Diffusion Kurtosis Imaging Reflects GFAP, TopoIIα, and MGMT Expression in Astrocytomas.

OBJECTIVE: Preliminary study of magnetic resonance (MR) diffusion kurtosis imaging (DKI) assessing the pathological glial fibrillary acidic protein (GFAP), TopoIIα, and O 6-methylguanine-DNA methyltransferase (MGMT) expression in astrocytomas. MATERIALS AND METHODS: This study was approved by the local ethics committee, and informed consent was obtained from all participants. Sixty-six cases with pathologically proven astrocytomas were enrolled in this study; of which, 34 were high grade and remaining 32 were low grade. They patients underwent conventional MRI head scan, DKI scan, and enhanced scan under the same conditions. Fractional anisotropy (FA) and mean kurtosis (MK) calculated from DKI, as well as GFAP, TopoIIα, and MGMT expression level were compared prospectively between high and low-grade astrocytomas. Spearman rank correlation analysis was used for comparing values of DKI and GFAP, TopoIIα, and MGMT expression level in the two groups. RESULTS: The MK values were significantly higher in high-grade astrocytomas than those in low-grade astrocytomas (P < 0.05); FA values demonstrated no significant difference between the two groups (P = 0.331). GFAP expression level was significantly lower in high-grade astrocytomas than in low-grade astrocytomas (P < 0.05). Topo-IIα expression level were significantly higher in high-grade astrocytomas than in low-grade astrocytomas (P < 0.05). There was no significant difference in MGMT expression level between the two groups (P = 0.679). MK values were negatively correlated with the expression of GFAP (r = -0.836; P = 0.03), however, they were positively correlated with the expression of Topo-IIα (r = 0.896; P = 0.01). FA values were not correlated with the expression of GFAP (r = 0.366; P = 0.05), Topo-IIα (r = -0.562; P = 0.05), and MGMT (r = -0.153; P = 0.10). CONCLUSION: MK, the DKI parameter values of astrocytomas, was significantly correlated to the expression of GFAP and TopoIIα. To a certain extent, applying DKI may provide the biological behavior of tumor cell differentiation, proliferation activity, invasion and metastasis, and can guide individual treatment.

Differentiating high-grade glioma recurrence from pseudoprogression: Comparing diffusion kurtosis imaging and diffusion tensor imaging.

PURPOSE: To compare the diagnostic value of DKI and DTI in differentiation of high-grade glioma recurrence and pseudoprogression (PsP). METHOD: Forty patients with high-grade gliomas who exhibited new enhancing lesions (24 high-grade glioma recurrence and 16 PsP) within 6 months after surgery followed by completion of chemoradiation therapy. All patients underwent repeat surgery or biopsy after routine MRI and DKI (including DTI). They were histologically classified into high-grade glioma recurrence and PsP groups. DKI (mean kurtosis [MK], axial kurtosis [Ka], and radial kurtosis [Kr]) and DTI (mean diffusivity [MD] and fractional anisotropy [FA]) parameters in the enhancing lesions and in the perilesional edema were measured. Inter-group differences between high-grade glioma recurrence and PsP were compared using the Mann-Whitney U test The receiver operating characteristic (ROC) curve was used to assess differential diagnostic efficacy of each parameter, and Z-scores were used to compare the value between DKI and DTI. RESULTS: Relative MK (rMK) was significantly higher and relative MD (rMD) was significantly lower in the enhancing lesions of high-grade glioma recurrence compared to PsP (P <  0.001, P = 0.006, respectively). The AUC was 0.914 for rMK and 0.760 for rMD, and this difference was significant (P = 0.030). In the perilesional edema, rMK values were significantly higher and rMD values were significantly lower in high-grade glioma recurrence compared to PsP (P <  0.001, P =  0.005). CONCLUSIONS: DKI had superior performance in differentiating high-grade glioma recurrence from PsP, and rMK appeared to be the best independent predictor.

Combination value of diffusion-weighted imaging and dynamic susceptibility contrast-enhanced MRI in astrocytoma grading and correlation with GFAP, Topoisomerase IIα and MGMT.

The present study aimed to investigate the value of diffusion-weighted imaging (DWI) combined with dynamic susceptibility contrast-enhanced (DSC) magnetic resonance imaging (MRI) scans in astrocytoma grading, and correlated MRI scan parameters of values of apparent diffusion coefficient (ADC) and relative cereberal blood volume (rCBV) with the immunohistochemical (IHC) indices of glial fibrillary acidic protein (GFAP), topoisomerase IIα (Topo IIα) and O 6-methylguanine-DNA methyltransferase (MGMT). A total of 123 patients with pathologically confirmed astrocytomas of differing grades underwent DWI and DSC scans. The values of the ADC and relative cerebral blood volume rCBV were compared with the grade II-IV astrocytomas. Receiver operating characteristic curves were used to compare astrocytoma grading efficiency of ADC, rCBV and the combination of the two values. The parameters of ADC and rCBV with GFAP, Topo IIα and MGMT indices were then correlated. The differences in ADC values were significant between the grades II, III and IV astrocytomas, and the rCBV values for grades II, III and IV were also significant. The combination of DWI and DSC demonstrated the highest values for area under curve in identifying grades II and III, and identifying grades III and IV, respectively. GFAP displayed a positive correlation with ADC and a negative correlation with rCBV. Topo IIα exhibited a negative correlation with ADC, and a positive correlation with rCBV. No correlation was observed between MGMT and ADC or rCBV. The combined application of DWI and DSC may increase astrocytoma grading accuracy. Values of ADC and rCBV exhibit certain correlations with IHC indices, and may predict degree of malignancy of astrocytoma.

Diffusion Kurtosis Imaging Reflects Glial Fibrillary Acidic Protein (GFAP), Topo IIα, and O6-Methylguanine-DNA Methyltransferase (MGMT) Expression in Astrocytomas.

BACKGROUND Astrocytomas are the most common primary brain neoplasms. Biological indicators of astrocytomas can reflect its biological characteristics. The aim of this study was to assess the expression of the pathological glial fibrillary acidic protein (GFAP) Topo IIα and O6-methylguanine-DNA methyltransferase (MGMT) in astrocytomas using magnetic resonance (MR) diffusion kurtosis imaging (DKI) to evaluate the biological characteristics of astrocytomas. MATERIAL AND METHODS Sixty-six patients with pathologically proven astrocytomas were enrolled in this study. All patients underwent conventional MRI head scanning, DKI scanning, and enhanced scanning under the same conditions. Spearman's rank correlation analysis and Bonferroni correction were used to compare the values of DKI and the expression levels of GFAP, Topo IIα, and MGMT between the 2 groups. RESULTS Mean kurtosis (MK) values were negatively correlated with the expression of GFAP (r=-0.836; P=0.03). However, these were positively correlated with the expression of Topo IIα (r=0.896; P=0.01). Moreover, fractional anisotropy (FA) values were not correlated with the expression of GFAP (r=0.366; P=0.05), Topo IIα (r=-0.562; P=0.05), or MGMT (r=-0.153; P=0.10). CONCLUSIONS MK was significantly associated with the expression of GFAP and Topo IIα. To a certain extent, applying DKI may show the biological behavior of tumor cell differentiation, proliferation activity, invasion, and metastasis, and guide individual treatment.

Brainstem Congestion Due to Dural Arteriovenous Fistula at the Craniocervical Junction: Case Report and Review of the Literature.

BACKGROUND: Dural arteriovenous fistulas (DAVFs) at the craniocervical junction are rare. Clinical manifestations range from acute or chronic myelopathy to subarachnoid hemorrhage to brainstem dysfunction. We encountered 4 cases of DAVFs at the craniocervical junction with progressive brainstem dysfunction and investigated the typical magnetic resonance imaging (MRI) features using T2-weighting imaging, susceptibility-weighted imaging, diffusion-weighted imaging, and contrast-enhanced imaging. Literature review revealed 10 case reports of DAVFs at the craniocervical junction manifesting with brainstem dysfunction. CASE DESCRIPTION: Four patients presented with DAVFs at the craniocervical junction with progressive brainstem dysfunction. Two patients underwent midline suboccipital craniotomy and C1 laminectomy, and 1 patient underwent transarterial endovascular embolization with Onyx 18 under general anesthesia. All neurologic deficits gradually improved after the operation. In the fourth case, the patient received conservative treatment and did not undergo any surgical procedure. MRI showed high signal intensity on T2-weighted imaging, magnetic resonance angiography, and magnetic resonance venography. Abnormal dilated vessels and flow-void signs around the lesions were detected on susceptibility-weighted imaging and contrast-enhanced images. Two cases revealed no abnormalities and had improved neurological deficits than those showed on diffusion-weighted imaging. CONCLUSIONS: Susceptibility-weighted imaging, diffusion-weighted imaging, or contrast-enhanced scanning should be used during MRI examination of patients with progressive brainstem dysfunction to differentiate DAVFs at the craniocervical junction from other diseases, such as glioma or infection. Prompt diagnosis using MRI is of great significance in producing good functional outcomes of the patients.

The value of multi ultra high-b-value DWI in grading cerebral astrocytomas and its association with aquaporin-4.

OBJECTIVE: To investigate the value of multi-ultrahigh-b-value diffusion-weighted imaging (UHBV-DWI) in differentiating high-grade astrocytomas (HGAs) from low-grade astrocytomas (LGAs), analyze its association with aquaporin (AQP) expression. METHODS: 40 astrocytomas divided into LGAs (N = 15) and HGAs (N = 25) were studied. Apparent diffusion coefficient (ADC) and UHBV-ADC values in solid parts and peritumoral edema were compared between LGAs and HGAs groups by the t-test. Using receiver operating characteristic curves to identify the better parameter. Using real time polymerase chain reaction to assess AQP messenger ribonucleic acid (mRNA). Using spearman correlation analysis to assess the correlation of AQP mRNA with each parameter. RESULTS: ADC values in solid parts of HGAs were significantly lower than LGAs (p = 0.02), while UHBV-ADC values of HGAs were significantly higher than LGAs (p < 0.01). Area under the curve (AUC) of UHBV-ADC (0.810) was larger than ADC (0.713), and the area under the curve of UHBV-ADC was significantly higher than that of ADC (p = 0.041). AQP4 mRNA was significantly higher in HGAs than that in LGAs (p < 0.01); there was less AQP9 mRNA and no AQP1 mRNA in LGAs and HGAs groups (p > 0.05); ADC value showed a negative correlation with AQP4 mRNA (r = -0.357; p = 0.024). UHBV-ADC value positively correlated with the AQP4 mRNA (r = 0.646; p < 0.01). CONCLUSION: UHBV-DWI allowed for a more accurate grading of cerebral astrocytoma than DWI, and UHBV-ADC value may be related with the AQP4 mRNA levels. UHBV-DWI could be of value in the assessment of astrocytoma. Advances in knowledge: UHBV-DWI generated by multi UHBV could have particular value for astrocytoma grading, and the level of AQP4 mRNA might be potentially linked to the change of UHBV-DWI parameter, and we might find the exact reason for the difference of UHBV-ADC between the LGAs and HGAs.

Grading of Gliomas by Using Radiomic Features on Multiple Magnetic Resonance Imaging (MRI) Sequences.

BACKGROUND Gliomas are the most common primary brain neoplasms. Misdiagnosis occurs in glioma grading due to an overlap in conventional MRI manifestations. The aim of the present study was to evaluate the power of radiomic features based on multiple MRI sequences - T2-Weighted-Imaging-FLAIR (FLAIR), T1-Weighted-Imaging-Contrast-Enhanced (T1-CE), and Apparent Diffusion Coefficient (ADC) map - in glioma grading, and to improve the power of glioma grading by combining features. MATERIAL AND METHODS Sixty-six patients with histopathologically proven gliomas underwent T2-FLAIR and T1WI-CE sequence scanning with some patients (n=63) also undergoing DWI scanning. A total of 114 radiomic features were derived with radiomic methods by using in-house software. All radiomic features were compared between high-grade gliomas (HGGs) and low-grade gliomas (LGGs). Features with significant statistical differences were selected for receiver operating characteristic (ROC) curve analysis. The relationships between significantly different radiomic features and glial fibrillary acidic protein (GFAP) expression were evaluated. RESULTS A total of 8 radiomic features from 3 MRI sequences displayed significant differences between LGGs and HGGs. FLAIR GLCM Cluster Shade, T1-CE GLCM Entropy, and ADC GLCM Homogeneity were the best features to use in differentiating LGGs and HGGs in each MRI sequence. The combined feature was best able to differentiate LGGs and HGGs, which improved the accuracy of glioma grading compared to the above features in each MRI sequence. A significant correlation was found between GFAP and T1-CE GLCM Entropy, as well as between GFAP and ADC GLCM Homogeneity. CONCLUSIONS The combined radiomic feature had the highest efficacy in distinguishing LGGs from HGGs.

Comparison of the values of MRI diffusion kurtosis imaging and diffusion tensor imaging in cerebral astrocytoma grading and their association with aquaporin-4.

OBJECTIVE: To compare the value of MRI diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in grading cerebral astrocytomas and to analyze the correlation of respective parameters with aquaporin-4 (AQP4) expression. METHODS: Sixty patients with cerebral astrocytoma, including low-grade astrocytomas (LGA, n = 25) and high-grade astrocytomas (HGA, n = 35), were studied. The values of DKI parameters (mean kurtosis [MK], radial kurtosis [Kr], and axial kurtosis [Ka]) and DTI parameters (fractional anisotropy, mean diffusivity [MD]) corrected by contralateral normal-appearing white matter in the solid parts of the tumors and peritumoral edema were compared. Receiver operating characteristic curves were used to identify the best parameters. Spearman correlation analysis was conducted to assess the correlation of AQP4 expression with each parameter value. RESULTS: MK, Ka, and Krvalues were significantly higher whereas MD values were significantly lower in the solid parts of HGA, as compared to those of LGA. MK value in peritumoral edematous tissue was significantly higher in HGA as compared to that in LGA. Ka (0.889) had the largest area under the curve (AUC), followed by MK (0.840), Kr (0.750), and MD (0.764). The AUC of Kaand MK was significantly higher than that of MD. Optimal thresholds for MK, Ka, Kr, and MD for differentiating the two groups were 0.490, 0.525, 0.432, and 1.493, respectively. The AQP4 expression in the solid parts of the tumors was significantly higher in HGAs. MK, Kr, Kavalues positively correlated with the AQP4 expression, whereas MD showed a slight negative correlation with AQP4. CONCLUSION: Use of DKI improved grading of cerebral astrocytomas when compared with DTI. DKI parameters appeared to reflect the level of AQP4 expression in astrocytomas.

Differentiation of high-grade-astrocytomas from solitary-brain-metastases: Comparing diffusion kurtosis imaging and diffusion tensor imaging.

OBJECTIVE: To compare the value of MRI diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in differentiating high-grade-astrocytomas from solitary-brain-metastases. METHODS: Thirty-one high-grade-astrocytomas and twenty solitary-brain-metastases were retrospectively identified. DKI parameters [mean kurtosis (MK), radial kurtosis (Kr), and axial kurtosis (Ka)] and DTI parameters [fractional anisotropy (FA) and mean diffusivity (MD)] values with and without correction by contralateral normal-appearing white matter (NAWM) in the tumoral solid part and peritumoral edema, were compared using the t-test. Receiver operating characteristic (ROC) curves were used to test for the best parameters. RESULTS: The DKI values (MK, Kr, and Ka) and DTI values (FA and MD) in tumoral solid parts did not show significant differences between the two groups. Corrected and uncorrected MK, Kr, and Ka values in peritumoral edema were significantly higher in high-grade-astrocytomas than solitary-brain-metastases, and MD values without correction were lower in high-grade astrocytomas than solitary-brain-metastases. The areas under curve (AUC) of corrected Ka (1.000), MK (0.889), and Kr (0.880) values were significantly higher than those of MD (0.793) and FA (0.472) values. The optimal thresholds for corrected MK, Kr, Ka, and MD were 0.369, 0.405, 0.483, and 2.067, respectively. CONCLUSION: DKI and directional analysis could lead to improved differentiation with better sensitivity and directional specificity than DTI.

Association between the MTHFR C677T polymorphism and risk of cancer: evidence from 446 case-control studies.

Many molecular epidemiological studies have been performed to explore the association between MTHFR C677T polymorphism and cancer risk in diverse populations. However, the results were inconsistent. Hence, we performed a meta-analysis to investigate the association between cancer risk and MTHFR C677T (150,086 cases and 200,699 controls from 446 studies) polymorphism. Overall, significantly increased cancer risk was found when all eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significantly increased breast cancer risk was found in Asians and Indians, significantly decreased colon cancer risk was found, significantly decreased colorectal cancer risk was found in male population, significantly increased gastric cancer risk was found in Caucasians and Asians, significantly increased hepatocellular cancer risk was found in Asians, significantly decreased adult acute lymphoblastic leukemia (AALL) risk was found in Caucasians, significantly decreased childhood acute lymphoblastic leukemia (CALL) risk was found in Asians, and significantly increased multiple myeloma and NHL risk was found in Caucasians. In summary, this meta-analysis suggests that MTHFR C677T polymorphism is associated with increased breast cancer, gastric cancer, and hepatocellular cancer risk in Asians, is associated with increased gastric cancer, multiple myeloma, and NHL risk in Caucasians, is associated with decreased AALL risk in Caucasians, is associated with decreased CALL risk in Asians, is associated with increased breast cancer risk in Asians, is associated with decreased colon cancer risk, and is associated with decreased colorectal cancer risk in male population. Moreover, this meta-analysis also points out the importance of new studies, such as Asians of HNC, Asians of lung cancer, and Indians of breast cancer, because they had high heterogeneity in this meta-analysis (I(2) > 75%).

Combined value of susceptibility-weighted and perfusion-weighted imaging in assessing who grade for brain astrocytomas.

PURPOSE: To assess the value of combining susceptibility-weighted imaging (SWI) and dynamic susceptibility weighted contrast-enhanced (DSC) perfusion-weighted MRI (PWI) in assessing World Health Organization (WHO)grade for brain astrocytoma . MATERIALS AND METHODS: A total of 94 patients with pathologically confirmed astrocytomas underwent SWI and DSC scans. The evaluation included intratumoral susceptibility signal intensity (ITSS) and relative cerebral blood volume (rCBV) max. The receiver operating characteristic curve (ROC) was used to assess the efficacy of combining two sequences in astrocytoma grading. RESULTS: ITSS within astrocytomas showed significant correlations with rCBV max (r » 0.72; P < 0.01) and with tumor grades (r » 0.92; P < 0.01), and there was also a significant correlation between rCBV and tumor grade (r= 0.77; P < 0.001). The area under the ROC, SWI, PWI,SWI, and PWI, in differentiation of the grades II and III astrocytomas were 0.995, 0.942, and 1.000, respectively;identifying grades III and IV were 0.773, 0.919, and 0.978, respectively; and identifying high and low-grade astrocytomas were 0.999, 0.992, 1.000, respectively. CONCLUSION: ITSS was useful for assessing the WHO tumor grade in this cohort of patients with astrocytoma.The combination of SWI and PWI may improve the diagnostic accuracy of astrocytoma grading.

Association between the XRCC3 T241M polymorphism and risk of cancer: evidence from 157 case-control studies.

The T241M polymorphism in the X-ray cross-complementing group 3 (XRCC3) had been implicated in cancer susceptibility. The previous published data on the association between XRCC3 T241M polymorphism and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and XRCC3 T241M (61,861 cases and 84,584 controls from 157 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ration [OR]=1.07, 95% confidence interval [CI]=1.00-1.13; recessive model: OR=1.15, 95% CI=1.08-1.23; additive model: OR=1.17, 95% CI=1.08-1.28) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of bladder cancer and breast cancer, especially in Caucasians. In addition, significantly decreased lung cancer risk was also observed. In summary, this meta-analysis suggests the participation of XRCC3 T241M in the susceptibility for bladder cancer and breast cancer, especially in Caucasians, and XRCC3 T241M polymorphism is associated with decreased lung cancer risk. Moreover, our work also points out the importance of new studies for T241M association in some cancer types, such as gastric cancer, colorectal cancer, and melanoma skin cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC3 polymorphism in cancer development.

Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis.

The previous published data on the association between the 8-oxo-guanine glycosylase-1 (OGG1) and apurinic/apyrimidinic-endonuclease-1 (APEX1/APE1) polymorphisms and lung cancer risk remained controversial. Several polymorphisms in the OGG1 and APEX1 gene have been described, including the commonly occurring Ser326Cys in OGG1 and Asp148Glu in APEX1. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 37 studies were identified to the meta-analysis, including 9,203 cases and 10,994 controls for OGG1 Ser326Cys (from 25 studies) and 3,491 cases and 4,708 controls for APEX1 Asp148Glu (from 12 studies). When all the eligible studies were pooled into the meta-analysis of OGG1 Ser326Cys polymorphism, significantly increased lung cancer risk was observed in recessive model (OR = 1.17, 95 % CI = 1.03-1.33) and in additive model (OR = 1.21, 95 % CI = 1.03-1.42). In the stratified analysis, significantly increased risk of lung cancer was also observed on the population-based studies (recessive model: OR = 1.26, 95 % CI = 1.08-1.46, additive model: OR = 1.42, 95 % CI = 1.06-1.73) and non-smokers (dominant model: OR = 1.20, 95 % CI = 1.02-1.42, recessive model: OR = 1.20, 95 % CI = 1.02-1.40, additive model: OR = 1.35, 95 % CI = 1.08-1.68). Additionally, when one study was deleted in the sensitive analysis, the results of OGG1 Ser326Cys were changed in Asians (recessive model: OR = 1.16, 95 % CI = 1.06-1.27, additive model: OR = 1.23, 95 % CI = 1.09-1.38). When all the eligible studies were pooled into the meta-analysis of APEX1 Asp148Glu polymorphism, there was no evidence of significant association between lung cancer risk and APEX1 Asp148Glu polymorphism in any genetic model. In the stratified analysis, significantly decreased lung adenocarcinoma risk was observed in recessive model (OR = 0.68, 95 % CI = 0.48-0.97, P (h) = 0.475, I(2) = 0.0 %). Additionally, when one study was deleted in the sensitive analysis, the results of APEX1 Asp148Glu were changed in Asians (recessive model: OR = 1.21, 95 % CI = 1.03-1.43) and smokers (dominant model: OR = 1.62, 95 % CI = 1.08-2.44, additive model: OR = 1.37, 95 % CI = 1.02-1.84). In summary, this meta-analysis indicates that OGG1 Ser326Cys show an increased lung cancer risk in Asians and non-smokers, APEX1 Asp148Glu polymorphism may be associated with decreased lung adenocarcinoma risk, and APEX1 Asp148Glu polymorphism show an increased lung cancer risk in Asians and smokers. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk.