title: Quantification and monitoring of inflammation in murine inflammatory bowel disease with targeted contrast-enhanced US.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  Targeted contrast-enhanced US imaging enables noninvasive in vivo quantification and monitoring of P-selectin expression in inflammation in murine IBD.
authors: Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305-5621, USA.
authors: Nirupama
authors: N
authors: Deshpande
authors: Amelie M
authors: AM
authors: Lutz
authors: Ying
authors: Y
authors: Ren
authors: Kira
authors: K
authors: Foygel
authors: Lu
authors: L
authors: Tian
authors: Michel
authors: M
authors: Schneider
authors: Reetesh
authors: R
authors: Pai
authors: Pankaj J
authors: PJ
authors: Pasricha
authors: Jürgen K
authors: JK
authors: Willmann
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002478:Cells, Cultured; D003287:Contrast Media; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007090:Image Interpretation, Computer-Assisted; D007249:Inflammation / Q000000981:diagnostic imaging; D015212:Inflammatory Bowel Diseases / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000276:immunology; D000069285:Infliximab; D051379:Mice; D045423:Microbubbles; D019007:P-Selectin / Q000378:metabolism*; D016012:Poisson Distribution; D014463:Ultrasonography
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; D019007:P-Selectin; D000069285:Infliximab