title: Molecular evaluation of thrombosis using X-ray phase contrast imaging with microbubbles targeted to P-selectin in mice.
abstract: OBJECTIVE
  X-ray phase contrast imaging (PCI) provides excellent image contrast by utilizing the phase shift. The introduction of microbubbles into tissues can cause a phase shift to make microbubbles visibly identified on PCI. In this study, we assessed the feasibility of targeted microbubble-based PCI for the detection of thrombosis.
  
  
  METHODS
  The absorption and phase contrast images of P-selectin-targeted microbubbles (MBP) were obtained and compared in vitro. MBP, control IgG-targeted microbubbles (MBC), and unbound microbubbles (MBU) were tested for binding specificity on thrombi expressing P-selectin. MBP were used as molecular PCI probes to evaluate P-selectin expression in a mouse model of arteriovenous shunt thrombosis that was created using PE tubes in the bypass outside of the mouse body.
  
  
  RESULTS
  PCI clearly showed the microbubbles not viewable via absorption contrast imaging (ACI). In vitro attachment of MBP (91.60 ± 11.63) to thrombi was significantly higher than attachment of MBC (17.80 ± 4.02, P < 0.001) or MBU (9.80 ± 2.59, P < 0.001). In the mouse model of arteriovenous shunt thrombosis, the binding affinity of MBP (15.50 ± 6.25) was significantly greater than that of MBC (0.50 ± 0.84, P < 0.001) or MBU (0.33 ± 0.52, P < 0.001).
  
  
  CONCLUSIONS
  Our results indicate that molecular PCI may be considered as a novel and promising imaging modality for the investigation of thrombosis.
  
  
  CONCLUSIONS
  • Small thrombi are rarely detected by conventional radiography. • Phase contrast imaging (PCI) provides higher contrast and spatial resolution than conventional radiography. • P-selectin targeted microbubbles detected by PCI may suggest early thrombosis.
authors.affiliation: Department of Radiology, Shanghai Jiao Tong University School of Medicine, Rui Jin Hospital, Shanghai, 200025, People's Republic of China. tangme8688258@sina.com.
authors.forename: Rongbiao
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Radiology, Shanghai Jiao Tong University School of Medicine, Rui Jin Hospital, Shanghai, 200025, People's Republic of China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chai
authors.affiliation: Department of Radiology, Shanghai Jiao Tong University School of Medicine, Rui Jin Hospital, Shanghai, 200025, People's Republic of China.
authors.forename: Fuhua
authors.initials: F
authors.lastname: Yan
authors.affiliation: Neuroscience and Neuroengineering Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China.
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
authors.affiliation: Department of Radiology, Shanghai Jiao Tong University School of Medicine, Rui Jin Hospital, Shanghai, 200025, People's Republic of China. keminchenrj@163.com.
authors.forename: Ke-Min
authors.initials: KM
authors.lastname: Chen
mesh_terms: D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D005240:Feasibility Studies; D007089:Image Enhancement / Q000379:methods*; D066298:In Vitro Techniques; D051379:Mice; D045423:Microbubbles; D057054:Molecular Imaging / Q000379:methods; D019007:P-Selectin; D015203:Reproducibility of Results; D013927:Thrombosis / Q000000981:diagnostic imaging*; D014056:Tomography, X-Ray / Q000379:methods*
chemical_list: D003287:Contrast Media; D019007:P-Selectin
keywords: Microbubbles; P-selectin; Phase contrast imaging; Synchrotron radiation; Thrombosis