Quantitative diffusion-weighted magnetic resonance enterography in ileal Crohn’s disease: A systematic analysis of intra and interobserver reproducibility

BACKGROUND Magnetic resonance enterography(MRE) is increasingly attractive as a noninvasive and radiation-free tool for assessing Crohn’s disease(CD). Diffusionweighted imaging(DWI) is recommended as an optional MRE sequence for CD by the European Society of Gastrointestinal and Abdominal Radiology, and has shown a superb potential as a quantitative modality for bowel inflammation evaluation. However, the measurement reproducibility of quantitative DWI analysis in MRE has not been ascertained so far. To facilitate the application of quantitative diffusion-weighted MRE in the clinical routine, systematic investigations of the intra and interobserver reproducibility of DWI quantitative parameters should be performed.AIM To evaluate the intra and interobserver reproducibility of quantitative analysis for diffusion-weighted MRE(DW-MRE) in ileal CD.METHODS Forty-four subjects(21 with CD and 23 control subjects) who underwent ileocolonoscopy and DW-MRE(b = 800 s/mm2) within one week were included.Two radiologists independently measured apparent diffusion coefficients(ADC)of the terminal ileum and signal intensity ratio(SR) of the terminal ileum to ipsilateral psoas muscle on DWI images(b = 800 s/mm2). Between-and withinreader agreements were assessed using intraclass correlation coefficients(ICC),coefficients of variation(CoV), and 95% limits of agreement of Bland-Altman plots(BA-LA LoA). Diagnostic performances of ADC and SR for identifying inflamed terminal ileum from the normal were evaluated by receiver operating characteristic(ROC) curve analysis.RESULTS There were no significant differences in ADC or SR values between the two sessions or between the two radiologists either in the CD or control group(paired t-test, P > 0.05). The intra and interobserver reproducibility of ADC(ICC: 0.952-0.984;CoV: 3.73-6.28%;BA-LA LoA: ±11.27% to ±15.88%) and SR(ICC: 0.969-0.989;CoV: 3.51%-4.64%;BA-LA LoA: ±10.62% to ±15.45%) was excellent for CD.Agreement of ADC measurements was slightly less in control subjects(ICC:0.641-0.736;CoV: 10.47%-11.43%;BA-LA LoA: ± 26.59% to ± 30.83%). SR of normal terminal ileum demonstrated high intra and interobserver reproducibility(ICC: 0.944-0.974;CoV: 3.73%-6.28%;BA-LA LoA: ± 18.58% to ± 24.43%). ADC and SR of two readers had outstanding diagnostic efficiencies(area under the ROC curve: 0.923-0.988).CONCLUSION Quantitative parameters derived from DW-MRE have good to excellent intra and interobserver agreements with high diagnostic accuracy, and can serve as robust and efficient quantitative biomarkers for CD evaluation.

Apparent diffusion coefficient-based histogram analysis differentiates histological subtypes of periampullary adenocarcinoma

BACKGROUND For periampullary adenocarcinoma,the histological subtype is a better prognostic predictor than the site of tumor origin.Intestinal-type periampullary adenocarcinoma(IPAC)is reported to have a better prognosis than the pancreatobiliary-type periampullary adenocarcinoma(PPAC).However,the classification of histological subtypes is difficult to determine before surgery.Apparent diffusion coefficient(ADC)histogram analysis is a noninvasive,nonenhanced method with high reproducibility that could help differentiate the two subtypes.AIM To investigate whether volumetric ADC histogram analysis is helpful for distinguishing IPAC from PPAC.METHODS Between January 2015 and October 2018,476 consecutive patients who were suspected of having a periampullary tumor and underwent magnetic resonance imaging(MRI)were reviewed in this retrospective study.Only patients who underwent MRI at 3.0 T with different diffusion-weighted images(b-values=800 and 1000 s/mm^2)and who were confirmed with a periampullary adenocarcinoma were further analyzed.Then,the mean,5th,10th,25th,50th,75th,90th,and 95th percentiles of ADC values and ADCmin,ADCmax,kurtosis,skewness,and entropy were obtained from the volumetric histogram analysis.Comparisons were made by an independent Student's t-test or Mann-Whitney U test.Multiple-class receiver operating characteristic curve analysis was performed to determine and compare the diagnostic value of each significant parameter.RESULTS In total,40 patients with histopathologically confirmed IPAC(n=17)or PPAC(n=23)were enrolled.The mean,5th,25th,50th,75th,90th,and 95th percentiles and ADCmax derived from ADC1000 were significantly lower in the PPAC group than in the IPAC group(P<0.05).However,values derived from ADC800 showed no significant difference between the two groups.The 75th percentile of ADC1000 values achieved the highest area under the curve(AUC)for differentiating IPAC from PPAC(AUC=0.781;sensitivity,91%;specificity,59%;cut-off value,1.50×10^-3 mm^2/s).CONCLUSION Volumetric ADC histogram analysis at a b-value of 1000 s/mm2 might be helpful for differentiating the histological subtypes of periampullary adenocarcinoma before surgery.

ZYZ451 Protects cardiomyocytes from hypoxia-induced apoptosis by enhancing MnSOD and STAT3 interaction

OBJECTIVE 3,5-Dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester(ZYZ451)showed excellent cardio-protective effects in our previous work.However,its therapeutic potential in vivo and the mechanism remained to be elucidated.Herein,we evaluated cardiac protective role of ZYZ451 in post-myocardial infarction(post-MI)rats,and elucidated the underlying mechanism.METHODS Neonatal rat ventricular cardiomyoctys(NRVCs)were separated and subjected to pre-deoxidized(1%O2,5%CO2),and serum-free medium for 4h to obtain ischemic model.Mitochondrial ROS,MnSOD activity and cell apoptosis were tested to verify the cardiac protective effects of ZYZ451.Inhibitors and siRNA for Stat3 were used to determine role of Stat3 played in cardio-protective effectes of ZYZ451.Mitochondria were isolated from NRVCs to determine expression of Stat3 and MnSOD.Immunofluorescence and coimmunoprecipitation were conducted to determine the interaction between MnSOD and Stat3.To apply post-MI model in rats,the rats were subjected to ligation of LAD except for control group.The vehicle or ZYZ451(1,2or 5mg·kg-1)or mixture of Leonurine and SPRC(15mg·kg-1)was administered 7dbefore and 3more days after the operation.Area at risk(AAR),apoptosis in AAR,LDH and MDA levels,and MnSOD activity and expression were detected to evaluate the cardiac injury.Tissue mitochondria were isolated to determine MnSOD and Stat3 expression in ischemia,and coimmunoprecipitaion was performed to verify the interaction between MnSOD and Stat3 in vivo.RESULTS ZYZ451 prevented hypoxia induced NRVCs apoptosis via increasing MnSOD activity and inhibiting mitochondrial ROS production.Interestingly,5,15-DPP(STAT3phosphorylation inhibitor)failed to inhibit MnSOD activity,while knockout of STAT3 resulted in significant reduction of MnSOD activity,followed by increased mitochondrial ROS production and cardiomyocytes apoptosis in hypoxia.Moreover,protective effects of ZYZ451 were blunted in Stat3 deficient NRVCs.These results indicated the necessity of Stat3 on MnSOD activity independent of its transcriptional activity.We further found co-localization of STAT3 and MnSOD by immunofluorescence in NRVCs,coimmunoprecipitation verified their interaction,and ZYZ451 enhanced this interaction.Similar results were found on H9C2 cardiomyoctyes and knockout of STAT3 attenuated the interaction.Consistent with the in vitro results,ZYZ451 reduced myocardial infarct size,cell apoptosis,LDH and MDA content in myocardial infarction rats.The benefits relied on increased MnSOD activity and enhanced STAT3 and MnSOD interaction,as observed in dangerous area of the infracted hearts.CONCLUSION We are the first to report that STAT3 is involved in MnSOD activity regulation,and that ZYZ451 exerts its cardio-protective effects by enhancing MnSOD and STAT3 interaction.These findings indicate a new role for STAT3 beyond as a transcriptional factor and suggest that ZYZ451 is an effective cardioprotective agent.

Assessing the Early Response of Advanced Cervical Cancer to Neoadjuvant Chemotherapy Using Intravoxel Incoherent Motion Diffusion-weighted Magnetic Resonance Imaging： A Pilot Study

Background： Diffusion-weighted imaging （DWI） with the intravoxel incoherent motion （IVIM） model has shown promising results for providing both diffusion and perfusion intbrmation in cervical cancer; however, its use to predict and monitor the efficacy ofneoadjuvant chemotherapy （NACT） in cervical cancer is relatively rare. The study aimed to evaluate the use of DWl with 1VIM and monoexponential models to predict and monitor the efficacy of NACT in cervical cancer. Methods： Forty-two patients with primary cervical cancer underwent magnetic resonance exams at 3 time points （pre-NACT, 3 weeks after the first NACT cycle, and 3 weeks after the second NACT cycle）. The response to treatment was determined according to the response evaluation criteria in solid tumors 3 weeks after the second NACT treatment, and the subjects were classified as two groups： responders and nonresponders groups. The apparent diffusion coefficient （ADC）, true diffusion coefficient （D）, perfusion-related pseudo-diffusion coefficient （D＊）, and perfusion fraction （f） values were determined. The differences in IVlM-derived variables and ADC between the different groups at the different time points were calculated using an independent samples t-test. Results： The D and ADC values were all significantly higher for the responders than tbr the nonresponders at all 3 time points, but no significant differences were observed in the D＊ and fvalues. An analysis of the receiver operating characteristic （ROC） curves indicated that a D value threshold 〈0.93 × 10 3 mm2/s and an ADC threshold 〈1.11× 10 3 mm2/s could differentiate responders from nonresponders at pre-NACT time point, yielding area under the curve （AUC） of which were 0.771 and 0.806, respectively. The ROC indicated that the AUCs of D and ADC at the 3 weeks after the first NACT cycle and 3 weeks after the second NACT cycle were 0.823, 0.763, and 0.787, 0.794, respectively. The AUC values of D and ADC at these 3 time points were not significantly different （P = 0.641, 0.512, and 0.547, respectively）. Conclusions： D and ADC values may be useful for predicting and monitoring the efficacy of NACT in cervical cancer. An IVIM model may be equal to monoexponential model in predicting and monitoring the efficacy of NACT in cervical cancer.