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.