Top

Molecular Imaging and Biology

Published in:

01-10-2016 | Research Article

Evaluation of Quantitative Imaging Biomarkers in the DSS Colitis Model

Authors: Anne Beltzer, Thomas Kaulisch, Teresa Bluhmki, Tanja Schoenberger, Birgit Stierstorfer, Detlef Stiller

Published in: Molecular Imaging and Biology | Issue 5/2016

Abstract

Purpose

In humans, colonoscopy is the gold standard for the diagnosis of inflammatory changes of the colon wall. Aim of this study was the identification of less invasive imaging biomarkers in the dextran sodium sulfate (DSS) colitis model to provide additional information on transmural changes of the colon wall.

Procedures

Colitis was induced in C57BL/6 mice by administration of 2, 3, and 4 % DSS over a period of 5 days. Colon wall thickness was measured using magnetic resonance imaging (MRI), ultrasound (US), and x-ray computed tomography (CT), gut inflammation by positron emission tomography/CT, and mucosal changes of the colon wall by colonoscopy. Colon samples were examined histologically.

Results

MRI, CT, US, and histological data revealed increased colon wall thickness in DSS-treated mice compared to healthy controls. Elevated 2-deoxy-2[¹⁸F]fluoro-d-glucose uptake and colonoscopy confirmed high inflammatory load in the guts of colitis mice.

Conclusions

The established quantitative imaging readouts offer promising perspectives to develop new compounds and to translate these methods into the clinical setting.

Podolsky DK (1991) Inflammatory bowel disease (1). N Engl J Med 325:928–937CrossRefPubMed

Baumgart DC, Sandborn WJ (2012) Crohn’s disease. Lancet 380:1590–1605CrossRefPubMed

Hommes DW, van Deventer SJ (2004) Endoscopy in inflammatory bowel diseases. Gastroenterology 126:1561–1573CrossRefPubMed

Stange EF, Travis SP, Vermeire S et al (2006) European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. Gut 55(Suppl 1):i1–i15CrossRefPubMedCentral

Panes J, Bouhnik Y, Reinisch W et al (2013) Imaging Techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based consensus guidelines. J Crohns Colitis 7:556–585CrossRefPubMed

Panes J, Bouzas R, Chaparro M et al (2011) Systematic review: the use of ultrasonography, computed tomography and magnetic resonance imaging for the diagnosis, assessment of activity and abdominal complications of Crohn’s disease. Aliment Pharmacol Ther 34:125–145CrossRefPubMed

Horsthuis K, Bipat S, Bennink RJ, Stoker J (2008) Inflammatory bowel disease diagnosed with US, MR, scintigraphy, and CT: meta-analysis of prospective studies. Radiology 247:64–79CrossRefPubMed

Spier BJ, Perlman SB, Reichelderfer M (2009) FDG-PET in inflammatory bowel disease. Q J Nucl Med Mol Imaging 53:64–71PubMed

Spier BJ, Perlman SB, Jaskowiak CJ, Reichelderfer M (2010) PET/CT in the evaluation of inflammatory bowel disease: studies in patients before and after treatment. Mol Imaging Biol 12:85–88CrossRefPubMed

10.

Glaudemans AW, Maccioni F, Mansi L et al (2010) Imaging of cell trafficking in Crohn’s disease. J Cell Physiol 223:562–571PubMed

11.

Okayasu I, Hatakeyama S, Yamada M et al (1990) A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98:694–702CrossRefPubMed

12.

Wirtz S, Neufert C, Weigmann B, Neurath MF (2007) Chemically induced mouse models of intestinal inflammation. Nat Protoc 2:541–546CrossRefPubMed

13.

Breynaert C, Dresselaers T, Perrier C et al (2013) Unique gene expression and MR T2 relaxometry patterns define chronic murine dextran sodium sulphate colitis as a model for connective tissue changes in human Crohn’s disease. PLoS One 8:e68876CrossRefPubMedPubMedCentral

14.

Becker C, Fantini MC, Neurath MF (2006) High resolution colonoscopy in live mice. Nat Protoc 1:2900–2904CrossRef

15.

Flecknell P (2002) Replacement, reduction and refinement. ALTEX 19:73–78PubMed

16.

Rusche B (2003) The 3Rs and animal welfare—conflict or the way forward? ALTEX 20(Suppl 1):63–76PubMed

17.

Leist M, Kadereit S, Schildknecht S (2008) Food for thought… on the real success of 3R approaches. ALTEX 25:17–32PubMed

18.

Maxwell JR, Viney JL (2009) Overview of mouse models of inflammatory bowel disease and their use in drug discovery. Curr Protoc Pharmacol 5:Unit 5.57.1–5.58.19

19.

Hindryckx P, Staelens S, Devisscher L et al (2011) Longitudinal quantification of inflammation in the murine dextran sodium sulfate-induced colitis model using μPET/CT. Inflamm Bowel Dis 17:2058–2064CrossRefPubMed

20.

Dieleman LA, Ridwan BU, Tennyson GS et al (1994) Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice. Gastroenterology 107:1643–1652CrossRefPubMed

21.

Arndt JW, Grootscholten MI, van Hogezand RA et al (1997) Inflammatory bowel disease activity assessment using technetium-99m-HMPAO leukocytes. Dig Dis Sci 42:387–393CrossRefPubMed

22.

Papós M, Nagy F, Láng J, Csernay L (1993) Technetium-99m hexamethylpropylene amine oxime labelled leucocyte scintigraphy in ulcerative colitis and Crohn’s disease. Eur J Nucl Med 20:766–769CrossRefPubMed

23.

Signore A, Chianelli M, Annovazzi A et al (2000) 123I-interleukin-2 scintigraphy for in vivo assessment of intestinal mononuclear cell infiltration in Crohn’s disease. J Nucl Med 41:242–249PubMed

24.

Kadayakkara DK, Ranganathan S, Young WB, Ahrens ET (2012) Assaying macrophage activity in a murine model of inflammatory bowel disease using fluorine-19 MRI. Lab Investig 92:636–645CrossRefPubMedPubMedCentral

25.

Wang H, Machtaler S, Bettinger T et al (2013) Molecular imaging of inflammation in inflammatory bowel disease with a clinically translatable dual-selectin-targeted US contrast agent: comparison with FDG PET/CT in a mouse model. Radiology 267:818–829CrossRefPubMedPubMedCentral

26.

Schürmann GM, Bishop AE, Facer P et al (1995) Increased expression of cell adhesion molecule P-selectin in active inflammatory bowel disease. Gut 36(3):411–418CrossRefPubMedPubMedCentral

27.

Jubeli E, Moine L, Vergnaud-Gauduchon J, Barratt G (2012) E-selectin as a target for drug delivery and molecular imaging. J Control Release 158:194–206CrossRefPubMed

28.

Cummins EP, Seeballuck F, Keely SJ et al (2008) The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis. Gastroenterology 134:156–165CrossRefPubMed

Title: Evaluation of Quantitative Imaging Biomarkers in the DSS Colitis Model
Authors: Anne Beltzer
Thomas Kaulisch
Teresa Bluhmki
Tanja Schoenberger
Birgit Stierstorfer
Detlef Stiller
Publication date: 01-10-2016
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 5/2016
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-016-0937-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Evaluation of Quantitative Imaging Biomarkers in the DSS Colitis Model

Abstract

Purpose

Procedures

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 5/2016

Improvements in PET Image Quality in Time of Flight (TOF) Simultaneous PET/MRI

PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis

Biodistribution and Radiation Dosimetry of the Enterobacteriaceae-Specific Imaging Probe [18F]Fluorodeoxysorbitol Determined by PET/CT in Healthy Human Volunteers

Cellular Uptake and Intra-Organ Biodistribution of Functionalized Silica-Coated Gold Nanorods

Longitudinal Changes in Glucose Metabolism of Denervated Muscle after Complete Peripheral Nerve Injury

Imaging Early Fate of Cancer Stem Cells in Mouse Hindlimbs with Sodium Iodide Symporter Gene and I-124 PET