Assessing mucosal inflammation in a DSS-induced colitis mouse model by MR Colonography
Inbal E Biton1, Noa Stettner1, Ayelet Erez2, Alon Harmelin1, and Joel R Garbow3

1Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel, 2Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel, 3Biomedical Magnetic Resonance Laboratory, Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, United States

Synopsis

Inflammatory bowel disease (IBD) is characterized by uncontrolled inflammation of the gastrointestinal tract [1]. Determining the inflammatory state of the colon is critical for defining the disease activity. Endoscopy in human IBD allows visualization of mucosal inflammation [2]. However, the technique is based on grading of the entire colon, which is operator dependent. The mucosa is very fragile, therefore endoscopic evolution is problematic. Therefore, the development of an improved, noninvasive, objective MRI technique may provide a non-invasive assessment tool to depict pathologies in the small intestinal mucosa and, more specifically, along the colon, and to assess the bowel wall and surrounding structures. In this study, dextran sodium sulphate (DSS) polymer treatment was used to induce acute colitis in mice that was subsequently characterized by multi-slice MR colonography.

Purpose

The aim of this study was to develop a non-invasive, objective and quantitative multi-slice MRI technique for detection of mucosal inflammation in a dextran sodium sulfate (DSS)-induced colitis mouse model. The MRI results were validated by comparison with endoscopy and histopathology.

Methods

Animal experiments were approved by the animal care committee. 16 week-old C57BL/6 mice were treated with 1% DSS in the drinking water for 7 days, followed by 5 days of regular water. The mice were scanned at two different time points (days 7 and 11 post DSS treatment onset) using MRI and endoscopy. On the day of sacrifice, colons were removed, and, after their lengths were measured, they were fixed and stained with H&E. Prior to MRI imaging, animals were anesthetized using a mix of Medetomidine/Ketamine. The mouse colon was cleaned using warm water and perfluorinated oil was introduced into the colon via a rectal catheter. MRI experiments were performed on a 9.4T Bruker BioSpec system using a quadrature volume coil with 35-mm inner diameter. T2 maps were acquired using a multi-slice, spin-echo imaging sequence with the following parameters: repetition delay (TR) of 3000 ms, 16 time-echo increments (linearly spaced from 10 to 160 ms), matrix dimension of 256 x 128 and two averages, corresponding to an image acquisition time of 12 min 48 sec. Fourteen continuous slices with slice thickness of 1.0 mm were acquired with a field of view of 3.25 x 2.5 cm2. Quantitative T2-maps were generated from multi-echo, T2-weighted images using an in-house Matlab program. The average T2 of the colon and the colon apparent thickness (CAT) were calculated for each slice. Differences in average T2 and CAT values for each slice and for the mean of the average values across all of the images slices (T2-slices and CAT-slices) were compared using a Student t-Test.

Results

Axial-view T2 maps of colon for representative untreated control mouse and DSS-treated mouse at days 7 and 11 post DSS treatment onset are shown in Figure 1A. Mean T2-slices at days 7 and 11 post DSS treatment onset were significantly higher (p<0.05) than in untreated colons. Mean T2-slices of the untreated control mice (N=6), and DSS-treated mice at day 7 (N=5) and day 11 (N=5) were 61±2, 83±15 and 88±6 ms, respectively. An increase in the mean CAT-slices after DSS treatment was observed at day 11; no significant change was observed on post-treatment day 7. The mean CAT-slices of the untreated control mice, and DSS-treated mice at day 7 and day 11, were 0.51 ± 0.03, 0.49 ± 0.06 and 0.90 ± 0.07 mm, respectively. Analysis of the mean T2 on a slice-by-slice basis along the colon showed that the increase in the mean T2 at day 11 post DSS treatment onset is higher in the distal part of the colon (slice #1) than in the proximal part of the colon (slice #10) [Figure 1B]. At day 7, the increase in the mean T2 was uniform along the colon. Analysis of the CAT on a slice-by-slice basis along the colon showed a significant increase of the thickness at day 11 post DSS treatment, especially in the proximal part of the colon [Figure 1C].

Conclusions

In vivo, quantitative, non-contrast MRI allows quantitative measurement of mucosal inflammation in a DSS-induced colitis mouse model. MRI results were confirmed by in vivo endoscopy and histopathological findings. The MRI technique can be used to detect colon inflammation and increases in the thickness of the intestine wall on a slice-by-slice basis. Most importantly, it can detect colitis severity along the mouse colon.

Acknowledgements

No acknowledgement found.

References

[1] M.I. Torres, A. Rios. World J. Gastroenterol. 2008;14: 1972–1980.

[2] J.E. Slovak, C. Wang et al. The Veterinary Journal. 2015;2013:290-295.

Figures

Figure 1



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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