Study On Evaluation Of The Correlation Between Blood Oxygen-level Dependent MRI And Susceptibility-weighted MRI And Pathological Grades Of Renal Cell Carcinoma

PARTⅠClinical value of BOLD-MRI in predicting the pathological grade of clear cell renal cell carcinomaObjective: To assess the clinical value of BOLD-MRI in predicting the pathological grade of clear cell renal cell carcinoma(CRCC), the BOLD-MRI based R2* values were compared between low- and high-grade CRCC, and the relationship between R2* value and hypoxia-in ducible factors α(HIF- α) was analyzed.Material and Methods:Thirty-one consecutive patients with renal mass, 23 men and 8women, underwent MRI from July 2011 to January 2012. And they were also diagnosed with CRCC by histological examination. 5/31 cases were excluded because of no BOLD-MRI examination in 2 cases and no sufficient tumor tissue for R2* measurement in3 cases of cystic renal cell carcinoma. Finally, 26 cases were included in statistic analysis.Image analysis was carried out by two experienced radiologists independently. 3 regions of interest(ROIs), no less than 5 pixels in each ROI, were manually drawn in tumor parenchyma. The R2* for each tumor was the mean by averaging the R2* values of three ROIs. Histopathology was obtained from all masses by radical nephrectomy. The pathologic tumor size was acquired by measuring the largest dimension for each tumor.Fuhrman nuclear grade and immunohistochemical stain(HIF-αanalyses were adopted. On the basis of Fuhrman nuclear grade, all cases were merged into low-grade(Grades I+II)and high-grade groups(Grades III+IV). The reproducibility of R2* measurement was assessed by the intraclass correlation coefficient(ICC). Nonparametric Mann-Whitney test was used to compare the difference of R2* values between low- and high-grade groups.Receiver operating characteristics(ROC) analysis was performed to compare thediagnostic value of the R2* in differentiating low- from high-grade CRCC. An optimal cutoff value with corresponding sensitivity and specificity was obtained. Spearman rank correlation was employed to assess the relationship between the pathologic tumor size and Fuhrman nuclear grade, between R2* value and the Fuhrman nuclear grade, and between the changes of R2* value and the positive ratio of HIF-1α or 2α.Results: Histological analysis revealed grade I(5/26), II(12/26), III(8/26), and IV(1/26). Low-grade group(grades I + II) contained 17 cases and high-grade group(grades III + IV) contained 9 cases. The pathological tumor sizes of CRCCs were shown in Figure1. The mean pathologic tumor size was 5.07 ± 0.52 cm. No significant correlation between Fuhrman grade and pathologic tumor size was seen(P> 0.1). The mean R2* values of CRCCs were 27.72 ± 12.68 s-1and 24.71 ± 13.53 s-1, by two radiologists respectively. The ICC for R2* value was 0.89. The detailed R2* values of all tumor grades were listed in Table 2. Significant differences in R2* values were seen among Fuhrman grades I- III(P<0.005). R2* values of grade III were higher than that of grade I or II(P< 0.01). No significant difference of R2* values was seen between grade I and II(P> 0.05). In grade IV,the number of patients(n = 1) was not sufficient to perform statistical analysis. R2* values of low-grade CRCC were significantly lower than high grade group(P< 0.005). The area under the ROC curve for the differentiation of low- from high-grade CRCC was 0.90. The optimal threshold R2* value was 31.87 s-1, resulting in a sensitivity of 78% and a specificity of 100%. A positive correlation was seen between R2* values and pathological groups of CRCC(r = 0.66, P<.005). The mean HIF-1α and HIF-2α were 3.40 ± 1.98 and2.90 ± 2.17, respectively. There were significant differences between low- and high- grade groups(P< 0.05). A positive correlation was found only between HIF-2α and R2* values(r= 0.580, P< 0.005).Conclusion: BOLD-MRI can serve as one of noninvasive functional imaging methods for assessing the pathological grade with excellent reproducibility. It also reflected indirectly HIF-2α level in CRCC, which is helpful to targeted therapy in the future.PARTⅡ Susceptibility weighted imaging predicted preoperativelypathological grade of clear cell renal cell carcinomaObjective: To assess the value of susceptibility weighted imaging(SWI) in predicting preoperatively the pathological grade of clear cell renal cell carcinoma(CRCC), the intratumoral susceptibility signal intensities(ISS) and necrotic ratio were compared between low- and high-grade CRCC.Material and Methods:A total of 38 consecutive patients underwent MR imaging for evaluation of renal masses during July 2011 and March 2012, and they also had pathological confirmation of CRCC. One patient was excluded because of obviously breathing artifacts. Finally, 37 patients, 23 men and 14 women, were included in statistic analysis. Abdominal SWI was also performed in all the patients. In the image analysis, four image properties were analyzed. 1) A 4-point confidence level scale was used to score the likelihood of presence of ISS on SWI(0 = no ISS, 1 = a focus of ISS less than 0.5 cm in largest dimension in axial planes, 2 = a focus of ISS 0.5-1.0 cm in largest dimension, 3 = a focus of ISS greater than 1.0 cm in largest dimension). 2) The morphology of the ISS was classified into hemorrhage and micro-vascular. The dominant structure of ISS was judged with a 4-point confidence level scale(0 = no ISS in the tumor on SWI; 1= prominently bleeding or hematoma in the tumor on SWI; 2= hemorrhage and vascular structure almost equally presented in the tumor on SWI; 3= prominently vascular structure). 3) The ratio of ISS area to tumor area was scored by a 3-point grading system: 0 = no ISS, 1= the ratio less than half of the tumor on any slice, 2= the ratio greater than half of the tumor in at least one slice. 4) The presence or absence of necrosiswas assessed(0, no necrosis; 1, the presence ofnecrosis). All cases were categorized into low-(Grade Ⅰ+Ⅱ) and high-grade group(Grade Ⅲ +Ⅳ). Nonparametric Mann-Whitney test was used to compare the differences of the likelihood of presence of ISS, dominant structure of ISS, ratio of ISS area to tumor area on SWI, and necrotic ratio between low- and high-grade tumors.Receiver operating characteristics(ROC) analysis was performed to compare the diagnostic value of the four properties in differentiating low- from high-grade tumors.Results:All patients were classified into Grade Ⅰ(12/37), Ⅱ(14/37), Ⅲ(8/37) andⅣ(3/37). There were 26 cases in low-grade group and 11 cases in high-grade group. ISS was absent in 4/37 cases, including 3 cases of Grade Ⅰ and 1 case of Grade Ⅱ, and no significant difference of the likelihood of presence of ISS on SWI was found between lowand high-grade groups(P> 0.05). Simply, it appeared as ’hemorrhage and vascular structure almost equally presented in the tumor’ or ’prominently vascular structure’ in 22/26 patients in low-grade group and as ’prominently bleeding or hematoma in the tumor’in 8/11 patients in high-grade group, a significant difference of dominant structure of ISS was detected between two groups(P< 0.005). The ratio of ISS area to tumor area on SWI was listed in Table 2. The ratio of ISS area to tumor area on SWI was mainly less than 0.5 in low-grade group, but larger than 0.5 in most of patients in high-grade group(6/11). It was significantly higher in high-grade group(P< 0.005). Necrosis in CRCC occurred in 5/26 cases in low-grade group and 11/11 cases in high-grade group, and a significant difference of necrotic ratio in tumor was present between the two groups(P< 0.05). The areas under curve of ROC(AUC) were 0.573 of the likelihood of presence of ISS, 0.948 of the dominant structure of ISS, 0.808 of the ratio of ISS area to tumor area, and 0.712 of necrotic ratio. And only the AUC of the dominant structure of ISS was larger than others(all P< 0.05).Conclusion: 2D-SWI is one noninvasive of magnetic function imaging methods, and it can provide some helpful information for predicting preoperatively the pathological grade of CRCC. The dominant structure of ISS, ratio of ISS area to tumor area, and necrotic ratio can differentiate low- from high-grade CRCC, and the dominant structure of ISS was the best one.PARTⅢ Combination of BOLD-MRI and Susceptibility weighted imaging for predicting preoperatively the pathological grade of clear cellrenal cell carcinomaObjective: To assess the clinical value of the combination of blood oxygen level dependent magnetic resonance imaging(BOLD-MRI) and susceptibility weighted imaging(SWI) in predicting preoperatively the pathological grade of clear cell renal cell carcinoma(CRCC), the R2* value of CRCC and the intratumoral susceptibility signal intensities(ISS)were analyzed.Material and Methods: The magnetic resonance data of 57 patients with CRCC confirmed by pathological examination were analyzed retrospectively. Conventional sequences, BOLD-MRI, and SWI were performed on all patients before radical operation.3 regions of interest(ROIs), no less than 5 pixels in each ROI, was drawn manually in different areas of intratumoral parenchyma for R2* measurement, and the R2* for each tumor is the mean of three R2* values in three ROIs respectively. The morphology of the ISS was classified into hemorrhage and micro-vascular. The dominant structure of ISS was judged with a 4-point confidence level scale(0 = no ISS in the tumor on SWI; 1=prominently bleeding or hematoma in the tumor on SWI; 2= hemorrhage and vascular structure almost equally presented in the tumor on SWI; 3= prominently vascular structure).The ratio of ISS area to tumor area was scored by a 3-point grading system: 0 = no ISS, 1=the ratio less than half of the tumor on any slice, 2= the ratio greater than half of the tumor in at least one slice. All cases were categorized into low-(Grade Ⅰ+Ⅱ) and high-grade group(Grade Ⅲ+Ⅳ) according to the criteria of Fuhrman nuclear grade. Nonparametric Mann-Whitney test was used to compare the differences of R2* values, dominant structure of ISS, and ratio of ISS area to tumor area between low- and high-grade groups.Classification and regression tree(CART) was used to obtain the decision tree and the associated results. The R2* values, dominant structure of ISS, and ratio of ISS area totumor area were treated as independent variables, with pathological grade as the dependent variable.Results:Histological analysis revealed grade I(15/57), II(28/57), III(11/57), and IV(3/57). Low-grade group(grades I + II) contained 43 cases and high-grade group(grades III + IV) contained 14 cases. The R2* value increased with the increased pathological grade, and a significant difference was found between low- and high-grade groups(P<0.005). ISS was absent in 4/57 cases, including 3 cases of Grade Ⅰ and 1 case of Grade Ⅱ. The dominant structure of ISS on SWI appeared as ’hemorrhage and vascular structure almost equally presented in the tumor’ or ’prominently vascular structure’ in 39/43 patients in low-grade group and as ’prominently bleeding or hematoma in the tumor’ in9/14 patients in high-grade group, a significant difference of dominant structure of ISS was detected between two groups(P< 0.005). The ratio of ISS area to tumor area on SWI was mainly less than 0.5 in low-grade group, but larger than 0.5 in most of patients in high-grade group(7/14). It was significantly higher in high-grade group(P < 0.005). In the analysis of CART model, the first categorical variable was R2* value, and the threshold was 37.2-s. There were 45 cases with R2* values ≤37.2s-1, including 42 cases of low-grade CRCC and 3 cases of high-grade CRCC, and 12 cases with R2* values >37.2s-1, including1 case of low-grade CRCC and 11 cases of high-grade CRCC. Furthermore, the diagnostic accuracy increased when the dominant structure of ISS and ratio of ISS area to tumor area were treated as the second and third categorical variables, respectively.Conclusion: BOLD-MRI and SWI characterized the differences between low- and high-grade CRCC from different angles. The combination of them can improve diagnostic precision.