Predicting and monitoring colitis development in mice by micro-computed tomography.
BACKGROUND
Computed tomography (CT) has been developed as a tool for monitoring human inflammatory bowel disease (IBD). The aim of this study was to evaluate colon wall thickness as a noninvasive marker in the dextran sodium sulfate (DSS) mouse model of colitis using micro-CT.


METHODS
Mice were examined by micro-CT 1, 2, or 4 times between day 0 (d0) and d26 after induction of colitis to document the kinetics of changes in colon wall thickness and its relation to colitis development.


RESULTS
DSS-treated mice displayed a significantly thicker colon wall at all timepoints (days 5, 8, 12, 19, and 26) investigated compared to healthy controls. Colon wall thickness showed a good correlation to the macroscopic grading of colitis (r = 0.81). The increase in colon wall thickness occurred mainly during the acute phase of colitis (between days 5 and 12) and did not progress much further in the chronic phase of colitis (d26). Colon wall thickness at d26 was thereby predicted by measurements at d12. All mice did not respond equally to DSS and this difference was manifest during the first 2 weeks of colitis, providing an important tool in stratifying responders from nonresponders.


CONCLUSIONS
While the potential impact of handling and anesthesia should be considered on repeated micro-CT, irradiation exposure during repeated micro-CT did not affect the development of colitis. Thus, the results suggest that micro-CT can be used for monitoring and prediction of the inflammatory response in mouse colitis in future therapeutic studies.
Fredin
Maria Fritsch
MF
Department of Integrative Pharmacology, AstraZeneca R&D Mölndal, Mölndal, Sweden. maria.fritsch@astrazeneca.com
Hultin
Leif
L
Hyberg
Gina
G
Rehnström
Erika
E
Hultgren Hörnquist
Elisabeth
E
Melgar
Silvia
S
Jansson
Liselotte
L
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000473:pathology; D003106:Colon / Q000000981:diagnostic imaging / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008852:Microradiography; D014057:Tomography, X-Ray Computed
D016264:Dextran Sulfate