Micro Bubbles Augmented Sonothrombolysis: An In Vitro And In Vivo Study

Background:It is known that therapeutic ultrasound (US) could accelerate thrombolysis and recanalize vessel possibly by mechanical subdivision like acoustic cavitation. Micro ubbles contrast agent (MB) might enhance US cavitation and potentially augment sonothrombolysis. Although there are many studies about sonothrombolysis both in vitro and in vivo, some influential factors, such as MB coating, some US parameters and pathological mechanism of sonothrombolysis, had not been deeply investigated.Objective:This study was designed to explore some influential factors, effectiveness and mechanism of MB enhanced sonothrombolysis both in vitro and in vivo. In the study, lipid and albumin coated MB, therapeutic US and tissue-plasminogen activator (t-PA) were applied.Methods:In vitro study, whole blood clots (aged 5 h, weighted 200-300 mg) were harvested and prepared from fresh blood of 5 healthy human, perfluorocarbon filled lipid and albumin encapsulated MB, and two US devices at different frequency (20 KHz and 1 MHz) were applied in experiment together with t-PA. The thrombolysis was evaluated by the loss of clots weight in the percentage of baseline weight, termed the thrombolysis ratio. The experiment was grouped in 10 combinations to study the individual factors involved, mainly MB coating, t-PA, US frequencies. Pathology procedure included biological microscopy, electronic microscopy and fluoroscopy. Ultrasonic imaging of clots was performed for echogenicity and tissue homogenicity. 3'3Dioctadecyloxacarbocyanine (DiO) labeled lipid MB was used to trace the MB or the remains around and within clots under...