Imaging Biomarkers For Renal Tumors In Adults Derived From Intravoxel Incoherent Motion Diffusion-weighted Imaging And Pathologic Analysis

Part 1 Measurement and scan reproducibility of parameters of intravoxel incoherent motion diffusion-weighted imaging in renaltumor and normal renal parenchyma at 3.0 T MRPurpose:To estimate measurement and short-term scan reproducibility of parameters of intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI)in renal tumors,normal renal cortex,and medulla.Materials and Methods:Twenty-five renal tumors and twenty-three contralateral normal kidneys in twenty-four patients were examined twice within 24-48 h using IVIM-DWI1 and IVIM-DWI2 with nine and sixteen b values,respectively at 3.0 T MR scanner.Regions of interests(ROIs)were placed in solid part of tumor,normal cortex,and medulla to derive IVIM-DWI parameters.Differences in parameters between two IVIM-DWI sets and intra-observer,inter-observer,and scan-rescan differences were assessed using tow-sample t-tests.Intra-class correlation coefficient(ICC)was calculated to evaluate intra-observer,inter-observer,and scan-rescan agreement analysis of the parameters of IVIM-DWI.Intra-observer,inter-observer,and scan-rescan reproducibility were assessed by measuring coefficient of variation(CV)and 95%Bland—Altman limits of agreements(BA-LA).Results:There was no significant differences in ADC,D,D*,and f in renal tumors,normal renal cortex and medulla between two measurements by one observer,measurements by two observers,scan and a short-term rescan,and two sets of IVIM-DWI.The intra-and inter-observer ICC of ADC,D,D*,and f of renal tumors,ADC and D of normal renal cortex and medulla were 0.723-0.993.The intra-and inter-observer ICC of D*and f of normal renal cortex and medulla were 0.124-0.961.The scan-rescan ICC was 0.871-0.927 for ADC and 0.844-0.823 for D in renal tumors.Generally the ICCs were lower than 0.20 for D*and f in renal tumors,ADC,D,D*,and f in normal renal cortex and medulla.Intra-observer reproducibility of renal tumors,normal renal cortex,and medulla was excellent for ADC(CV:3.45%-5.34%,BA-LA:-14%-18%)and D(CV:3.65%-6.04%,BA-LA:-18%-19%),good for f(CV:11.96%-16.08%,BA-LA:-76.40%-92.1%except f of medulla with CV of 32.59%and BA-LA of-76.4%-92.1%in IVIM-DWI1),and poor for D*(CV:25.0%-75.4%,BA-LA:-111%-150%).The same order was in inter-observer reproducibility analysis.Reproducibility of scan-rescan was worse than that of inter-and intra-observer.Renal medulla showed worse reproducibility than renal tumors and normal cortex.The parameters of IVIM-DWI2 had a better reproducibility than IVIM-DWI1.Conclusion:Excellent reproducibility evaluation for ADC and D,good for f,and poor for D*derived from IVIM-DWI were observed in renal tumors,normal renal cortex,and medulla.D*has limited reliability and scan-rescan reproducibility should be improved.Part 2 The effect of number and distribution of b value on the parameters of intravoxel incoherent motion diffusion-weighted imaging and on their diagnostic efficiencies on differentiating renal benign and malignant lesionsPurpose:To estimate the effect of number and distribution of b value on parameters of intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI)and their diagnostic efficiencies on differentiating renal benign and malignant lesions.Materials and Methods:108 renal lesions and 101 contralateral normal kidneys in 106 patients were examined by conventional pre-and post-contrast MR and four sets of IVIM-DWI with different number and distribution of b value at 3.0 T MR scanner.Regions of interests(ROIs)were placed in solid part of tumor and contralateral normal cortex to derive IVIM-DWI parameters of each set.Differences in parameters of renal lesions and normal renal cortex among four sets of IVIM-DWI were assessed using one-way analysis of variance(ANOVA).All lesions were classified into benign and malignant groups,and differences in ADC,D,D*,and f between two groups were compared by using two-sample t-test.Receiver operating characteristic(ROC)curve analysis was performed to test the ability of ADC,D,D*,and f of each set of IVIM-DWI in differentiating renal malignant lesions from benign ones by calculating area under curve(AUC),sensitivity,specificity and Youden’s Index.Results:There were significant differences in ADC of renal lesions among four sets of IVIM-DWI and the ADC value of IVIM-DWI4 was significantly lower(1.66X 10-3 mm2/s)than the other three(1.79-1.85)X 10-3 mm2/s.No significant difference was achieved in D,D*,and f of renal lesions among four sets.Significant differences were found in ADC,D,and f of normal renal cortex,ADC and D of IVIM-DWI4 were lower than those of the other three groups while f was higher than the others.There was no significant difference in D*of renal cortex among four sets.ADC and D of malignant renal lesions were(1.73-1.92)X 10-3 mm2/s and(1.26-1.38)X 10-3 mm2/s,respectively,significantly higher than ADC of(1.25-1.55)X 10-3 mm2/s and D of(0.77-0.85)X 10-3 mm2/s of benign ones.No significant differences in D*and f were found between malignant and benign renal lesions.ADC and D of each group had moderate diagnostic efficiency in distinguishing malignant renal lesions from benign ones while D*and f had no significantly diagnostic effciency.Among the parameters of four sets,D of IVIM-DWI1 was more effective for distinguishing malignant lesions from benign ones(with an AUC of 0.788):A threshold value of larger than 1.05X 10-3 mm2/s permitted distinction with sensitivity of 79.3%and specificity of 93.7%.Conclusion:The number and distribution have impact on ADC and D of renal lesions and ADC,D,and f of normal renal cortex while have no impact on the diagnostic efficiency of ADC and D in distinguishing malignant renal lesions from benign ones.D is more effective than ADC in identifying malignant renal lesions from benign ones.Part 3 Preliminary study on diagnostic value of parameters of intravoxel incoherent motion diffusion-weighted imaging in identifying different pathological types of renal tumorsPurpose:To estimate diagnostic value of parameters of intravoxel incoherent motion diffusion-weighted imaging in identifying different pathological types of renal tumors.Materials and Methods:157 patients with 159 renal tumors were examined by conventional MR(with contrast)and IVIM-DWI at 3.0 T MR scanner.All lesions were performed by partial or radical nephrectomy and got pathological proof.Regions of interests(ROIs)were placed in solid part of tumor on the maximal lesion diameter image to derive IVIM-DWI parameters.Differences in ADC,D,D*,and f among each pathological type tumors were assessed using Kruskal-Wallis H-test.All lesions were classified into three groups of clear cell renal cell carcinomas(ccRCCs),non-clear cell renal cell carcinoma(non-ccRCCs),and benign renal tumors to assess differences in ADC,D,D*,and f among three groups by using one-way analysis of variance(ANOVA).Receiver operating characteristic(ROC)curve analysis was performed to test the ability of ADC,D,D*,and f in differentiating ccRCCs from non-ccRCCs,ccRCCs from benign renal tumors,and benign renal tumors from non-ccRCCs by calculating area under curve(AUC),sensitivity,specificity and Youden’s Index.Results:All tumors were pathologically proved 121 ccRCCs,20 non-ccRCCs,and 18 benign renal tumors.ccRCCs had a significantly higher ADC value of(1.92 ±0.39)×10-3 mm2/s than that of non-ccRCCs of(1.46± 0.50)X 10-3 mm2/s and benign renal tumors of(1.32 ± 0.34)X 10-3 mm2/s.There were significant differences in D among ccRCCs,non-ccRCCs,and benign renal tumors,with a D value of(1.40±0.41)X 10-3 mm2/s,(1.08±0.41)X 10-3 mm2/s,and(0.79 ±0.22)X 10-3 mm2/s,respectively.There were no significant differences in D*and f among three groups of tumors.ADC,D,and D*were effective on differential diagnosis of ccRCCs and non-ccRCCs,among which ADC had the largest diagnostic efficiency(AUC:0.762,YI:0.535).D was more effective(with an AUC of 0.927 and YI of 0.799)than ADC(with an AUC of 0.873 and YI of 0.649)for distinguishing ccRCCs from benign renal tumors:A threshold value of larger than 1.05 X 10-3 mm2/s permitted distinction with sensitivity of 83.5%and specificity of 94.4%.D and D*were effective for differential diagnosis of benign renal tumors and non-ccRCCs:A threshold value of ≤1.05×10-3 mm2/s for D and>36.2×10-3 mm2/s for D*permitted distinction with sensitivity of 94.4%and 83.3%,and specificity of 60.0%and 65.0%,respectively.Conclusion:Parameters of IVIM-DWI have efficiency on identifying ccRCC,non-ccRCC,and benign renal tumors and can provide more valuable diagnostic information.Part 4 Preliminary study of value of intravoxel incoherent motion diffusion-weighted imaging in assessment of pathological grade and angiogenesis of clear cell renal cell carcinomaPurpose:To investigate the value of IVIM-DWI in assessing pathological grade and angiogenesis of clear cell renal cell carcinoma(ccRCC).Material and methods:Consecutive patients with renal tumors pathologically proved ccRCCs undwent 3.0 T MR including pre-,post-contrast MRI and IVIM-DWI using nine b values were analyzed retropspectively.The number of cell nuclei and tumor cell density in HE slice and microvessele density(MVD)with CD31 as the marker were calculated.All tumors were divided into low grade-ccRCC group(Grade 1 and 2)and high grade-ccRCC(Grade 3 and 4)group according to WHO/ISUP classification.Regions of interests(ROIs)were placed in solid part of tumor on the maximal lesion diameter image to derive IVIM-DWI parameters.Differences in ADC,D,D*,and f between two groups were compared by using two-sample t-test.The correlation between IVIM-DWI parameters and tumor cell density,MVD and pathological grade was assessed by using Spearman or Pearson correlation test.Receiver operating characteristic(ROC)curve analysis was performed to test the ability of IVIM-DWI parameters in identifying pathological grade and angiogenesis of ccRCC.Results:A total of 114 ccRCCs(35 with Grade 1,54 with Grade 2,19 with Grade 3,and 6 with Grade 4)were classified into low grade-ccRCC(LG-ccRCC)and high grade-ccRCC(HG-ccRCC).There were significant differences in ADC,D,number of tumor cell and tumor cell density between LG-ccRCC and HG-ccRCC while no significant difference were achieved in D*,f,and MVD.ADC and D value of(1.99 ±0.39)×10-3 mm2/s and(1.52±0.42)×10-3 mm2/s,respectively in LG-ccRCC were significantly higher than those of(1.76±0.44)X 10-3 mm2/s and(1.10±0.33)X 10-3 mm2/s,respectively in HG-ccRCC.ADC and D were negatively correlated with tumor cell density and pathological grade while none parameters of IVIM-DWI were correlated with MVD.D was more effective than ADC for distinguishing LG-ccRCC from HG-ccRCC(with an AUC of 0.785 and YI of 0.490):A threshold value of larger than 1.23 ×10-3 mm2/s permitted distinction with sensitivity of 73.0%and specificity of 76.0%.Conclusion:Parameters of IVIM-DWI cannot provide diagnostic information for identifying angiogenesis of ccRCC but parameter D is more effective than ADC in evaluation pathological grade of ccRCC.