BACKGROUND AND PURPOSE:Increased contrast enhancement has been used as a marker of malignant transformation in low-grade gliomas. This marker has been found to have limited accuracy because many low-grade gliomas with increased contrast enhancement remain grade II. We aimed to investigate whether MR spectroscopy can contribute to the diagnosis of malignant transformation in low-grade gliomas with increased contrast enhancement. MATERIALS AND METHODS:Patients with low-grade gliomas who had contemporaneous MR spectroscopy and histopathology for tumor regions with increased contrast enhancement between 2004 and 2015 were retrospectively reviewed. Clinical data collected were sex and age, Karnofsky Performance Scale, histologic subtypes, isocitrate dehydrogenase 1 mutation status, disease duration, adjuvant therapy, and post-radiation therapy duration. Imaging data collected were contrast-enhancement size, whole-tumor size, MR spectroscopy metabolite ratios, and tumor grades of regions with increased contrast enhancement. Diagnostic values of these factors on malignant transformation of low-grade gliomas were statistically analyzed. RESULTS:A total of 86 patients with 96 MR spectroscopy studies were included. Tumor grades associated with increased contrast enhancement were grade II (n = 42), grade III (n = 27), and grade IV (n = 27). On multivariate analysis, the NAA/Cho ratio was the only significant factor (P < .001; OR, 7.1; 95% CI, 3.2-16.1) diagnostic of malignant transformation. With 0.222 as the cutoff value, the sensitivity, specificity, and accuracy of NAA/Cho for diagnosing malignant transformation were 94.4%, 83.3%, and 89.6%, respectively. CONCLUSIONS:MR spectroscopy complements conventional MR imaging in the diagnosis of malignant transformation in a subgroup of low-grade gliomas with increased contrast enhancement.

Tumor-associated macrophages (TAMs) originate as circulating monocytes, and are recruited to gliomas, where they facilitate tumor growth and migration. Understanding the interaction between TAM and cancer cells may identify therapeutic targets for glioblastoma multiforme (GBM). Vascular cell adhesion molecule-1 (VCAM-1) is a cytokine-induced adhesion molecule expressed on the surface of cancer cells, which is involved in interactions with immune cells. Analysis of the glioma patient database and tissue immunohistochemistry showed that VCAM-1 expression correlated with the clinico-pathological grade of gliomas. Here, we found that VCAM-1 expression correlated positively with monocyte adhesion to GBM, and knockdown of VCAM-1 abolished the enhancement of monocyte adhesion. Importantly, upregulation of VCAM-1 is dependent on epidermal-growth-factor-receptor (EGFR) expression, and inhibition of EGFR effectively reduced VCAM-1 expression and monocyte adhesion activity. Moreover, GBM possessing higher EGFR levels (U251 cells) had higher VCAM-1 levels compared to GBMs with lower levels of EGFR (GL261 cells). Using two- and three-dimensional cultures, we found that monocyte adhesion to GBM occurs via integrin α4β1, which promotes tumor growth and invasion activity. Increased proliferation and tumor necrosis factor-α and IFN-γ levels were also observed in the adherent monocytes. Using a genetic modification approach, we demonstrated that VCAM-1 expression and monocyte adhesion were regulated by the miR-181 family, and lower levels of miR-181b correlated with high-grade glioma patients. Our results also demonstrated that miR-181b/protein phosphatase 2A-modulated SP-1 de-phosphorylation, which mediated the EGFR-dependent VCAM-1 expression and monocyte adhesion to GBM. We also found that the EGFR-dependent VCAM-1 expression is mediated by the p38/STAT3 signaling pathway. Our study suggested that VCAM-1 is a critical modulator of EGFR-dependent interaction of monocytes with GBM, which raises the possibility of developing effective and improved therapies for GBM.

BACKGROUND AND PURPOSE: Contrast leakage results in underestimation of the CBV of brain tumors. Our aim was to compare the diagnostic performance of DSC perfusion MR imaging without and with mathematic contrast-leakage correction in differentiating PCNSLs and glioblastomas. MATERIALS AND METHODS: Perfusion parameters—CBV, corrected CBV, and leakage coefficient—were measured in enhancing tumor portions and contralateral NAWM of 15 PCNSLs and 20 glioblastomas, respectively. The ratios of CBV and corrected CBV were calculated by dividing the tumor values by those obtained from contralateral NAWM. A paired t test was used to compare tumor K2 and NAWM K2, as well as tumor CBV ratios without and with leakage correction. Comparisons of CBV, corrected CBV, and K2 between PCNSLs and glioblastomas were done by using a 2-sample t test. The diagnostic performance of DSC perfusion MR imaging without and with contrast-leakage correction was assessed with receiver operating characteristic curve analysis. RESULTS: PCNSLs and glioblastomas demonstrated higher K2 than those in their contralateral NAWM. Corrected CBV ratios were significantly higher than the uncorrected ones for both tumors. PCNSLs had lower CBV ratios (P < .001), lower corrected CBV ratios (P < .001), and higher K2 (P = .001) compared with glioblastomas. In differentiating between PCNSLs and glioblastomas, the area under the curve of the CBV ratio, corrected CBV ratio, and K2 were 0.984, 0.940, and 0.788, respectively. CONCLUSIONS: PCNSL can be differentiated from glioblastoma with CBV ratios, corrected CBV ratios, and K2. CBV without contrast-leakage correction seems to have the best diagnostic performance in differentiating the 2 tumors.

BACKGROUND AND PURPOSE: The roles of DTI and dynamic susceptibility contrast-enhanced-PWI in predicting the angiographic vascularity of meningiomas have not been studied. We aimed to investigate if these 2 techniques could reflect the angiographic vascularity of meningiomas.MATERIALS AND METHODS: Thirty-two consecutive patients with meningiomas who had preoperative dynamic susceptibility contrast-enhanced-PWI, DTI, and conventional angiography were retrospectively included. The correlations between angiographic vascularity of meningiomas, classified with a 4-point grading scale, and the clinical or imaging variablesage and sex of patient, as well as size, CBV, fractional anisotropy, and ADC of meningiomaswere analyzed. The meningiomas were dichotomized into high-vascularity and low-vascularity groups. The differences in clinical and imaging variables between the 2 groups were compared. Receiver operating characteristic curve analysis was used to determine the diagnostic performance of these variables.RESULTS: In meningiomas, angiographic vascularity correlated positively with CBV but negatively with fractional anisotropy. High-vascularity meningiomas demonstrated significantly higher CBV but lower fractional anisotropy as compared with low-vascularity meningiomas. In differentiating between the 2 groups, the area under the curve values were 0.991 for CBV and 0.934 for fractional anisotropy on receiver operating characteristic curve analysis.CONCLUSIONS: CBV and fractional anisotropy correlate well with angiographic vascularity of meningiomas. They may differentiate between low-vascularity and high-vascularity meningiomas.

BACKGROUND AND PURPOSE: A common imaging finding in brain abscess and necrotic glioblastoma is a T2 hypointense margin. The features of this hypointense rim on SWI have not been previously described, to our knowledge. We aimed to differentiate abscesses from glioblastomas by assessing the morphology of their lesion margin by using SWI.MATERIALS AND METHODS: T2WI and SWI were performed in 12 abscesses and 20 rim-enhancing glioblastomas. On T2WI and SWI, the prevalence and the border types (complete versus incomplete) of hypointense rims were qualitatively assessed. On SWI, the contour (smooth versus irregular) and the location of hypointense rims relative to the contrast-enhancing rims as well as the prevalence of the "dual rim sign," defined as 2 concentric rims at lesion margins with the outer one being hypointense and the inner one hyperintense relative to cavity contents, were also analyzed.RESULTS: Prevalence and the border types of the hypointense rims on T2WI were not different between abscesses and glioblastomas. On SWI, there were significantly more hypointense rims that were complete (P < .001) and smooth (P < .001), having the same location as the contrast-enhancing rims (P < .001) for abscesses. A dual rim sign was present in 9 of 12 abscesses but absent in all glioblastomas (P < .001).CONCLUSIONS: SWI may be helpful in differentiating pyogenic abscesses from necrotic glioblastomas. The dual rim sign is the most specific imaging feature distinguishing the 2.

BACKGROUND AND PURPOSE: TDLs may be indistinguishable from high-grade gliomas on conventional MR imaging. The role of DTI in differentiating TDLs from high-grade gliomas is not clear, and quantitative comparison between the 2 has not been reported. Here we aimed to differentiate TDLs from high-grade gliomas by using DTI.MATERIALS AND METHODS: DTI was performed in 8 TDLs and 13 high-grade gliomas. The presence of 3 findings (ie, intralesional hyperintensities on the FA map, restricted diffusion in the lesion periphery, and a perilesional hyperintense FA rim) was assessed by visual inspection. The FA and MD values were measured in the central nonenhancing portion, peripheral enhancing portion, and perilesional edema for each lesion and compared between the 2 groups respectively.RESULTS: TDLs had a significantly higher incidence of intralesional hyperintensities on FA maps (P = .049) but a lower incidence of a perilesional hyperintense FA rim (P < .001), compared with those of high-grade gliomas on visual inspection. TDLs had significantly higher FA (P = .004) and lower MD (P = .001) values in the peripheral enhancing portions of the lesions compared with those of high-grade gliomas. In perilesional edema, FA values were significantly higher in high-grade gliomas (P = .001).CONCLUSIONS: DTI is helpful in differentiating TDLs from high-grade gliomas by using visual inspection and quantitative analysis.

BACKGROUND AND PURPOSE: The differentiation of abscesses from glioblastomas and metastases may not always be possible on the basis of DWI. Our hypothesis was that differences in diffusion properties as detected by DTI allow differentiation of abscess from glioblastomas and metastasis. Furthermore, diagnostic performance of tensor metrics quantifying anisotropy or tensor shapes is better than that of ADC in measuring mean diffusivity for this purpose.MATERIALS AND METHODS: DTI was performed in 15 abscesses, 15 necrotic glioblastomas, and 26 cystic metastases. In each lesion, manually segmented into 4 regions of interest (ie, cystic cavity, enhancing rim, and immediate [edema most adjacent to the enhancing rim] and distant zones of edema), FA, ADC, C(l), C(p), and C(s) values were measured and statistically compared among groups and evaluated with ROC curve analysis. The presence of a hyperintense FA rim (a rim of edematous tissue that was hyperintense on the FA map) was assessed visually.RESULTS: Abscess was significantly different from glioblastoma for all tensor metrics measured in the cystic cavity and immediate zone of edema and for all except C(l) in the enhancing rim. Abscess was significantly different from metastasis for all tensor metrics measured in the cystic cavity and enhancing rim and for FA, ADC, and C(l) in immediate zone of edema. The incidence of a hyperintense FA rim was significantly higher in glioblastoma and metastasis compared with abscess. The 3 tensor metrics with the highest performance in differentiating abscess from glioblastoma and metastasis were FA, C(l), and C(s) of the cystic cavity.CONCLUSIONS: DTI is able to differentiate abscess from glioblastoma and metastasis. FA, C(l), and C(s) outperformed ADC in diagnostic performance comparisons.

The purpose of this study is to demonstrate the feasibility of using ultrasound induced BBB-disruption technology to enhance brain-permeable area in a brain tumor model for the enhancement of brain-tumor drug delivery. In our system setup, either 28-kHz non-focused ultrasound or 400-kHz focused ultrasound was used. To examine this, SD rats (n = 14) with C-6 Cell been intestinally implanted to regarded as brain-tumor model. The animals were treated 10 days after tumor implant. During the treatment, the animal were anesthesia I.P., and ultrasound contrast agent was administered I.V. before ultrasound energy excitation to enhance the BBB disruption effect. Blue dye was also administered before animal sacrifice for gross observation of the affected region, and H&E staining were performed to evaluate the ultrasound induced brain tissue damage. BBB-disruptive regions were compared between controlled and ultrasound-treated animals to see the enhancement of the ultrasound treatment. Results confirmed that ultrasound sonication either 28-kHz or 400-kHz sonication can enhance the BBB disruption. The pressure threshold of BBB disruption has been confirmed to be 2.25 MPa and 1 MPa in 28 kHz and 400 kHz, respectively. In the 28-kHz sonication case, the BBB-disruptive region surrounding the tumor area can be increased up to 17 fold. Also, tumor-implant animals which underwent localized BBB disruption didn't affect the animal survival, which indicates the ultrasound-induced BBB disruption is secure. The ultrasound-induced BBB disruption may have the potential for brain tumor treatment in the sense of increase the vessel permeability surrounding the brain tumor to increase the local drug concentration near brain tumor.

BACKGROUND AND PURPOSE: Differentiating between primary cerebral lymphoma and glioblastoma multiforme (GBM) based on conventional MR imaging sequences may be impossible. Our hypothesis was that there are significant differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between lymphoma and GBM, which will allow for differentiation between them. MATERIALS AND METHODS: Preoperative diffusion tensor imaging (DTI) was performed in 10 patients with lymphoma and 10 patients with GBM. Regions of interest were placed in only solid-enhancing tumor areas and the contralateral normal-appearing white matter (NAWM) to measure the FA and ADC values. The differences in FA and ADC between lymphoma and GBM, as well as between solidenhancing areas of each tumor type and contralateral NAWM, were analyzed statistically. Cutoff values of FA, FA ratio, ADC, and ADC ratio for distinguishing lymphomas from GBMs were determined by receiver operating characteristic curve analysis. RESULTS: FA and ADC values of lymphoma were significantly decreased compared with NAWM. Mean FA, FA ratio, ADC (10 3 mm 2 /s), and ADC ratios were 0.140 0.024, 0.25 0.04, 0.630 0.155, and 0.83 0.14 for lymphoma, respectively, and 0.229 0.069, 0.40 0.12, 0.963 0.119, and 1.26 0.13 for GBM, respectively. All of the values were significantly different between lymphomas and GBM. Cutoff values to differentiate lymphomas from GBM were 0.192 for FA, 0.33 for FA ratio, 0.818 for ADC, and 1.06 for ADC ratio. CONCLUSIONS: The FA and ADC of primary cerebral lymphoma were significantly lower than those of GBM. DTI is able to differentiate lymphomas from GBM.

BACKGROUND AND PURPOSE:The differentiation between classic and atypical meningiomas may have implications in preoperative planning but may not be possible on the basis of conventional MR imaging. Our hypothesis was that classic and atypical meningiomas have different patterns of intratumoral water diffusion that will allow for differentiation between them. MATERIALS AND METHODS:Preoperative diffusion tensor imaging (DTI) was performed in 12 classic and 12 atypical meningiomas. Signal intensity of solid-enhancing tumor regions on diffusion-weighted trace images and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps was assessed. Regions of interest (ROIs) were placed in solid-enhancing regions, peritumoral edema, and contralateral normal-appearing white matter (NAWM) to measure tensor metrics including major (lambda(1)), intermediate (lambda(2)) and minor eigenvalues (lambda(3)) and FA and ADC values. Distribution of tensor shapes within enhancing tumors was calculated for all tumors. Differences between classic and atypical meningiomas in tumor signal intensity, intratumoral and peritumoral tensor metrics, as well as tensor shapes distribution were statistically analyzed. RESULTS:A significantly greater proportion of atypical meningiomas were isointense and hypointense on ADC maps (P = .007). Classic meningiomas had significantly lower FA (P = .012), higher ADC (P = .011), greater lambda(2) (P = .020) and lambda(3) (P = .003). There was significantly more spherical diffusion in classic than in atypical meningiomas (P = .020). All diffusion tensor metrics for peritumoral edema of the 2 tumor groups did not differ. CONCLUSION:DTI showed that intratumoral microscopic water motion is less organized in classic than in atypical meningiomas. This feature may allow for noninvasive differentiation between classic and atypical meningiomas.

Rosai-Dorfman disease (RDD) is an idiopathic proliferation of histiocytes that affects the lymph nodes. Central nervous system involvement in the absence of nodal disease is extremely rare. On neuroimaging studies, intracranial RDD appears as solitary or multiple well-circumscribed, dura-based lesions. The authors report on two cases of RDD with locally aggressive features including dural sinus invasion, which to their knowledge has never before been described. A 60-year-old woman presented with progressive dizziness and vertigo that had lasted for 1 week. Cranial computerized tomography and magnetic resonance imaging revealed an extraaxial homogeneous lobulated enhancing mass involving the right occipital lobe and the right cerebellar hemisphere. Invasion of the right transverse sinus was identified on a cerebral digital subtraction angiogram. A 59-year-old man with no prior medical illness experienced progressive weakness of both upper extremities and a partial complex seizure. Magnetic resonance imaging of his brain revealed a well-circumscribed enhancing mass in the left frontal lobe with extension to the right frontal lobe and invasion of the superior sagittal sinus. Both patients underwent resection of their brain masses. Pathological studies identified the disease as RDD in both patients.

DNA microaarays are popular tools for large-scale analysis of gene expression in the brain. Combine laser capture microdisection and quantitative real-time reverse transcription polymerase chain reaction technologies, such large-scale expression analysis can be successfully addressed in well-defined tissue specimens. We analyzed the gene expression patterns in three glioblastoma tissue and two control brain samples obtained from the operation by dye-swapping method using cDNA microarray. The differential expression of approximately 4,192 cDNAs was examined. Data after normalization, there are 7 up regulation genes, and 34 down regulation genes, which are 3 times of microarray expression values more or less then the control.

Exonuclease 1 (Exo1) is a 5'-3' exonuclease that interacts with MutS and MutL homologs and has been implicated in the excision step of DNA mismatch repair. To investigate the role of Exo1 in mammalian mismatch repair and assess its importance for tumorigenesis and meiosis, we generated an Exo1 mutant mouse line. Analysis of Exo1(-/-) cells for mismatch repair activity in vitro showed that Exo1 is required for the repair of base:base and single-base insertion/deletion mismatches in both 5' and 3' nick-directed repair. The repair defect in Exo1(-/-) cells also caused elevated microsatellite instability at a mononucleotide repeat marker and a significant increase in mutation rate at the Hprt locus. Exo1(-/-) animals displayed reduced survival and increased susceptibility to the development of lymphomas. In addition, Exo1(-/-) male and female mice were sterile because of a meiotic defect. Meiosis in Exo1(-/-) animals proceeded through prophase I; however, the chromosomes exhibited dynamic loss of chiasmata during metaphase I, resulting in meiotic failure and apoptosis. Our results show that mammalian Exo1 functions in mutation avoidance and is essential for male and female meiosis.

The kinetics of water-gas shift reaction on Ni-Mo-Y zeolite has been studied. The intrinsic reaction rate was obtained experimentally in a Carberry type Continuous-Stirred-Tank-Reactor (CSTR). The gas-solid film resistance was eliminated by high speed rotation of the pellets and the pore diffusion resistance was minimized by selecting pellets of small size (∼1.4 mm). The reaction temperature and pressure ranged from 176° - 400°C and 4–69 bars respectively. The rate is kinetics controlled at low temperatures (176° -232°C) and pore diffusion controlled at higher temperatures (260° -400°C). The rate equation was found to be Lanqmuir-Hinshel wood type with two parameters. A possible reaction mechanism was proposed and discussed. Also, the catalyst was found of possessing excellent resistance to H2S and NH3 poisoning. Catalytic deactivation by carbon deposition or poisoning of phenol and benzine was investigated and a deactivation model was established which described the activity decay accurately. Moreover, Y zeolite was demonstrated to be superior than other catalysts in reactivity under identical test conditions.