Purpose: Crohn's disease transmural bowel wall inflammation can lead to fibrosis causing luminal narrowing and fistula which are the main indications to surgery. The aim of our study was to evaluate MR imaging to distinguish submucosal from transmural fibrosis using an original murine model of radiation-induced colitis.
Methods and Materials: Colitis was induced with localised single-dose radiation (27 Gy). We included an inflammation group of 24 rats with pathologic features of severe acute inflammation associated with minimal submucosal fibrosis and a mixed group of 39 rats with pathological features of severe inflammation associated with transmural fibrosis, obtained two and twelve weeks after irradiation, respectively. Fat suppressed T2- and T1-weighted, diffusion-weighted, magnetisation transfer and perfusion using ASL technique 7 T MR imaging was performed.
Results: MR imaging showed significant differences between inflammation and mixed groups in normalised to muscle signal intensity on T2-weighted images (4.2 vs 3.1, P < 0.0001) and T1-weighted images (1.4 vs 1.3, P = 0.0003), ADC (2.17×10-3 vs 1.69×10-3 mm2/s, P < 0.0001), magnetisation transfer ratio (35 vs 42%, P < 0.0001) and perfusion (60 vs 38 mL/min/100g, P = 0.0009). Monoparametric analysis with the best AUC to differentiate the two groups included T2-weighted signal intensity, ADC and magnetisation transfer ratio. The combination with the best global predictive value (94%) included all parameters but T1-weighted parameter (AUC 0.94).
Conclusion: MR multiparametric analysis was able to distinguish transmural from submucosal fibrosis in our radiation-induced model. This model could be used to evaluate antifibrotic treatments currently under development.
Purpose: The diagnosis of the intestinal acute Graft-versus-Host disease (a-GVHD) after allogenic bone marrow transplantation is based on clinical symptoms, CT findings and biopsies. We assessed Magnetic Resonance Imaging (MRI) diagnostic accuracy.
Methods and Materials: We performed a prospective study on 35 patients (range 9-69 years) with clinical suspicion of intestinal a-GvHD, who underwent clinical-endoscopic, histological and multi-parametric MRI evaluation. Inclusion criteria: intestinal symptoms within 100 days from transplantation, <2 weeks between MRI and clinical-endoscopic evaluation. The following MRI features were evaluated: small and large bowel wall thickening, T2 signal and Gadolinium-enhancement of the intestinal wall, mesenteric lymph nodes, peritoneal effusion, comb-sign and restricted diffusion. Histology, clinical-endoscopic data and follow-up were considered as gold standard for diagnosis and staging. Sensibility, specificity, accuracy and Cohen’s kappa were calculated.
Results: In 21/35 (60%) a-GvHD was confirmed at histology and follow-up. In true positive patients, MRI showed significant continuous wall thickening in 76.2%, stratified wall contrast-enhancement in 90%, comb-sign in 76%, increased number of mesenteric lymph nodes in 19%, and free intra-peritoneal fluid in 57.2%. A significant correlation was found between number of pathological intestinal segments and clinical grade of a-GvHD (r=0.54, p=0.009). The distal ileum was the segment most frequently involved (85.7%). MRI sensitivity was 90.5%, specificity 78%, the PPV 86%, NPV 84%, accuracy 85%. Furthermore, MRI detected early disease in 82% of patients without intestinal symptoms.
Conclusion: In patients with intestinal a-GvHD, MRI can diagnose and grade the disease with high accuracy, in both early and more advanced or severe stages.
Purpose: To assess dependence of bowel distention and presence of mannitol in MRE examinations on ADC values.
Methods and Materials: ADC values of small and large bowel walls with high SI in DWI images at b=600 and b=800 grading bowel filling as “distended” and “collapsed” were measured before and after oral ingeston of 2.5% mannitol (1-1.5 l) in 54 patients with no evidence of IBD. ADC differences between bowel filling grades and presence of mannitol were assessed with t-test and Wilcoxon signed-rank test.
Results: Statistically significant differences (p<0.05) were gained in jejunum after preparation where ADC values were lower in wall of collapsed bowel than of distended one (the mean ADC in collapsed bowel at b=600 and b=800 was 1.76×10-3 mm2/s (SD=0.48) and 1.10 (SD 0.32), respectively, whereas in distended bowel at b=600 and b=800 being 2.56×10-3 mm2/s (SD=0.63) and 1.95 (SD 0.41), respectively). Regarding presence of mannitol, higher ADC was achieved in collapsed jejunum for b 600 and 800, respectively, being 1.35 (SD 0.51) and 1.10 (SD 0.32) before preparation, 1.76 (SD 0.51) and 1.47 (SD 0.36) after preparation as well as in distended colon ascendens for ADC 600 and 800, being 1.56 (SD 0.26) and 1.36 (SD 0.27) before preparation and 2.48 (SD 0.59) and 2.10 (SD 0.44) after preparation.
Conclusion: ADC is influenced by both bowel distention degree and presence of mannitol which has to be considered in diagnosis of IBD.
Purpose: To evaluate the role of magnetisation transfer imaging (MTI) for characterisation of intestinal fibrosis compared with contrast-enhanced (CE) imaging and DWI and its capability for differentiating fibrotic from inflammatory strictures in humans with Crohn’s disease (CD).
Methods and Materials: Abdominal MTI, CE and DWI of 31 consecutive CD patients were analysed before elective surgery. Bowel wall MT ratio (MTR) normalised to skeletal muscle, ADC and the percentage of enhancement gain were calculated and region-by-region correlation with surgical specimen was performed for histologic degree of fibrosis and inflammation. The performance of MTI was validated on 5 new patients.
Results: Normalised MTRs correlated with fibrosis scores (r=0.769, P<0.001) but did not correlate with inflammation scores (r=-0.034, P=0.740). Significant differences in normalised MTRs were found among non-fibrotic, mildly, moderately and severely fibrotic walls (all P<0.05). Normalised MTRs of mixed fibrotic and inflammatory bowel walls were significantly higher than that of purely inflammatory bowel walls (P<0.001). High accuracy of normalised MTRs was shown with an AUC of 0.919 (P<0.001) for differentiating moderately-severely fibrotic from non-fibrotic and mildly fibrotic bowel walls, followed by ADC (AUC=0.747, P=0.001) and the percentage of enhancement gain (AUC=0.592, P<0.001). Sensitivity, specificity and AUC of MTI for diagnosing moderate-severe fibrosis in the validation dataset were 80%, 100% and 0.9 (P=0.033), respectively.
Conclusion: MTI outperforms ADC and CE imaging in detecting and distinguishing varying degrees of bowel fibrosis with or without coexisting inflammation. It could potentially be used as a method to differentiate fibrotic from inflammatory intestinal strictures in CD.
Purpose: To assess the best predictors of response to therapy in patients with Crohn’s disease calculated from time - intensity curves after microbubble injection.
Methods and Materials: One-hundred-and-fifteen consecutive patients (66 male and 49 female; 45.76 years ± 11) with a proven diagnosis of Crohn’s disease involving the terminal ileal loop and scheduled to begin or under therapy with corticosteroids or biologics (infliximab or adalimumab) and with stricture of the terminal ileal loop were scanned after sulphur hexafluoride-filled microbubble injection. In each patient the terminal ileal loop was scanned with CEUS before the beginning and at the end of week 6 of pharmacologic treatment. In each patient the percent change (Post - Pre x 100/Pre) of each kinetic parameter - peak enhancement, wash-in and washout rate, mean transit time, area under the whole time-intensity curve (AUC), AUC during wash-in (AUCWI), and AUC during wash-out (AUCWO) were automatically calculated from time intensity curves. Percent changes of responders and non-responders were compared by Mann Whitney test. Separate univariate logistic regressions were conducted to determine the relationship between the percent change of each kinetic parameter (independent variables), and the therapeutic outcome as responder (dependent outcome variable).
Results: Responders (n=72 patients) and non-responders (n=43) differed (P <0.05) in the percent change of peak enhancement, and area under the curve. Percent change of AUC, AUCWI, AUCWO were found predictors of therapeutic outcome.
Conclusion: Area under time-intensity curve obtained after microbubble contrast agent injection is predictor of response to therapy in patients with Crohn’s disease.
Purpose: To explore the performance of PET/MR enterography (PET-MR-E) versus MR enterography (MR-E) alone and PET alone in evaluating active inflammation in Crohn's disease patients.
Methods and Materials: 21 Crohn's disease patients underwent PET/MR-E followed by surgery within 8 weeks, and constitute our study population. The gastrointestinal tract was divided into 5 segments in each patient. Two readers evaluated MR-E alone, PET alone, and PET/MR-E for active inflammation in each segment.
Results: 59/105 bowel segments were positive for active inflammation at surgery. Sensitivity of PET (91.5%) and of PET/MR-E (88%) were statistically significantly higher than MR-E alone (80%) (p = 0.02 and p=0.08, respectively). No statistically significant differences were found between sensitivity of PET and PET/MR-E (p = 0.48). Specificity of MR-E (87%) and PET/MR-E (93%) were statistically significantly higher than PET (74%) (p=0.01 and 0.04, respectively) but no statistically significant difference was found between MR-E and PET/MR-E (p=0.37). Accuracy of PET/MR-E (91%) was statistically significantly higher than PET (84%) and MR-E (83%) (p=0.02 and 0.01, respectively). No statistically significant difference was found between PET and MR-E (p=1.00).
Conclusion: PET/MR-E is significantly more accurate than sub-modality alone and more specific than PET alone in the detection of active inflammation in patients with Crohn's disease.
Purpose: To compare the diagnostic accuracy of magnetic resonance index of activity (MaRIA), Clermont score and PET parameter in detecting ileocolonic inflammation in Crohn’s disease (CD) with an integrated whole-body PET/MR scanner.
Methods and Materials: 50 patients with known CD and recurrent symptoms underwent ileocolonoscopy with biopsy (reference standard) as well as PET/MR enterography. The average time interval between endoscopy and PET/MR scan was 3 days. The endoscopic activity of inflammation was determined by simplified endoscopic activity score for Crohn’s disease (SES-CD) and categorized in absent, mild to moderate and severe (ulcerative inflammation).
Results: A total of 309 ileocolonic segments could be analysed. To detect active inflammatory segments, area under the curve (AUC) of receiver operating characteristic (ROC) for MaRIA was 0.93, sensitivity 0.86 and specificity 0.92 (cutoff ≥ 11.5); for Clermont score 0.89, 0.82 and 0.91 (cutoff ≥ 13); for SUVmax_ratio (SUVmax of the segment divided by SUVmax of liver) 0.87, 0.77 and 0.89 (cutoff ≥ 1.2), respectively. In detecting severe ulcerative inflammatory segments, AUC of ROC for MaRIA was 0.97, sensitivity 1.0 and specificity 0.89 (cutoff ≥ 14); for Clermont score 0.98, 1.0 and 0.93 (cutoff ≥ 17); for SUVmax_ratio 0.95, 0.86 and 0.91 (cutoff ≥ 1.5). MaRIA, Clermont score and SUVmax_ratio all correlated significantly with global SES-CD (rho = 0.76, 0.56 and 0.52, p<0.001).
Conclusion: Both MR parameters were superior to PET in detecting active inflammatory segments. All of the three surrogate markers facilitate high diagnostic accuracy in detecting severe ulcerative inflammation.
Purpose: An accurate and non-invasive technique to identify inflammation or fibrosis predominant strictures in Crohn's disease (CD) patients is crucial for treatment strategy. The aim of this study is to evaluate the value of magnetic transfer imaging as well as conventional MRI in characterizing types of CD strictures, using surgical histopathology as a reference standard.
Methods and Materials: Seventeen CD patients with 56 specimens who had MRI studies within 15 days before surgery were enrolled in this study. MRI findings and variables included MTR, normalized MTR, T2WI high signal intensity, wall thickness, changes of enhancement pattern over time, enhancement pattern and enhancement gain ratio in each phase of the dynamic contrast-enhanced study. Correlation analysis, group difference analysis and logistic regression analysis were performed to find specific MRI variables as predictors for moderate-severe inflammation and fibrosis.
Results: The severity of inflammation was significantly associated with the following MRI variables: T2WI high signal intensity and wall thickness (both P<0.05). The degree of fibrosis was significantly associated with the following MRI variables: MTR, normalized MTR and wall thickness (all P<0.05). Using T2WI high signal intensity as a predictor, MRI is able to differentiate mild and moderate-severe inflammation with a sensitivity of 0.913 and a specificity of 0.800. Using normalized MTR to discriminate mild and moderate-severe fibrosis, the sensitivity and specificity were 0.875 and 0.875, respectively.
Conclusion: T2WI high signal intensity and normalized MTR may serve as MRI markers for predicting moderate-severe inflammation and fibrosis, respectively, which can provide information for clinical treatment options.
Purpose: Magnetic resonance enterography (MRE) is a radiation-free and accurate technique in the assessment of Crohn’s disease, mainly impaired by high costs and prolonged scanning times. Our purpose is to compare the diagnostic performance of standard MRE vs a “fast” protocol consisting of only three sequences.
Methods and Materials: 73 standard MRE examinations of patients with Crohn's disease performed over a 7-month period were retrospectively evaluated. The images of the two protocols were separated and evaluated by two radiologists with 12 and 2 years of experience in MRE. Statistical analysis was performed using the Cohen kappa value, the Lin’s concordance correlation, Bland-Altman plot, and the nonparametric Mann-Whitney U test.
Results: Inter-protocol agreement was excellent for the presence and number of lesions, assessment of intestinal complications, and excellent in recognising inflammation pattern and extra-intestinal complications (kappa value 0.94-0.096). The assessment of fibrosis had lower agreement with a kappa value of 0.84, while an almost perfect concordance (ρc=0.999) was found in the assessment of lesion extension. Inter-observer agreement was excellent for the presence and number of lesions, inflammation and intestinal and extra-intestinal complications; the assessment of fibrosis showed a lower agreement (93%; κ=0.84; 95% CI, 0.69 to 0.96). A concordance coefficient of 0.997 (95% CI 0.995-0.999) between the readers was obtained for the lesion extensions. Moreover, time spent in the evaluation of the fast protocol was significantly lower.
Conclusion: The fast protocol achieves comparable performance with standard MRE. Furthermore, it has potentially enormous benefits in terms of patient’s comfort, time and health-care cost savings.
Purpose: To identify the MRE lesions that persist in patients with Crohn’s disease (CD) in endoscopic remission as indicators of established damage and to determine its relationship with pre-treatment MRE lesions.
Methods and Materials: Patients with CD who had been included in prospective studies on autologous haematopoietic stem cell transplant and/or anti-TNF drugs were evaluated for this study. Inclusion criteria were: presence of at least one segment with severe inflammatory lesions on endoscopy (CDEIS>8.5) or MRE (MaRIA>11) before treatment and achievement of endoscopic remission after 1 year of treatment. Baseline and 1-year MRE were reviewed.
Results: 73 intestinal segments with severe inflammatory lesions from 28 patients achieved endoscopic remission. The prevalence of creeping fat and bowel mural fat did not change in association with achievement of endoscopic remission (p=0.34 and p=0.35, respectively). Furthermore, luminal stenosis persisted in 50% of initial stenosis and mural thickness>3mm remained in 29% of segments. At least one of the aforementioned residual lesions was present in 30/73 segments with endoscopic remission. Regression analysis showed that the predictive factors on MRE for established residual mural lesions after achieving endoscopic remission were the presence of bowel fat deposition (OR=48.3, p=0.001) and stenosis (OR=15.96, p=0.004), whereas creeping fat was the predictive factor for persistent extramural lesions (OR=35.8, p<0.001) and for either mural or extramural lesions (OR=16.25, p<0.001).
Conclusion: Up to 41% of bowel segments in endoscopic long-standing remission after treatment had residual lesions at MRE. The presence of bowel fat deposition, stenosis and creeping fat may predict the development of established damage.
Purpose: The purpose of this study is to evaluate the performance of virtual monochromatic images (VMI) in differentiating diseased and non-diseased bowel segments in Crohn’s disease (CD). The second aim is to compare mural enhancement between patients with and without CD by using VMI.
Methods and Materials: Dual-energy CT enterography (CTE) of 61 patients(47 with CD and 14 without CD) were retrospectively reviewed. Images were reconstructed at VMI energy levels from 40 to 110keV in 10 keV increments. Attenuation, signal-to-noise ratio(SNR), and contrast-to-noise ratio(CNR) were obtained from diseased and non-diseased bowel segments. Subjective analysis of image quality of VMI and polychromatic images(PCI) was performed by two radiologists in consensus. Repeated measures ANOVA and Wilcoxon tests were used in the assessment of quantitative and subjective analyses, respectively.
Results: Attenuation, SNR, and CNR were found to be higher with a statistical significant difference in diseased segments than non-diseased segments in patients with CD at each energy level of VMI. In the evaluation of patients with and without CD, optimal attenuation, SNR, and CNR values were observed at 40keV (area under ROC curve (AUC):0.913;95% confidence interval(CI):0.843-0.984), 40keV (AUC:0.807;95%CI:0.679-0.935), and 70keV (AUC:0.906;95%CI:0.82-0.987), respectively. For subjective analysis, there was a statistically significant difference between the comparison of VMI and PCI (p<0.05).
Conclusion: VMI of dual-energy CTE provide information in differentiating diseased bowel segments in CD by assessing mural enhancement quantitatively. In the evaluation of CD and controls, VMI at 40keV and 70keV allow for the optimal attenuation and CNR of bowel segments, respectively.