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P024. Repeated cycles of DSS inducing a chronically relapsing inflammation: A novel model to study fibrosis using in vivo MRI T2 relaxometry

C. Breynaert1, T. Dresselaers2, J. Cremer1, K. Van Steen3, C. Perrier1, S. Vermeire4, P. Rutgeerts4, J. Ceuppens5, U. Himmelreich2, G. Van Assche4

1Catholic University Leuven, Division of gastroenterology, Leuven, Belgium; 2Catholic University Leuven, Biomedical NMR unit – MoSAIC, Leuven, Belgium; 3Montefiore Institute, System and Modeling Unit, Liège, Belgium; 4University Hospital Gasthuisberg, Department of Gastroenterology, Leuven, Belgium; 5Catholic University Leuven, Experimental immunology, Leuven, Belgium

Background: Most experimental animal models of IBD fail to accurately reflect the chronically relapsing inflammation underlying the complications of human CD. This study investigated whether repeated cycles of DSS adequately reflect the effects of chronic transmural healing compared to the acute murine DSS colitis model with recovery. Transmural µMR imaging with in vivo T2 relaxometry, was used to differentiate transmural changes.

Methods: DSS colitis was induced in 6 week-old C57BL6/J mice: repeated cycles mice (n = 8) received 2 cycles of 7 days of DSS followed by 2 weeks of normal drinking water, and for single cycle with recovery mice (n = 4) 7 days of DSS was followed by a 5 weeks recovery period. Control mice (n = 3) received normal drinking water only. After 6 weeks, all mice were scanned in vivo on a 9.4T MRI system.T2 weighted images and T2 maps of the distal colon were recorded. Histograms of the colon wall were created from T2 maps. After scanning and euthanasia, the distal colon was harvested for histology and qRT-PCR. Collagen deposition was quantified with MSB staining. Statistical analysis on histograms was performed with RandomForest in R followed by MANOVA and Kullback-Leibler (KL) to study the distribution of T2 maps.

Results: Mice with 2 DSS cycles had a significant shorter colon (p < 0.001), higher colon weight (p = 0.001) and higher colon weight/length ratio (p < 0.001) vs 1 cycle mice with recovery and control mice. Although all animals had a normal DAI score, the colon of the 2 cycle group had a significantly higher macroscopic score than the 1 cycle group (p < 0.001). Histology showed a trend towards a higher collagen content in the 2 cycle model compared to the 1 cycle model and a significantly higher value compared to control mice (p = 0.046). No significant difference was observed in TGFβ, IL13, IL13Ra1 and IL13Ra2 expression.TNFα was significantly higher in the 1 cycle model vs 2 cycle model and controls (p = 0.002). The distribution of T2 maps was significantly different in all conditions:2 cycle vs 1 cycle (p = 0.027), 2 cycle vs control (p = 0.001) and 1 cycle vs control (p = 0.001).KL showed clear differences between the distributions of T2 maps of the different conditions.

Conclusions: The chronic repeated cycle DSS model with relapse and remission is clearly different from the acute DSS model with recovery. This model opens perspectives to study the effects of healing and fibrosis in CD. In vivo T2 relaxometry is a promising non-invasive assessment of inflammation and should be explored in CD patients.