomas. LC3, beclin 1, and p62 expression was positive in 70/94 (74%), 51/94 (54%) and 55/96 (57%) gliomas, respectively. High expression of LC3, beclin 1 and p62 was significantly more frequent in high-grade gliomas than in low-grade. Positive expression of LC3, beclin 1 and p62 were significantly positively correlated with overall survival, methylation of O -methylyguanine-DNA methyltransferase (MGMT) promoter, mutations of isocitrate dehydrogenase 1 (IDH1) and telomerase reverse transcriptase (TERT) promoter, and 1p/19q co-deletion. Kaplan-Meier analyses revealed that LC3, p62 and autophagy status (positivity for at least two of the three proteins) were significantly associated with poorer survival. Autophagy might be associated with the progression of glioma, particularly high-grade, and thus might be a useful prognostic factor in patients with glioma.

To image cerebral neural activity in ischemic areas, we proposed a novel technique to analyze spontaneous neuromagnetic fields based on standardized low-resolution brain electromagnetic tomography modified for a quantifiable method (sLORETA-qm). Using a 160-channel whole-head-type magnetoencephalographic system, cerebral magnetic fields were obtained pre- and postoperatively from 5 patients with unilateral internal carotid artery occlusive disease and 16 age-matched healthy volunteers. For quantitative imaging, voxel-based time-averaged intensities of slow waves in 4 frequency bands (0.3–2 Hz, 2–4 Hz, 4–6 Hz and 6–8 Hz) were obtained by the proposed technique based on sLORETA-qm. Positron emission tomography with 15O gas inhalation (15O-PET) was also performed in these patients to evaluate cerebral blood flow and metabolism. In all 5 patients, slow waves in every frequency band were distributed in the area of cerebrovascular insufficiency, as confirmed by 15O-PET preoperatively. In 4 patients, slow-wave intensities in theta bands (4–6 Hz, 6–8 Hz) decreased postoperatively along with improvements in cerebral blood flow and metabolism, whereas delta bands (0.3–2 Hz, 2–4 Hz) showed no significant differences between pre- and postoperatively. One patient with deterioration of cerebral infarction after surgery showed marked increases in slow-wave intensities in delta bands (0.3–2 Hz, 2–4 Hz) postoperatively, with distribution close to the infarct region. The proposed quantitative imaging of spontaneous neuromagnetic fields enabled clear visualization and alternations of cerebral neural conditions in the ischemic area. This technique may offer a novel, non-invasive method for identifying cerebral ischemia, although further studies in a larger number of patients are warranted.

Glioblastoma (GBM) is one of the most lethal solid cancers due to its highly invasive nature. The malignant potential of GBM cells might be partially regulated by surrounding normal cells, such as oligodendrocytes or fibroblasts. The aim of this study was to examine the interaction between stromal cells and GBM cells. Two GBM cell lines were used. The effect of stromal cells, oligodendrocytes or fibroblasts, on the invasive ability of GBM cells was examined by wound-healing assay and invasion assay. Oligodendrocytes, in contrast to fibroblasts, significantly increased the migration and invasive ability of GBM cells. Angiopoietin-2 levels were high in the conditioned medium obtained from oligodendrocytes. Angiopoietin-2 significantly increased the motility of GBM, and the motility-stimulating activity of the oligodendrocytes-derived conditioned medium was significantly decreased by anti-angiopoietin-2-neutralizing antibody. Glioma stromal cells, oligodendrocytes, might up-regulate the invasiveness of GBM cells via angiopoietin-2 signaling.