title: Investigation into the impact of diagnostic ultrasound with microbubbles on the capillary permeability of rat hepatomas.
abstract: Ultrasound-targeted microbubble destruction (UTMD) takes advantage of transiently increased capillary permeability to enhance the release of tumor-specific drugs from blood vessels into sonicated tumor tissues. However, the application of focused ultrasound is limited because of the lack of an appropriate image-monitoring system. In this study, hepatoma-bearing Sprague-Dawley rats were insonicated with low-frequency diagnostic ultrasound and injected with Evans Blue (EB) dye and microbubbles through their tail veins to test changes in capillary permeability. We studied how the mechanical index, sonication duration and the injected microbubble (MB) concentration affect the hepatoma vascular permeability by quantitatively evaluating the EB delivery efficiency. Confocal laser scanning microscopy was used to observe the deposition of red fluorescence-dyed EB in tumor tissues. In addition, P-selectin, a type of biochemical marker that reflects vascular endothelial cell activation, was identified using an immunoblotting analysis. The experimental results reveal that EB delivery efficiency in tumor tissues was greater in groups with the diagnostic ultrasound-mediated UTMD (8.40 ± 0.71 %ID/g) than in groups without UTMD (1.73 ± 0.19 %ID/g) and EB delivery efficiency could be affected by MI, sonication duration and MB dose. The immunoblotting analysis indicates that diagnostic ultrasound-induced UTMD results in the vascular endothelial cell activation to increase capillary permeability, justifying the high quantity of EB deposited in tumor tissues.
authors: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors: Gong
authors: G
authors: Wang
authors: Zhongxiong
authors: Z
authors: Zhuo
authors: Hongmei
authors: H
authors: Xia
authors: Yi
authors: Y
authors: Zhang
authors: Ying
authors: Y
authors: He
authors: Weihua
authors: W
authors: Tan
authors: Yunhua
authors: Y
authors: Gao
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000528:radiation effects*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000503:physiopathology* / Q000628:therapy; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000503:physiopathology* / Q000628:therapy; D045423:Microbubbles / Q000627:therapeutic use; D010743:Phospholipids / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013010:Sonication / Q000379:methods; D013459:Sulfur Hexafluoride / Q000627:therapeutic use; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride