Purpose To compare the utility of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) in characterizing fibrosis and chronic hepatitis in patients with chronic liver diseases. MATERIALS AND METHODS Following IRB approval, 76 patients with chronic liver disease underwent abdominal MRI, MRE and DWI. Severities of liver fibrosis and chronic hepatitis were graded by histopathologic analysis according to standard disease-specific classification. The overall predictive ability of MRE and DWI in assessment of fibrosis was compared by constructing a receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC) based on histopathologic analysis. RESULTS Using ROC analysis, MRE showed greater capability than DWI in discriminating stage 2 or greater (≥F2), stage 3 or greater (≥F3), cirrhosis (≥F4) shown as significant differences in AUC (P=0.003, P=0.001, P=0.001, respectively). Higher sensitivity/specificity were demonstrated by MRE in predicting fibrosis scores ≥F2 (91%/97%), scores ≥F3 (92%/95%), and scores F4 (95%/87%) compared to DWI (84%/82%, 88%/76%, and 85%/68%). Although MRE had higher ability in identification of liver with fibrosis scores ≥F1 than DWI, a significant difference was not seen (P=0.398). Stiffness values on MRE increased in relation to increasing severity of fibrosis as confirmed by histopathology scores; however, a consistent relationship between apparent diffusion coefficient (ADC) values and stage of fibrosis was not demonstrated. In addition, liver tissue with chronic hepatitis preceding fibrosis may account for mild elevation of liver stiffness. CONCLUSIONS MRE had greater predictive ability in distinguishing the stages of liver fibrosis compared with DWI.
SUMMARY Local environment may impact the development and function of tissue-resident T regulatory cells (Tregs) that are crucial for controlling inflammation. Although the aryl hydrocarbon receptor (Ahr), an environmental sensor, is expressed by Tregs, its role in Treg cell development and/or function remains elusive. Here, we generated mouse genetic models to ablate or activate Ahr expression specifically in Tregs. We showed that Ahr was expressed more abundantly by peripherally induced Treg (pTregs) in the gut, and its expression was independent of microbiota. Ahr was important for Treg gut homing and function. Ahr inhibited pro-inflammatory cytokines produced by Tregs but was dispensable for Treg stability. Furthermore, Ahr-expressing Tregs had enhanced in vivo suppressive activity compared to Tregs lacking Ahr expression in a T cell transfer model of colitis. Our data suggest that Ahr signaling in Tregs may be important for gut immune homeostasis.
Purpose: To evaluate the utility of diffusion-weighted magnetic resonance imaging (DWI) in pancreatic ductal adenocarcinoma with various grades of differentiation. Materials and Methods:Following Institutional Review Board (IRB) approval, 21 consecutive patients with surgical pathology-proven pancreatic adenocarcinomas were retrospectively evaluated. Histopathologic characteristics and grades of differentiation of adenocarcinomas were analyzed. Twenty-one patients without a known history of pancreatic disease were evaluated as the control group. Anatomic MR images and DW images were acquired using 1.5-T MR systems. DWI with b values of 0 and 500 sec/ mm 2 were performed on both patients and control groups. The difference in mean apparent diffusion coefficient (ADC) values among groups of normal pancreatic parenchyma, adenocarcinomas with poor differentiation, and adenocarcinomas with well/moderate differentiation were compared using one-way analysis of variance.Results: Mean ADCs of pancreatic adenocarcinomas (1.77 6 0.45 Â 10 À3 mm 2 /sec) was not significantly lower than that of normal parenchyma (1.98 6 0.31) (P ¼ 0.09). When adenocarcinomas were subdivided based on grades of differentiation, however, poorly differentiated adenocarcinoma with histopathologic characteristics of limited glandular formation and dense fibrosis had significantly lower ADCs (1.46 6 0.17) compared to those of well/moderately differentiated adenocarcinomas (2.10 6 0.42) characterized by neoplastic tubular structures (P < 0.01). Well/moderately differentiated adenocarcinomas with dense fibrosis showed significantly lower ADC values (1.49 6 0.19) than those with loose fibrosis (2.26 6 0.30) (P ¼ 0.01).Conclusion: Difference in ADC values using DWI between poorly and well/moderately differentiated pancreatic ductal adenocarcinoma may relate to differences in glandular formation and density of fibrosis.
Purpose To compare the diagnostic accuracy of MR elastography and anatomic MR imaging features in the diagnosis of severe hepatic fibrosis and cirrhosis. Materials and Methods Three readers independently assessed presence of morphological changes associated with hepatic fibrosis in 72 patients with liver biopsy including: caudate to right lobe ratios, nodularity, portal venous hypertension (PVH) stigmata, posterior hepatic notch, expanded gallbladder fossa and right hepatic vein caliber. Three readers measured shear stiffness values using quantitative shear stiffness maps (elastograms). Sensitivity, specificity and diagnostic accuracy of stiffness values and each morphological feature were calculated. Inter-reader agreement was summarized using weighted kappa statistics. Intra-class correlation coefficient was used to assess inter-reader reproducibility of stiffness measurements. Binary logistic regression was used to assess inter-reader variability for dichotomized stiffness values and each morphological feature. Results Using 5.9 kPa as a cut-off for differentiating F3–F4 from F0–2 stages, overall sensitivity, specificity and diagnostic accuracy for MR elastography were 85.4%, 88.4 % and 87% respectively. Overall inter-reader agreement for stiffness values was substantial, with insignificant difference (p=0.74) in the frequency of differentiating F3–4 from F0–2 fibrosis. Only hepatic nodularity and PVH stigmata showed moderately high overall accuracy of 69.4% and 72.2%. Inter-reader agreement was substantial only for PVH stigmata, moderate for C/R m, deep notch and expanded gallbladder fossa. Only posterior hepatic notch (p=0.82) showed no significant difference in reader rating. Conclusion MR elastography is a non-invasive, accurate and reproducible technique compared with conventional features of detecting severe hepatic fibrosis.
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