Diffusion kurtosis imaging to assess correlations with clinicopathologic factors for bladder cancer: a comparison between the multi-b value method and the tensor method.

OBJECTIVES: To assess the efficacy of diffusion kurtosis imaging (DKI) in differentiating low-grade from high-grade tumors and evaluating the aggressiveness of bladder cancer. METHODS: From January 2017 to July 2017, 35 patients (28 males, 7 females; mean age 63 ± 9 years) diagnosed with bladder cancer underwent diffusion-weighted imaging (DWI) with two types of DKI protocols: (1) multi-b value ranging from 0 to 2000 s/mm2 to obtain mean diffusivity/kurtosis (MDb/MKb) and (2) the tensor method with 32 directions with 3 b values (0, 1000, and 2000s/mm2) to obtain mean/axial/radial diffusivity (MDt/Da/Dr), mean/axial/radial kurtosis (MKt/Ka/Kr), and fractional anisotropy (FA) before radical cystectomy. Comparisons between the low- and high-grade groups, non-muscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC) were performed with the areas under the receiver operating characteristic curves (AUCs). RESULTS: The MKt and Kr values were significantly (p = 0.017 and p = 0.048) higher in patients with high-grade bladder tumors than in those with low-grade tumors. The MKt, Kr, and MKb values were significantly (p = 0.022, p = 0.000, and p = 0.044, respectively) higher in patients with MIBC than in those with NMIBC, while no significant differences (p > 0.05) were found in other values. The AUC of Kr (0.883) was the largest and was significantly higher than those of other metrics (all p < 0.05) for differentiating MIBC from NMIBC, with a sensitivity and specificity of 81.8% and 91.7%, respectively. CONCLUSIONS: Kurtosis metrics performed better than diffusion metrics in differentiating MIBC from NMIBC, and directional kurtosis and Kr metrics may also have great potential in providing additional information regarding bladder cancer invasiveness. KEY POINTS: • Kurtosis metrics performed better than diffusion metrics in differentiating muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC). • Directional kurtosis can provide additional directional microstructural information regarding bladder cancer invasiveness.

Differentiation of clear cell and non-clear cell renal cell carcinomas by all-relevant radiomics features from multiphase CT: a VHL mutation perspective.

OBJECTIVES: To develop a radiomics model with all-relevant imaging features from multiphasic computed tomography (CT) for differentiating clear cell renal cell carcinoma (ccRCC) from non-ccRCC and to investigate the possible radiogenomics link between the imaging features and a key ccRCC driver gene-the von Hippel-Lindau (VHL) gene mutation. METHODS: In this retrospective two-center study, two radiomics models were built using random forest from a training cohort (170 patients), where one model was built with all-relevant features and the other with minimum redundancy maximum relevance (mRMR) features. A model combining all-relevant features and clinical factors (sex, age) was also built. The radiogenomics association between selected features and VHL mutation was investigated by Wilcoxon rank-sum test. All models were tested on an independent validation cohort (85 patients) with ROC curves analysis. RESULTS: The model with eight all-relevant features from corticomedullary phase CT achieved an AUC of 0.949 and an accuracy of 92.9% in the validation cohort, which significantly outperformed the model with eight mRMR features (seven from nephrographic phase and one from corticomedullary phase) with an AUC of 0.851 and an accuracy of 81.2%. Combining age and sex did not benefit the performance. Five out of eight all-relevant features were significantly associated with VHL mutation, while all eight mRMR features were significantly associated with VHL mutation (false discovery rate-adjusted p < 0.05). CONCLUSIONS: All-relevant features in corticomedullary phase CT can be used to differentiate ccRCC from non-ccRCC. Most subtype-discriminative imaging features were found to be significantly associated with VHL mutation, which may underlie the molecular basis of the radiomics features. KEY POINTS: • All-relevant features in corticomedullary phase CT can be used to differentiate ccRCC from non-ccRCC with high accuracy. • Most RCC-subtype-discriminative CT features were associated with the key RCC-driven gene-the VHL gene mutation. • Radiomics model can be more accurate and interpretable when the imaging features could reflect underlying molecular basis of RCC.

Investigation of diffusion kurtosis imaging for discriminating tumors from inflammatory lesions after treatment for bladder cancer.

BACKGROUND: The bladder wall may thicken resulting from chronic inflammation after initial treatment (transurethral resection [TUR] or neoadjuvant chemotherapy), which may mimic the feature of recurrent or residual bladder tumors (RBT). Therefore, it is critical to discriminate RBT from benign lesions after initial treatment. PURPOSE: To investigate whether diffusion kurtosis imaging (DKI) could discriminate RBT from post-therapy bladder inflammatory lesions. STUDY TYPE: Retrospective. SUBJECTS: Fifty patients diagnosed with bladder cancer underwent TUR or received neoadjuvant chemotherapy. FIELD STRENGTH/SEQUENCE: 3.0T MRI/conventional T1 -weighted imaging (T1 WI), T2 WI, and diffusion-weighted imaging (DWI) with nine b-values ranging from 0-2000 s/mm2 . ASSESSMENT: Mean diffusion coefficients (MDa , MDb , and MDc ) and mean kurtosis values (MKa , MKb , and MKc ) were obtained from three different measurement methods. The region of interest (ROI) was placed 1) to encompass the entire portion of the thickening bladder wall or to portions that were the most restricted, with a b-value of 2) 2000 s/mm2 or 3) 1000 s/mm2 . STATISTICAL TESTS: The independent-samples t-test was used to compare the differences between RBT and the inflammatory group. Differences in DKI parameters were analyzed by comparing the areas under the receiver-operator characteristic curves (AUCs). RESULTS: In patients with RBT, the MD (MDa , MDb , MDc ) values were significantly lower and the MK (MKa , MKb , MKc ) values were significantly higher than those in patients in the inflammatory lesions group (all P < 0.01). The AUC of MKb (0.934) was significantly larger than those of MDb , MKa , and MKc (0.793, P < 0.05; 0.694, P < 0.01; 0.719, P < 0.01, respectively). DATA CONCLUSION: MK obtained from DKI provided better performance than conventional DWI in distinguishing RBT from inflammatory lesions after bladder cancer treatment. MK calculated with high b-values setting provided better performance in differentiation. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage 3 J. Magn. Reson. Imaging 2017.

Imaging of upper urinary tract cancer: using conventional MRI and diffusion-weighted MRI with different b values.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) has been considered to be useful in diagnosing upper urinary tract (UUT) disease; however, the value of DW-MRI with different b values has not been reported. PURPOSE: To evaluate the performance of using conventional MRI alone and in combination with DWI with different b values in diagnosing UUT cancer. MATERIAL AND METHODS: Seventy patients with suspected UUT cancer underwent conventional MRI (T1-weighted and T2-weighted) and DW-MRI (b = 500 and 1500 s/mm(2)) on a 3 T-MRI scanner. The ureteroscopic and histopathologic findings were compared with the imaging findings. The utility of detecting UUT cancer using conventional MRI (set A), combined DW-MRI (b = 500 s/mm(2)) and conventional MRI (set B), and combined DW-MRI (b = 1500 s/mm(2)) and conventional MRI (set C) were independently evaluated by two readers. RESULTS: A total of 32 patients had verified cancer; 23 patients had benign UUT diseases, and 15 had no abnormality. Sets B and C had significantly improved diagnostic accuracy for UUT cancer compared with set A; the specificity in diagnosing UUT cancer was significantly improved when using set C compared with sets A and B. In patients without UUT obstructions, improved sensitivity and accuracy in diagnosis was achieved when using sets B and C compared with set A. CONCLUSION: Using DW-MRI in combination with conventional MRI provides increased diagnostic accuracy and sensitivity in patients without UUT obstruction. The combination of conventional MRI and DW-MRI with a higher b value (1500 s/mm(2)) improved the specificity in diagnosing UUT cancer compared to conventional sequences and DW-MRI with a lower b value (500 s/mm(2)).

Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase-deficient renal cell carcinoma.

Germline or somatic loss-of-function mutations of fumarate hydratase (FH) predispose patients to an aggressive form of renal cell carcinoma (RCC). Since other than tumor resection there is no effective therapy for metastatic FH-deficient RCC, an accurate method for early diagnosis is needed. Although MRI or CT scans are offered, they cannot differentiate FH-deficient tumors from other RCCs. Therefore, finding noninvasive plasma biomarkers suitable for rapid diagnosis, screening, and surveillance would improve clinical outcomes. Taking advantage of the robust metabolic rewiring that occurs in FH-deficient cells, we performed plasma metabolomics analysis and identified 2 tumor-derived metabolites, succinyl-adenosine and succinic-cysteine, as excellent plasma biomarkers for early diagnosis. These 2 molecules reliably reflected the FH mutation status and tumor mass. We further identified the enzymatic cooperativity by which these biomarkers are produced within the tumor microenvironment. Longitudinal monitoring of patients demonstrated that these circulating biomarkers can be used for reporting on treatment efficacy and identifying recurrent or metastatic tumors.

Adenosine A2A Receptor Mediates Inhibition of Synovitis and Osteoclastogenesis after Electroacupuncture in Rats with Collagen-Induced Arthritis.

BACKGROUND: This study was to investigate the role of adenosine A2A receptors (A2AR) in inhibiting the effect of electroacupuncture (EA) on osteoclastogenesis in collagen-induced arthritis (CIA). METHODS: Wistar rats were divided into four groups: sham-control group, CIA-control group, CIA-EA group, and CIA-EA-SCH58261 (A2AR antagonist) group. We detected tumor necrosis factor-α (TNF-α), nuclear transcription factor-κB (NF-κB), receptor activator of NF-κB ligand (RANKL), protein kinase A (PKA), and extracellular regulatory protein kinase 1/2 (ERK1/2) in peripheral blood by ELISA. PKA, ERK1/2, and NF-κB in ankle joints were determined by western blotting. We evaluated the arthritis damage by histological examination and determined the number of osteoclasts by tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: EA treatment downregulated the expression of TNF-α, RANKL, PKA, ERK1/2, and NF-κB in peripheral blood but increased the levels of PKA and ERK1/2 in ankle joints. Importantly, EA treatment reduced bone erosion as evidenced by the histological findings and inhibited osteoclastogenesis as revealed by TRAP staining. All these effects of the EA treatment were reversed by combining EA treatment with the A2AR antagonist SCH58261. CONCLUSION: Our data suggest that EA treatment activated A2AR. The effects of the A2AR antagonist SCH58261 suggest that the inhibition of osteoclast formation, the inhibition of TNF-α, RANKL, and NF-κB expression, and the increase of ERK1/2 are all dependent on this EA-induced A2AR activation. It is therefore likely that these pathways with clearly defined roles in inflammation and bone erosion are at least partially involved in the mediation of the inhibition of synovitis and osteoclast formation induced by EA.

The value of blood oxygenation level-dependent (BOLD) MR imaging in differentiation of renal solid mass and grading of renal cell carcinoma (RCC): analysis based on the largest cross-sectional area versus the entire whole tumour.

OBJECTIVES: To study the value of assessing renal masses using different methods in parameter approaches and to determine whether BOLD MRI is helpful in differentiating RCC from benign renal masses, differentiating clear-cell RCC from renal masses other than clear-cell RCC and determining the tumour grade. METHODS: Ninety-five patients with 139 renal masses (93 malignant and 46 benign) who underwent abdominal BOLD MRI were enrolled. R2* values were derived from the largest cross-section (R2*largest) and from the whole tumour (R2*whole). Intra-observer and inter-observer agreements were analysed based on two measurements by the same observer and the first measurement from each observer, respectively, and these agreements are reported with intra-class correlation coefficients and 95% confidence intervals. The diagnostic value of the R2* value in the evaluation was assessed with receiver-operating characteristic analysis. RESULTS: The intra-observer agreement was very good for R2*largest and R2*whole (all > 0.8). The inter-observer agreement of R2*whole (0.75, 95% confidence interval: 0.69~0.79) was good and was significantly improved compared with the R2*largest (0.61, 95% confidence interval: 0.52~0.68), as there was no overlap in the 95% confidence interval of the intra-class correlation coefficients. The diagnostic value in differentiating renal cell carcinoma from benign lesions with R2*whole (AUC=0.79/0.78[observer1/observer2]) and R2*largest (AUC=0.75[observer1]) was good and significantly higher (p=0.01 for R2*largest[observer2] vs R2*whole[observer2], p<0.01 for R2*whole[observer1] vs R2*largest[observer2]) than R2*largest for observer 2 (AUC=0.64). For the grading of clear-cell RCC, both R2*whole and R2*largest were good (all > 0.7) and were not significantly different (p=0.89/0.93 for R2*largest vs R2*whole[observer1/observer2], 0.96 for R2*whole[observer1] vs R2*largest[observer2] and 0.96 for R2*whole [observer2] vs R2*largest[observer1]). CONCLUSIONS: BOLD MRI could provide a feasible parameter for differentiating renal cell carcinoma from benign renal masses and for predicting clear-cell renal cell carcinoma grading. Compared with the largest cross-section, assessing the whole tumour provides better inter-observer agreement in parameter measurement for differentiating renal cell carcinoma from benign renal masses.

Comparison of computed tomographic urography, magnetic resonance urography and the combination of diffusion weighted imaging in diagnosis of upper urinary tract cancer.

PURPOSE: To evaluate the performance of computed tomographic urography (CTU), static-fluid magnetic resonance urography (static-fluid MRU) and combinations of CTU, static-fluid MRU and diffusion weighted imaging (DWI) in the diagnosis of upper urinary tract cancer. MATERIAL AND METHODS: Between January 2010 and June 2011, patients with suspected UUT cancer underwent CTU, static-fluid MRU and DWI (b=1000s/mm(2)) within a 1-week period. The diagnostic performances of CTU, static-fluid MRU and combinations of CTU, static-fluid MRU and DWI for upper urinary tract cancer were prospectively evaluated. The ureteroscopic and histopathologic findings were compared with the imaging findings. RESULTS: Compared to static-fluid MRU alone (sensitivity: 76/75%, reader 1/reader 2), combining DWI with MRI can increase the sensitivity (sensitivity: 84/84%, p=0.031/p=0.016) of upper urinary tract cancer diagnosis. CTU had greater sensitivity (95/94%) and accuracy (92/91%) than both static-fluid MRU (sensitivity: p<0.001/p<0.001 and accuracy: 83/81%, p=0.001/p<0.001) and static-fluid MRU with DWI (sensitivity: p=0.023/p=0.039 and accuracy: 87/85%, p=0.042/p=0.049) for the diagnosis of upper urinary tract cancers. Compared with CTU alone, CTU with DWI did not significantly increase sensitivity, specificity or accuracy. However, the diagnostic confidence was improved when the combined technique was used (p=0.031/p=0.024). Moreover, there was no significant change in sensitivity, specificity, accuracy or diagnostic confidence when static-fluid MRU was used in combination with CTU and DWI. CONCLUSION: Although there is a potential role for static-fluid MRU and static-fluid MRU with DWI in urinary tract imaging, CTU is still the better choice for the diagnosis of upper urinary tract cancer. Combining DWI with CTU can help improve confidence in upper urinary tract cancer diagnoses.

Evaluation of clinical outcomes of antiangiogenic-targeted therapy in patients with pulmonary metastatic renal cell carcinoma using non-contrast-enhanced computed tomography.

RATIONALE AND OBJECTIVES: The objective of this study was to assess whether changes to radiographic parameters before and after treatment with antiangiogenic drugs would improve performance in predicting tumor response with non-contrast-enhanced computed tomography (NCECT) compared to Response Evaluation Criteria in Solid Tumors (RECIST). MATERIAL AND METHODS: The exploration sample group and the validation sample group consisted of 58 and 25 patients, respectively, who had pulmonary metastatic renal cell carcinoma and were receiving antiangiogenic drugs. All patients underwent NCECT scans at baseline and at first evaluation (after two cycles of treatment) with the same scan protocol. Tumor diameter, attenuation value, entropy, and uniformity of the exploration sample group were examined by receiver operating characteristic (ROC) analysis and stepwise discriminant analysis. The threshold value derived from ROC analysis and discriminant function of the exploration sample group were also used for the validation sample group and were compared to RECIST using Kaplan-Meier survival curves. RESULTS: According to the model obtained from the exploration group, Kaplan-Meier curves for patients without disease progression were significantly different for the discriminant analysis of the validation sample group (P = .04) and better than individually using RECIST (P = .08), percentage change for attenuation value (P = .49), entropy (P = .47, .89, .72, .73, and .58), and uniformity (P = .53, .72, .51, .39, and .16; without filtration, at scale values of 1.0, 1.5, 2.0, and 2.5, respectively). CONCLUSIONS: Combined with changes to imaging parameters, including size, attenuation value, and uniformity between pre- and post-treatment, discrimination analysis can help predict biologic response to antiangiogenic drugs and provide a more accurate response assessment than RECIST criteria.