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Cluster of differentiation (CD) 166 or activated leukocyte cell adhesion molecule (ALCAM) is a transmembrane molecule known to be an intercellular adhesion factor. The expression and function of ALCAM in medulloblastoma (MB), a pediatric brain tumor with highly advanced molecular genetics, remains unclear. Therefore, this study aimed to clarify the significance and functional role of ALCAM expression in MB. ALCAM expression in 45 patients with MB was evaluated by immunohistochemical analysis of formalin-fixed paraffin-embedded clinical specimens and the relationship between ALCAM expression and pathological type/molecular subgroup, such as WNT, SHH, Group 3, and Group 4, was examined. Eight ALCAM positive (18%), seven partially positive (16%), and 30 negative (67%) cases were detected. All seven cases of the WNT molecular subgroup were ALCAM positive and ALCAM expression strongly correlated with this subgroup (P < 0.0001). In addition, functional studies using MB cell lines revealed ALCAM expression affected proliferation and migration as a positive regulator in vitro. However, ALCAM silencing did not affect survival or the formation of leptomeningeal dissemination in an orthotopic mouse model, but did induce a malignant phenotype with increased tumor cell invasion at the dissemination sites (P = 0.0029). In conclusion, our results revealed that ALCAM exhibited highly specific expression in the WNT subgroup of MB. Furthermore, we demonstrated that the cell kinetics of MB cell lines can be altered by the expression of ALCAM. [ABSTRACT FROM AUTHOR]

Brain Tumor Image Analysis (BraTumIA) is a fully automated segmentation tool dedicated to detecting brain tumors imaged by magnetic resonance imaging (MRI). BraTumIA has recently been applied to several clinical investigations; however, the validity of this novel method has not yet been fully examined. The present study was conducted to validate the quality of tumor segmentation with BraTumIA in comparison with results from 11C-methionine positron emission tomography (MET-PET). A total of 45 consecutive newly diagnosed high-grade gliomas imaged by MRI and MET-PET were analyzed. Automatic tumor segmentation was conducted by BraTumIA and the resulting segmentation images were registered to MET-PET. Three-dimensional conformal association between these two modalities was calculated, considering MET-PET as the gold standard. High underestimation and overestimation errors were observed in tumor segmentation calculated by BraTumIA compared with MET-PET. Furthermore, when the tumor/normal ratio threshold was set at 1.3 from MET-PET, the BraTumIA false-positive fraction was ~0.4 and the false-negative fraction was 0.9. By tightening this threshold to 2.0, the BraTumIA false-positive fraction was 0.6 and the false-negative fraction was 0.6. Following comparison of segmentation performance with BraTumIA with regard to glioblastoma (GBM) and World Health Organization (WHO) grade III glioma, GBM exhibited better segmentation compared with WHO grade III glioma. Although BraTumIA may be able to detect enhanced tumors, non-enhancing tumors and necrosis, the spatial concordance rate with MET-PET was relatively low. Careful interpretation is therefore required when using this technique. [ABSTRACT FROM AUTHOR]

A number of studies have revealed the usefulness of multimodal imaging in gliomas. Although the results have been heavily affected by the method used for region of interest (ROI) design, the most discriminatory method for setting the ROI remains unclear. The aim of the present study was to determine the most suitable ROI design for 18F-fluorodeoxyglucose (FDG) and 11C-methionine (MET) positron emission tomography (PET), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) obtained by diffusion tensor imaging (DTI) from the viewpoint of grades of non-enhancing gliomas. A total of 31 consecutive patients with newly diagnosed, histologically confirmed magnetic resonance (MR) non-enhancing gliomas who underwent FDG-PET, MET-PET and DTI were retrospectively investigated. Quantitative measurements were performed using four different ROIs; hotspot/tumor center and whole tumor, constructed in either two-dimensional (2D) or three-dimensional (3D). Histopathological grading of the tumor was considered as empirical truth and the quantitative measurements obtained from each ROI was correlated with the grade of the tumor. The most discriminating ROI for non-enhancing glioma grading was different according to the different imaging modalities. 2D-hotspot/center ROI was most discriminating for FDG-PET (P=0.087), ADC map (P=0.0083), and FA map (P=0.25), whereas 3D-whole tumor ROI was best for MET-PET (P=0.0050). In the majority of scenarios, 2D-ROIs performed better than 3D-ROIs. Results from the image analysis using FDG-PET, MET-PET, ADC and FA may be affected by ROI design and the most discriminating ROI for non-enhancing glioma grading was different according to the imaging modality. [ABSTRACT FROM AUTHOR]

Reports have suggested that tumor textures presented on T2-weighted images correlate with the genetic status of glioma. Therefore, development of an image analyzing framework that is capable of objective and high throughput image texture analysis for large scale image data collection is needed. The current study aimed to address the development of such a framework by introducing two novel parameters for image textures on T2-weighted images, i.e., Shannon entropy and Prewitt filtering. Twenty-two WHO grade 2 and 28 grade 3 glioma patients were collected whose pre-surgical MRI and IDH1 mutation status were available. Heterogeneous lesions showed statistically higher Shannon entropy than homogenous lesions (p = 0.006) and ROC curve analysis proved that Shannon entropy on T2WI was a reliable indicator for discrimination of homogenous and heterogeneous lesions (p = 0.015, AUC = 0.73). Lesions with well-defined borders exhibited statistically higher Edge mean and Edge median values using Prewitt filtering than those with vague lesion borders (p = 0.0003 and p = 0.0005 respectively). ROC curve analysis also proved that both Edge mean and median values were promising indicators for discrimination of lesions with vague and well defined borders and both Edge mean and median values performed in a comparable manner (p = 0.0002, AUC = 0.81 and p < 0.0001, AUC = 0.83, respectively). Finally, IDH1 wild type gliomas showed statistically lower Shannon entropy on T2WI than IDH1 mutated gliomas (p = 0.007) but no difference was observed between IDH1 wild type and mutated gliomas in Edge median values using Prewitt filtering. The current study introduced two image metrics that reflect lesion texture described on T2WI. These two metrics were validated by readings of a neuro-radiologist who was blinded to the results. This observation will facilitate further use of this technique in future large scale image analysis of glioma. [ABSTRACT FROM AUTHOR]

Rathke’s cleft cyst (RCC) apoplexy is a rare clinical entity. We report a case of apoplexy of an RCC followed by cerebral infarction. A 67-year-old woman was found lying on the street unconscious. She had fallen from her motorbike. On referral to our hospital she gradually regained consciousness and presented with no neurological deficits. CT showed a round and slightly hyperdense area in the suprasellar region. However, the attending physician did not find this abnormal finding on CT and the patient was discharged the same day. Thirteen days after the first emergency visit she developed left hemiparesis and dysarthria. CT showed a round hypodense area in the suprasellar region. The change of the density in the suprasellar region on CT suggested the pituitary apoplexy. CT also showed a low density area in the territory of the right middle cerebral artery, which indicated the cerebral infarction. MR angiography revealed poor visibility and stenotic changes of right middle cerebral arteries. Transsphenoidal surgery was performed. Histopathological findings confirmed a hemorrhagic RCC. Postoperative MR angiography showed that the visibility and stenosis of right middle cerebral arteries were recovered. This is the rare case of apoplexy of an RCC followed by cerebral infarction. [ABSTRACT FROM AUTHOR]

The diagnosis and prognostication of glioblastoma (GBM) remain to be solely dependent on histopathological findings and few molecular markers, despite the clinical heterogeneity in this entity. To address this issue, we investigated the prognostic impact of copy number alterations (CNAs) using two population-based IDH-wild-type GBM cohorts: an original Japanese cohort and a dataset from The Cancer Genome Atlas (TCGA). The molecular disproportions between these cohorts were dissected in light of cohort differences in GBM. The Japanese cohort was collected from cases registered in Kansai Molecular Diagnosis Network for CNS tumors (KNBTG). The somatic landscape around CNAs was analyzed for 212 KNBTG cases and 359 TCGA cases. Next, the clinical impacts of CNA profiles were investigated for 140 KNBTG cases and 152 TCGA cases treated by standard adjuvant therapy using temozolomide-based chemoradiation. The comparative profiling indicated unequal distribution of specific CNAs such as EGFR, CDKN2A, and PTEN among the two cohorts. Especially, the triple overlap CNAs in these loci (triple CNA) were much higher in frequency in TCGA (70.5%) than KNBTG (24.3%), and its prognostic impact was independently validated in both cohorts. The KNBTG cohort significantly showed better prognosis than the TCGA cohort (median overall survival 19.3 vs 15.6 months). This survival difference between the two cohorts completely resolved after subclassifying all cases according to the triple CNA status. The prognostic significance of triple CNA was identified in IDH-wild-type GBM. Distribution difference in prognostic CNA profiles potentially could cause survival differences across cohorts in clinical studies. [ABSTRACT FROM AUTHOR]

Background. The pathophysiology of traumatic brain swelling remains little understood. An improved understanding of intracranial circulatory process related to brain herniation may have treatment implications. Objective. To investigate the cerebral hemodynamic changes associated with brain herniation syndrome due to traumatic brain swelling. Methods. Nineteen head-injured patients with evidence of refractory intracranial hypertension and transtentorial herniation were prospectively studied. Cerebral hemodynamic assessment by transcranial Doppler (TCD) ultrasonography was performed prior to decompressive craniectomy. Patients and their cerebral hemispheres were classified according to TCD-hemodynamic patterns, and the data correlated with neurological status, midline shift on CT scan, and Glasgow outcome scale scores at 6 months after injury. Results. A wide variety of cerebral hemodynamic findings were observed. Ten patients (52.7%) presented with cerebral oligoemia, 3 patients (15.8%) with cerebral hyperemia, and 6 patients with nonspecific circulatory pattern. Circulatory disturbances were more frequently found in the side of maximal cerebral swelling than in the opposite side. Pulsatility index (PI) values suggested that ICP varied from acceptable to considerably high; patients with increased PI, indicating higher microvascular resistance. No correlation was found between cerebral hemodynamic findings and outcome. Conclusions. There is a marked heterogeneity of cerebral hemodynamic disturbances among patients with brain herniation syndrome. [ABSTRACT FROM AUTHOR]