Visualization of Inflammation in Experimental Colitis by Magnetic Resonance Imaging Using Very Small Superparamagnetic Iron Oxide Particles

Laura Golusda; Anja A Kühl; Malte Lehmann; Katja Dahlke; Susanne Mueller; Philipp Boehm-Sturm; Jessica Saatz; Heike Traub; Joerg Schnorr; Christian Freise; Matthias Taupitz; Karina Biskup; Véronique Blanchard; Oliver Klein; Ingolf Sack; Britta Siegmund; Daniela Paclik

doi:10.3389/fphys.2022.862212

Visualization of Inflammation in Experimental Colitis by Magnetic Resonance Imaging Using Very Small Superparamagnetic Iron Oxide Particles

Front Physiol. 2022 Jul 12:13:862212. doi: 10.3389/fphys.2022.862212. eCollection 2022.

Authors

Laura Golusda^{1

2

3}, Anja A Kühl², Malte Lehmann¹, Katja Dahlke^{1

2}, Susanne Mueller^{4

5}, Philipp Boehm-Sturm^{4

5}, Jessica Saatz⁶, Heike Traub⁶, Joerg Schnorr⁷, Christian Freise⁷, Matthias Taupitz⁷, Karina Biskup⁸, Véronique Blanchard⁸, Oliver Klein⁹, Ingolf Sack⁷, Britta Siegmund¹, Daniela Paclik^{1

2}

Affiliations

¹ Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² iPATH.Berlin, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Department of Biology, Chemistry and Pharmacy, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
⁴ Department of Experimental Neurology and Center for Stroke Research, Campus Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ NeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Campus Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁶ Bundesanstalt für Materialforschung und-prüfung (BAM), Division Inorganic Trace Analysis, Berlin, Germany.
⁷ Department of Radiology-Experimental Radiology, Campus Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁸ Campus Virchow-Klinikum, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁹ BIH-Center for Regenerative Therapies, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Abstract

Inflammatory bowel diseases (IBD) comprise mainly ulcerative colitis (UC) and Crohn´s disease (CD). Both forms present with a chronic inflammation of the (gastro) intestinal tract, which induces excessive changes in the composition of the associated extracellular matrix (ECM). In UC, the inflammation is limited to the colon, whereas it can occur throughout the entire gastrointestinal tract in CD. Tools for early diagnosis of IBD are still very limited and highly invasive and measures for standardized evaluation of structural changes are scarce. To investigate an efficient non-invasive way of diagnosing intestinal inflammation and early changes of the ECM, very small superparamagnetic iron oxide nanoparticles (VSOPs) in magnetic resonance imaging (MRI) were applied in two mouse models of experimental colitis: the dextran sulfate sodium (DSS)-induced colitis and the transfer model of colitis. For further validation of ECM changes and inflammation, tissue sections were analyzed by immunohistochemistry. For in depth ex-vivo investigation of VSOPs localization within the tissue, Europium-doped VSOPs served to visualize the contrast agent by imaging mass cytometry (IMC). VSOPs accumulation in the inflamed colon wall of DSS-induced colitis mice was visualized in T₂* weighted MRI scans. Components of the ECM, especially the hyaluronic acid content, were found to influence VSOPs binding. Using IMC, co-localization of VSOPs with macrophages and endothelial cells in colon tissue was shown. In contrast to the DSS model, colonic inflammation could not be visualized with VSOP-enhanced MRI in transfer colitis. VSOPs present a potential contrast agent for contrast-enhanced MRI to detect intestinal inflammation in mice at an early stage and in a less invasive manner depending on hyaluronic acid content.

Keywords: DSS-induced colitis; extracellular matrix; inflammatory bowel diseases; magnetic resonance imaging; transfer colitis; very small superparamagnetic iron oxide nanoparticles.