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Radiology. 2012 Jan;262(1):172-80. doi: 10.1148/radiol.11110323. Epub 2011 Nov 4.

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

Author information

1
Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305-5621, USA.

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.

PMID:
22056689
PMCID:
PMC3244669
DOI:
10.1148/radiol.11110323
[Indexed for MEDLINE]
Free PMC Article
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