Rongbiao Tang1, Wei-Min Chai2, Fuhua Yan2, Guo-Yuan Yang3, Ke-Min Chen4. 1. Department of Radiology, Shanghai Jiao Tong University School of Medicine, Rui Jin Hospital, Shanghai, 200025, People's Republic of China. tangme8688258@sina.com. 2. Department of Radiology, Shanghai Jiao Tong University School of Medicine, Rui Jin Hospital, Shanghai, 200025, People's Republic of China. 3. Neuroscience and Neuroengineering Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China. 4. Department of Radiology, Shanghai Jiao Tong University School of Medicine, Rui Jin Hospital, Shanghai, 200025, People's Republic of China. keminchenrj@163.com.
Abstract
OBJECTIVES: 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. KEY POINTS: • 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.
OBJECTIVES: 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. KEY POINTS: • 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.
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