title: A simple method for quantifying ultrasound-triggered microbubble destruction.
abstract: Ultrasound-triggered microbubble destruction (UTMD) is essential for targeted drug delivery but currently there is no agreed gold standard for its real-time monitoring. This study used a clinical diagnostic ultrasound scanner to quantify the destruction effects of different values of mechanical index (MI) on microbubble. This was achieved by measuring the signal intensity of peripheral vessels, which is representative of systemic microbubble concentration. Twenty-four male Sprague-Dawley rats and SonoVue contrast agent were used for this study, six for the determination of signal saturation and 18 for the study of microbubble destruction. In the first part of the experiment, four different SonoVue doses (200, 400, 600 and 800 μL/kg) were injected into each of six rats and the signal intensity in their right femoral arteries were recorded using a diagnostic ultrasound scanner. This data was used to plot time-intensity curves (TIC) to determine at which concentration the signal reaches saturation. Then UTMD studies were performed using the 400 μL/kg dose as its peak signal intensity (PSI) was safely within the linear portion of the intensity-concentration curve. The remaining 18 rats were divided into three MI groups (0.2, 0.6 and 1.0) and for each rat, the following was performed: TIC recording of a sham exposure without sonication was performed first using the same scanner from signal saturation study. Simultaneously, another ultrasound scanner was applied to the adductor muscles of left hind limb for sonication later. Then, a sonication TIC recording was performed, with both ultrasound scanners activated. A TIC recording of second sonication was also obtained for comparison. The TICs showed that the area under the curve and the enhancement duration were reduced after sonication in the groups MI = 0.6 and MI = 1.0 but not for the group MI = 0.2. The PSI in the groups with MI of 0.6 and 1.0 were slightly lowered after sonication, although it is not statistically significant. No significant difference of TIC exists between the first and the second sonication for each group. Pharmacokinetic analysis was performed with estimated concentration-time curve derived from TIC curve and found that SonoVue had faster clearance and decreased half-life in the groups MI = 0.6 and MI = 1.0. In conclusion, this study shows that sonographic signal measured from peripheral vessels is a feasible indicator of systemic microbubble concentration and may be used to quantify ultrasound-triggered microbubble destruction at target site.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shuo-Hui
authors.initials: SH
authors.lastname: Hung
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Yeh
authors.forename: Tung-Hu
authors.initials: TH
authors.lastname: Tsai
authors.forename: Tom
authors.initials: T
authors.lastname: Chen
authors.forename: Ran-Chou
authors.initials: RC
authors.lastname: Chen
mesh_terms: D000818:Animals; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D008422:Materials Testing; D045423:Microbubbles; D010743:Phospholipids / Q000737:chemistry* / Q000528:radiation effects*; D011829:Radiation Dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013010:Sonication / Q000379:methods*; D013459:Sulfur Hexafluoride / Q000737:chemistry* / Q000528:radiation effects*; D014463:Ultrasonography / Q000379:methods*
chemical_list: D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride