Huaijun Wang1, Stephen A Felt1, Steven Machtaler1, Ismayil Guracar1, Richard Luong1, Thierry Bettinger1, Lu Tian1, Amelie M Lutz1, Jürgen K Willmann1. 1. 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.).
Abstract
PURPOSE: 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. MATERIALS AND 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). CONCLUSION: 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.
PURPOSE: 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. MATERIALS AND 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). CONCLUSION: 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: M A Labow; C R Norton; J M Rumberger; K M Lombard-Gillooly; D J Shuster; J Hubbard; R Bertko; P A Knaack; R W Terry; M L Harbison Journal: Immunity Date: 1994-11 Impact factor: 31.745
Authors: Huaijun Wang; Stephen A Felt; Ismayil Guracar; Valentina Taviani; Jianhua Zhou; Rosa Maria Silveira Sigrist; Huiping Zhang; Joy Liau; José G Vilches-Moure; Lu Tian; Yamil Saenz; Thierry Bettinger; Brian A Hargreaves; Amelie M Lutz; Jürgen K Willmann Journal: Eur Radiol Date: 2017-11-23 Impact factor: 5.315
Authors: Igor Spivak; Anne Rix; Georg Schmitz; Stanley Fokong; Olga Iranzo; Wiltrud Lederle; Fabian Kiessling Journal: Mol Imaging Biol Date: 2016-04 Impact factor: 3.488
Authors: Huaijun Wang; Jean-Marc Hyvelin; Stephen A Felt; Ismayil Guracar; Jose G Vilches-Moure; Samir Cherkaoui; Thierry Bettinger; Lu Tian; Amelie M Lutz; Jürgen K Willmann Journal: Radiology Date: 2018-07-24 Impact factor: 29.146