1. Quantification and monitoring of inflammation in murine inflammatory bowel disease with targeted contrast-enhanced US.
- Author
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Deshpande N, Lutz AM, Ren Y, Foygel K, Tian L, Schneider M, Pai R, Pasricha PJ, and Willmann JK
- Subjects
- Animals, Antibodies, Monoclonal pharmacology, Cells, Cultured, Contrast Media, Flow Cytometry, Fluorescent Antibody Technique, Image Interpretation, Computer-Assisted, Inflammation diagnostic imaging, Inflammatory Bowel Diseases drug therapy, Inflammatory Bowel Diseases immunology, Infliximab, Mice, Microbubbles, Poisson Distribution, Ultrasonography, Inflammatory Bowel Diseases diagnostic imaging, P-Selectin metabolism
- Abstract
Purpose: To evaluate ultrasonography (US) by using contrast agent microbubbles (MBs) targeted to P-selectin (MB(P-selectin)) to quantify P-selectin expression levels in inflamed tissue and to monitor response to therapy in a murine model of chemically induced inflammatory bowel disease (IBD)., Materials and Methods: All procedures in which laboratory animals were used were approved by the institutional administrative panel on laboratory animal care. Binding affinity and specificity of MB(P-selectin) were tested in cell culture experiments under flow shear stress conditions and compared with control MBs (MB(Control)). In vivo binding specificity of MB(P-selectin) to P-selectin was tested in mice with trinitrobenzenesulfonic acid-induced colitis (n = 22) and control mice (n = 10). Monitoring of anti-tumor necrosis factor α antibody therapy was performed over 5 days in an additional 30 mice with colitis by using P-selectin-targeted US imaging, by measuring bowel wall thickness and perfusion, and by using a clinical disease activity index score. In vivo targeted contrast material-enhanced US signal was quantitatively correlated with ex vivo expression levels of P-selectin as assessed by quantitative immunofluorescence., Results: Attachment of MB(P-selectin) to endothelial cells was significantly (P = .0001) higher than attachment of MB(Control) and significantly (ρ = 0.83, P = .04) correlated with expression levels of P-selectin on endothelial cells. In vivo US signal in mice with colitis was significantly higher (P = .0001) with MB(P-selectin) than with MB(Control). In treated mice, in vivo US signal decreased significantly (P = .0001) compared with that in nontreated mice and correlated well with ex vivo P-selectin expression levels (ρ = 0.69; P = .04). Colonic wall thickness (P ≥ .06), bowel wall perfusion (P ≥ .85), and clinical disease activity scoring (P ≥ .06) were not significantly different between treated and nontreated mice at any time., Conclusion: Targeted contrast-enhanced US imaging enables noninvasive in vivo quantification and monitoring of P-selectin expression in inflammation in murine IBD., (© RSNA, 2011.)
- Published
- 2012
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