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Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
Changes in dynamic contrast-enhanced pharmacokinetic and diffusion-weighted imaging parameters reflect response to
Gauraang Bhatnagar1, Nikolaos Dikaios1, Davide Prezzi1,2
11 Centre for Medical Imaging, University College London, London, UK.
Objective:
To investigate the effect of tumour necrosis factor (TNF)-α antagonists on MRI dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) parameters in Crohn's disease (CD).
Methods:
42 patients with CD (median age 24 years; 22 females) commencing anti-TNF-α therapy with baseline and follow-up (median 51 weeks) 1.5-T MR enterography (MRE) were retrospectively identified. MRE included DCE (n = 20) and/or multi-b-value DWI (n = 17). Slope of enhancement (SoE), maximum enhancement (ME), area under the time-intensity curve (AUC), Ktrans (transfer constant), ve (fractional volume of the extravascular-extracellular space), apparent diffusion coefficient (ADC) and ADCfast/slow were derived from the most inflamed bowel segments. A physician global assessment of disease activity (remission, mild, moderate and severe) at the time of MRE was assigned, and the cohort was divided into responders and non-responders. Data were compared using Mann-Whitney U test and analysis of variance.
Results:
Follow-up Ktrans, ME, SoE, AUC and ADCME changed significantly in clinical responders but not in non-responders, baseline {[median [interquartile range (IQR)]: 0.42 (0.38), 1.24 (0.52), 0.18 (0.17), 17.68 (4.70) and 1.56 mm(2) s(-1) (0.39 mm(2) s(-1)) vs follow-up [median (IQR): 0.15 (0.22), 0.50 (0.54), 0.07 (0.1), 14.73 (2.06) and 2.14 mm(2) s(-1) (0.62 mm(2) s(-1)), for responders, respectively, p = 0.006 to p = 0.037}. SoE was higher and ME and AUC lower for patients in remission than for those with severe activity [mean (standard deviation): 0.55 (0.46), 0.49 (0.28), 14.32 (1.32)] vs [0.32 (0.37), 2.21 (2.43) and 23.05 (13.66), respectively p = 0.017 to 0.033]. ADC was significantly higher for patients in remission [2.34 mm(2) s(-1) (0.67 mm(2) s(-1))] than for those with moderate [1.59 mm(2) s(-1) (0.26 mm(2) s(-1))] (p = 0.005) and severe disease [1.63 mm(2) s(-1) (0.21 mm(2) s(-1))] (p = 0.038).
Conclusion:
DCE and DWI parameters change significantly in responders to TNF-α antagonists and are significantly different according to clinically defined disease activity status.
Advances In Knowledge:
DCE and DWI parameters change significantly in responders to TNF-α antagonists in CD, suggesting an effect on bowel wall vascularity.
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