| Part I The value of routine MRI in detecting the isocitrate dehydrogenase 1 (IDH1) gene status in astrogliomasPurpose:The aim of this part was to explore whether routine magnetic resonance imaging (MRI) features helped to noninvasively detect isocitrate dehydrogenase 1 (IDH1) gene status in astrogliomas.Methods:The routine MRI data of 240 patients with pathologically proved astrogliomas in our hospital from January 1st 2011 to August 31st 2013 was retrospectively reviewed. The age and sex of patients and the location, number, diameter, homogeneity, degree of cyst or necrosis, homarraghe, border line, degree of edema and enhancement of lesions were evaluated. The midline shift in brain was also assessed. According to the world healthy organization (WHO) grading in astrogliomas, the lesions were divided into low grade (including WHO grade Ⅱ) (83 patients) and high grade (including WHO grade Ⅲ and IV) (157 patients) by pathological results. IDH1 gene status was determined by IDH1 R132H antibody immunohistochemistry. In low and high grade astrogliomas,52 and 38 patients showed IDH1 mutation. Using the same WHO grading, the imaging parameters of patients with IDH1 mutations and without mutations were compared to determine useful metrics for differentiating the mutation.Results:The astrogliomas with IDH1 mutation were apt to younger patients. IDH1 mutant patients were presented as different degree of enhancement from nonmutant patients. In low grade astrogliomas, no enhancement was showed in 67.30% of IDH1 mutant patients, however in 12.90% of nonmutant patients.45.20% and 41.90% of nonmutant astrogliomas were respectively manifested as mild and marked enhancement. In high grade astrogliomas, IDH1 mutant tumors were presented as mild enhancement (55.30%), however nonmutant tumors were predominantly manifested as obvious enhancement (83.20%). In low grade astrogliomas, IDH1 mutant tumors were prone to frontal location. The diameter of IDH1 mutant tumors was larger than wild tumors. The accident of midline shift in 1DH1 mutant tumors was higher than it in wild tumors. IDH1 nonmutant tumors had a predilection for marked cyst or necrosis and significant edema. In high grade astrogliomas, IDH1 nonmutant tumors had a predilection for unclean inner wall in cystic or necrotic area.Conclusion:Routine MRI was helpful for detect IDH1 gene status in astrogliomas. The location, diameter, degree of cyst or necrosis, edema and enhancement of lesions were shown as differentiating features in mutant and wild low grade astrogliomas. In high grade astrogliomas, the inner wall of cystic or necrotic area and the degree of enchancement in the tumors could provide a possible method for noninvasively detecting IDH1 gene status.Part Ⅱ The value of DTI in detecting the isocitrate dehydrogenase 1 (IDH1) gene status in astrogliomasPurpose:The aim of this part was to explore whether diffusion tensor imaging (DTI) metrics helped to noninvasively detect isocitrate dehydrogenase 1 (IDH1) gene status in astrogliomas.Methods:The DTI data of 222 lesions with pathologically proved astrogliomas in our hospital from January 1st 2011 to August 31st 2013 were retrospectively reviewed. The maximal fractional anisotropy (mFA), minimal apparent diffusion coefficient (mADC), ratio of mFA (rmFA) and ratio of mADC (rmADC) in the tumor volume and paralesional edema area were measured. The contralateral normal posterior limb of the internal capsule was used as normal contrast. Using the same WHO grading, the imaging parameters of patients with IDH1 mutations and without mutations were compared to determine useful metrics for differentiating the mutation. Receiver operating characteristic curve analysis was performed. Sensitivity, specitivity, positive predictive value (PPV) and negative predictive value (NPV) were calculated.Results:The maximal FA and rmFA values had statistical significance between astrogliomas of grade Ⅱ and grade Ⅲ with IDH1 mutations and those without mutations. In grade Ⅱ, the areas under the curve (AUC) for mFA and rmFA were both 0.90. When the cutoff values were 0.17 and 0.24, mFA and rmFA provided the best combination of sensitivity and specifcity in distinguishing between IDH1 mutant and wild astrogliomas. In grade Ⅲ, the AUCs were 0.86 and 0.84. When the cutoff values were 0.24 and 0.29, mFA and rmFA provided the best combination of sensitivity and specifcity in distinguishing IDH1 mutant and wild astrogliomas. The FA and rFA in the paralesional edema area exited the statistical difference between mutant and wild astrogliomas in grade Ⅲ. The minimal ADC value and rmADC value demonstrated statistical significance between astrogliomas of grades Ⅱ and Ⅲ with 1DH1 R132H mutations and those without mutations. In grade Ⅱ, the AUCs for mADC and rmADC were 0.95 and 0.93, respectively, and the cutoff value were 1.14×10-3 mm2/s,1.48. In grade Ⅲ, the AUCs for ADC and rmADC were both 0.88, and the cutoff value were 0.99×10-3 mm2/s and 1.31.Conclusion:FA and ADC, as determined from DTI data, provided a possible method for noninvasively detecting IDH1 mutations in WHO Ⅱ and Ⅲ grade astrogliomas.Part Ⅲ The value of DSC MRI in detecting the isocitrate dehydrogenase 1 (IDH1) gene status in astrogliomasPurpose:The aim of this part was to explore whether dynamic susceptibility contrast MRI (DSC MRI) helped to noninvasively detect isocitrate dehydrogenase 1(IDH1) gene status in astrogliomas.Methods:The DSC MRI data of 91 lesions with pathologically proved astrogliomas in our hospital from January 1st 2011 to August 31st 2013 were retrospectively reviewed. The maximal relative cerebral blood volume (rCBV) in the tumor volume and paralesional edema area and the relative cerebral blood flow (rCBF), relative mean transit time (rMTT) and time to peak (TTP) in the same location with rCBV were measured. The contralateral white matter was used to normalize rCBV, rCBF and rMTT as rCBV ratio, rCBF ratio and rMTT ratio. According to the world healthy organization (WHO) grading in astrogliomas, the lesions were divided into grade Ⅱ (31 patients), grade Ⅲ (24 patients) and grade Ⅳ (36 patients) by pathological results. IDH1 gene status was determined by IDH1 R132H antibody immunohistochemistry. Using the same WHO grading, the imaging parameters of patients with IDH1 mutations and without mutations were compared to determine useful metrics for differentiating the gene status. Receiver operating characteristic curve analysis was performed. Sensitivity, specitivity, positive predictive value (PPV) and negative predictive value (NPV) were calculated.Results:The rCBV ratio had statistical significance between astrogliomas of grade Ⅱ, grade Ⅲ and grade Ⅳ with IDH1 R132H mutations and those without mutations. In grade Ⅱ, the area under the curve (AUC) for rCBV ratio was 0.83. When the cutoff value was 2.20, the sensitivity, specitivity, PPV and NPV were respectively 85.70%,82.40%,87.50% and 80.00%. In grade Ⅲ, the AUC was 0.86. When the cutoff value was 3.14, the sensitivity, specitivity, PPV and NPV were respectively 86.70%,88.90%,80.00% and 92.86%. In grade IV, the AUC was 0.94. When the cutoff value was 5.63, the sensitivity, specitivity, PPV and NPV were respectively 83.30%,100%,54.55% and 100%. The rCBF ratio had statistical significance between astrogliomas of grade Ⅱ and grade Ⅳ with IDH1 mutations and those without mutations. In grade Ⅱ, the area under the curve (AUC) for rCBF ratio was 0.83. When the cutoff value was 2.60, the sensitivity, specitivity, PPV and NPV were respectively 78.60%,88.20%,83.33% and 84.62%. In grade Ⅳ, the AUC was 0.88. When the cutoff value was 4.37, the sensitivity, specificity, PPV and NPV were respectively 86.70%,83.30%,55.56% and 96.30%. The rMTT ratio and TTP in the tumor volume and the rCBV ratio, rCBF ratio, rMTT ratio and TTP in the paralesional edema area were not showed statistical difference between mutant and nonmutant astrogliomas with the same WHO grade.Conclusion:rCBV ratio and rCBF ratio as determined from DSC MRI, provided a new method for noninvasively detecting IDH1 mutations in astrogliomas.Part Ⅳ The value of DCE MRI in detecting the isocitrate dehydrogenase 1 (IDH1) gene status in astrogliomasPurpose:The aim of this part was to explore whether dynamic contrast enhancement MRI (DCE MRI) helped to noninvasively detect isocitrate dehydrogenase 1 (IDH1) gene status in astrogliomas.Methods:The DCE-MRI data of suspected astrogliomas in our hospital from September 1st 2012 to August 31st 2013 were prospectively collected. The age and sex of patients were recorded. And the maximal transfer coefficient between the plasma and extracellular extravascular space (ktrans), maximal fractional volume of the extracellular extravascular space (ve) and the minimal flux rate constant between the extravascular extracellular space and plasma (kep) were measured in the tumor volume and the paralesional edema area. The results of pathological diagnosis and the IDH1 R132H antibody immunohistochemistry were followed.Results:There were 99 patients who accepted the DCE MRI examination including 59 cases (65 lesions) of astrogliomas. According to the world healthy organization (WHO) grading in astrogliomas, the lesions were divided into low grade (including WHO grade Ⅱ) (24 lesions) and high grade (including WHO grade Ⅲ and Ⅳ) (42 lesions) by pathological results. In low grade astrogliomas, the ktrans and ve in IDH1 wild tumors were higher than them in mutant tumors. The areas under the curve (AUC) for ktransand ve were respectively 0.90 and 0.86. When the cutoff values were 0.03 min-1 and 0.05, the sensitivity were both 85.70%, the specificity were both 82.40%, the PPV were both 93.33% and the NPV were both 66.67%. In high grade astrogliomas, the vc in IDH1 wild tumors were higher than them in mutant tumors. The AUC for vc was 0.75. When the cutoff values were 0.20, the sensitivity, specificity, PPV and NPV were respectively 90.30%,60.00%,67.66% and 87.50%.Conclusion:DCE MRI provided a possible method for noninvasively detecting IDH1 mutations in astrogliomas. |
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