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

Research Paper

Contrast-Enhanced µCT for Visualizing and Evaluating Murine Intestinal Inflammation

Dennis Jung¹, Rafael Heiss², Viktoria Kramer¹, Oana-Maria Thoma^1,5, Adrian P. Regensburger³, Wolfgang Rascher³, Michael Uder², Markus F Neurath^1,4, Ferdinand Knieling^1,3*✉, Maximilian J. Waldner^1,5*✉

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

✉ Corresponding authors: Ferdinand Knieling, MD, Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander-University Erlangen-Nuremberg, Germany, Loschgestraße 15, 91054 Erlangen, Germany. Phone: +49 9131 85-33118; Email: Ferdinand.Knielingde and Maximilian Waldner, MD, Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Germany, Ulmenweg 18, 91054 Erlangen, Germany. Phone: +49 9131 85-35204; Email: Maximilian.Waldnerde More

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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