title: Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent.
abstract: OBJECTIVE
  To evaluate the feasibility and reproducibility of ultrasonography (US) performed with dual-selectin-targeted contrast agent microbubbles (MBs) for assessment of inflammation in a porcine acute terminal ileitis model, with histologic findings as a reference standard.
  
  
  METHODS
  The study had institutional Animal Care and Use Committee approval. Acute terminal ileitis was established in 19 pigs; four pigs served as control pigs. The ileum was imaged with clinical-grade dual P- and E-selectin-targeted MBs (MBSelectin) at increasing doses (0.5, 1.0, 2.5, 5.0, 10, and 20 × 10(8) MB per kilogram of body weight) and with control nontargeted MBs (MBControl). For reproducibility testing, examinations were repeated twice after the MBSelectin and MBControl injections. After imaging, scanned ileal segments were analyzed ex vivo both for inflammation grade (by using hematoxylin-eosin staining) and for expression of selectins (by using quantitative immunofluorescence analysis). Statistical analysis was performed by using the t test, intraclass correlation coefficients (ICCs), and Spearman correlation analysis.
  
  
  RESULTS
  Imaging signal increased linearly (P < .001) between a dose of 0.5 and a dose of 5.0 × 10(8) MB/kg and plateaued between a dose of 10 and a dose of 20 × 10(8) MB/kg. Imaging signals were reproducible (ICC = 0.70), and administration of MBSelectin in acute ileitis resulted in a significantly higher (P < .001) imaging signal compared with that in control ileum and MBControl. Ex vivo histologic grades of inflammation correlated well with in vivo US signal (ρ = 0.79), and expression levels of both P-selectin (37.4% ± 14.7 [standard deviation] of vessels positive; P < .001) and E-selectin (31.2% ± 25.7) in vessels in the bowel wall of segments with ileitis were higher than in control ileum (5.1% ± 3.7 for P-selectin and 4.8% ± 2.3 for E-selectin).
  
  
  CONCLUSIONS
  Quantitative measurements of inflammation obtained by using dual-selectin-targeted US are reproducible and correlate well with the extent of inflammation at histologic examination in a porcine acute ileitis model as a next step toward clinical translation.
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621 (H.W., S.M., A.M.L., J.K.W.); Department of Comparative Medicine (S.A.F., R.L.) and Department of Health, Research and Policy (L.T.), Stanford University, Stanford, Calif; Ultrasound Business Unit, Siemens Healthcare, Mountain View, Calif (I.G.); and Bracco Suisse, Geneva, Switzerland (T.B.).
authors.forename: Huaijun
authors.initials: H
authors.lastname: Wang
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621 (H.W., S.M., A.M.L., J.K.W.); Department of Comparative Medicine (S.A.F., R.L.) and Department of Health, Research and Policy (L.T.), Stanford University, Stanford, Calif; Ultrasound Business Unit, Siemens Healthcare, Mountain View, Calif (I.G.); and Bracco Suisse, Geneva, Switzerland (T.B.).
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Felt
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621 (H.W., S.M., A.M.L., J.K.W.); Department of Comparative Medicine (S.A.F., R.L.) and Department of Health, Research and Policy (L.T.), Stanford University, Stanford, Calif; Ultrasound Business Unit, Siemens Healthcare, Mountain View, Calif (I.G.); and Bracco Suisse, Geneva, Switzerland (T.B.).
authors.forename: Steven
authors.initials: S
authors.lastname: Machtaler
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621 (H.W., S.M., A.M.L., J.K.W.); Department of Comparative Medicine (S.A.F., R.L.) and Department of Health, Research and Policy (L.T.), Stanford University, Stanford, Calif; Ultrasound Business Unit, Siemens Healthcare, Mountain View, Calif (I.G.); and Bracco Suisse, Geneva, Switzerland (T.B.).
authors.forename: Ismayil
authors.initials: I
authors.lastname: Guracar
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621 (H.W., S.M., A.M.L., J.K.W.); Department of Comparative Medicine (S.A.F., R.L.) and Department of Health, Research and Policy (L.T.), Stanford University, Stanford, Calif; Ultrasound Business Unit, Siemens Healthcare, Mountain View, Calif (I.G.); and Bracco Suisse, Geneva, Switzerland (T.B.).
authors.forename: Richard
authors.initials: R
authors.lastname: Luong
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621 (H.W., S.M., A.M.L., J.K.W.); Department of Comparative Medicine (S.A.F., R.L.) and Department of Health, Research and Policy (L.T.), Stanford University, Stanford, Calif; Ultrasound Business Unit, Siemens Healthcare, Mountain View, Calif (I.G.); and Bracco Suisse, Geneva, Switzerland (T.B.).
authors.forename: Thierry
authors.initials: T
authors.lastname: Bettinger
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621 (H.W., S.M., A.M.L., J.K.W.); Department of Comparative Medicine (S.A.F., R.L.) and Department of Health, Research and Policy (L.T.), Stanford University, Stanford, Calif; Ultrasound Business Unit, Siemens Healthcare, Mountain View, Calif (I.G.); and Bracco Suisse, Geneva, Switzerland (T.B.).
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621 (H.W., S.M., A.M.L., J.K.W.); Department of Comparative Medicine (S.A.F., R.L.) and Department of Health, Research and Policy (L.T.), Stanford University, Stanford, Calif; Ultrasound Business Unit, Siemens Healthcare, Mountain View, Calif (I.G.); and Bracco Suisse, Geneva, Switzerland (T.B.).
authors.forename: Amelie M
authors.initials: AM
authors.lastname: Lutz
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621 (H.W., S.M., A.M.L., J.K.W.); Department of Comparative Medicine (S.A.F., R.L.) and Department of Health, Research and Policy (L.T.), Stanford University, Stanford, Calif; Ultrasound Business Unit, Siemens Healthcare, Mountain View, Calif (I.G.); and Bracco Suisse, Geneva, Switzerland (T.B.).
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Willmann
mesh_terms: D000208:Acute Disease; D000818:Animals; D003287:Contrast Media; D003424:Crohn Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D019040:E-Selectin / Q000032:analysis; D005240:Feasibility Studies; D005260:Female; D045423:Microbubbles; D019007:P-Selectin / Q000032:analysis; D015203:Reproducibility of Results; D013552:Swine; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D019040:E-Selectin; D019007:P-Selectin