Microscopic Examination of the Sonothrombolysis Process Inside the Transparent to Ultrasound Parallel Plate Flow Chamber

摘要

Parallel plate flow chambers are widely used for cell research in conditions of constant or pulsatile liquid flow. They are also used to analyze the formation of thrombi. The authors designed a flow chamber that is transparent to ultrasound, thus enabling the microscopic observation of the thrombus dissolution process by interaction of drug, microbubbles and ultrasound in real time, in-vitro. Sonothrombolysis was performed at 1 MHz and 3.3 MHz ultrasound frequencies, at space-averaged and time-averaged intensities I_SATA of 0.2-1.6 W/cm^{2. 1 mm thick slices of the human blood clots were exposed to ultrasound in the presence of the Actilyse tissue plasminogen activator at a concentration of 10 μg/ml flowing around the sample. Next, the effect of SonoVue microbubbles at a concentration of 5x105/ml on the dissolution of the thrombus was investigated. Thrombus size changes were observed under a 4x magnification microscope and were recorded as a function of time. The best result was achieved for the Actilyse tissue plasminogen activator at the 1 MHz and 1.6 W/cm2I_SATA, the thrombus was sonolysed within 5.5 minutes. The noticeable effect of the Sono Vue microbubbles on the thrombolysis process appeared at 3.3 MHz, the thrombus was sonolysed in 12 min at I_SATA = 1.6 W/cm2.}