Quantification and monitoring of inflammation in murine inflammatory bowel disease with targeted contrast-enhanced US

Nirupama Deshpande, Amelie M. Lutz, Ying Ren, Kira Foygel, Lu Tian, Michel Schneider, Reetesh Pai, Pankaj J. Pasricha, Jürgen K. Willmann

Research output: Contribution to journalArticlepeer-review

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 a 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.

Original languageEnglish (US)
Pages (from-to)172-180
Number of pages9
JournalRADIOLOGY
Volume262
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Quantification and monitoring of inflammation in murine inflammatory bowel disease with targeted contrast-enhanced US'. Together they form a unique fingerprint.

Cite this