Theranostics 2018; 8(22):6357-6366. doi:10.7150/thno.26013

Research Paper

Contrast-Enhanced µCT for Visualizing and Evaluating Murine Intestinal Inflammation

Dennis Jung1, Rafael Heiss2, Viktoria Kramer1, Oana-Maria Thoma1,5, Adrian P. Regensburger3, Wolfgang Rascher3, Michael Uder2, Markus F Neurath1,4, Ferdinand Knieling1,3*✉, Maximilian J. Waldner1,5*✉

1. Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Hartmannstraße 14, 91052 Erlangen, Germany
2. Department of Radiology, Friedrich-Alexander-University Erlangen-Nuremberg, Maximiliansplatz 3, 91054 Erlangen, Germany
3. Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander-University Erlangen-Nuremberg, Loschgestraße 15, 91054 Erlangen, Germany
4. Ludwig Demling Center of Excellence, Friedrich-Alexander-University Erlangen-Nuremberg, Germany
5. Erlangen Graduate School in Advanced Optical Technologies (SAOT), Friedrich-Alexander-University Erlangen-Nuremberg, Germany
*shared authorship

Abstract

Rationale: To develop a simple and fast protocol for the assessment of acute and chronic experimental intestinal inflammation using contrast-enhanced µCT.

Methods: For the imaging studies, an acute 2% and 3% dextran sodium sulfate (n = 15, female, 8-12 weeks) and a chronic adoptive transfer colitis model (n = 10, female, 8-9 weeks) were established over 9 days or 6 weeks, respectively. Throughout the experiments, longitudinal measurement of murine intestinal wall thickness and time dependent perfusion was performed on a small animal µCT system (90 kV, 160 μA, FOV: 60 mm, scan time: 17 s, image size: 512x512, layer thickness: 118 µm) between 0.5 and 30 min after intravenous bolus injection of an iodine contrast agent. Weight development, small animal endoscopy, and histological ex vivo analysis were compared to contrast-enhanced µCT imaging findings.

Results: Murine intestinal wall thickness was significantly increased in inflamed colons of acute colitis at day 9 in comparison to pre-inflamed state. Perfusion analysis revealed a late contrast enhancement in acute inflamed colons and the renal medulla at day 9 compared to control mice. An increasing intestinal wall thickness was monitored 3, 5 and 6 weeks after on-set of chronic colitis in comparison to controls. A good correlation with endoscopic (r = 0.75, p < 0.0001) and histologic degree of inflammation (r = 0.83, p = 0.04) was found.

Conclusion: Contrast-enhanced µCT is a simple and fast method to assess acute intestinal inflammation and to monitor disease progression in experimental models of chronic colitis. According to our findings, one single contrast-enhanced µCT-scan is a valid non-invasive modality to quantify the degree of inflammation in the entire digestive tract in murine inflammatory models.

Keywords: contrast-enhanced µCT, murine intestinal inflammation, non-invasive detection of intestinal inflammation

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How to cite this article:
Jung D, Heiss R, Kramer V, Thoma OM, Regensburger AP, Rascher W, Uder M, Neurath MF, Knieling F, Waldner MJ. Contrast-Enhanced µCT for Visualizing and Evaluating Murine Intestinal Inflammation. Theranostics 2018; 8(22):6357-6366. doi:10.7150/thno.26013. Available from http://www.thno.org/v08p6357.htm