| Objective To prepare the block copolymer microbubbles encapsulating perflenapent and observe their physical properties and acute toxicities;to assess the changes of parameters derived from time–intensity curve by adjust ultrasound scanner acquisition settings and change bolus volume and velocity;to investigate the stability in vitro and acoustic contrast-enhanced effect in vivo of block copolymer microbubbles comparing with Sono Vue contrast agent.Methods 1.The diblock copolymer microbubbles encapsulating perflenapent were prepared by single emulsification method.Thereafter morphology,distribution and particle size of microbubble were observed under microscope,density of microbubbles was measured by hematocytometer.Tenfold conventional dose microbubbles were intravenously injected,and animal toxicity reactions were record.2.Different contrast bolus volume(6.0×107,3.0×107,1.5×107,0.75×107 bubbles/kg),contrast bolus velocities(0.6,0.2,0.12 ml/sec),mechanical indexes(0.04?0.08? 0.16?0.31),frequencies(8.0?5.5?3.5MHz),different locations of ROI on kidney cortex(superior,central,inferior)contrast-enhanced ultrasonography were performed to explore the variety regularity of time–intensity curve on rabbit kidney.The derived parameters from time-density curves(AT-arriving time,TP-time to peak,MTT-mean transmit time,PI-peak intensity,SLP-slope and AUCarea under the curve)were analyzed.3.Respectively,the dynamical changes of microbubbles densities of diblock copolymer microbubbles and Sono Vue were compared in vitro.After bolus intravenous injection,the derived parameters of rabbit livers and kidneys(AT,TP,MTT,PI,SLP and AUC)were analyzed.Results 1.The prepared microbubbles were smooth in shape with optimal dispersion,with an average size of(3.7±0.4)?m and density of 2.0×109/ml.After tenfold conventional microbubbles intravenous injection all animals survived and no apparente toxicity reaction and weight loss was found.2.AT increased with increasing packing free ratio contrast bolus velocity;TP(FTP)shortened with increasing contrast bolus volume and decreasing frequency(P<0.05);MTT was independent of volume and velocity,but shortened with increasing mechanical index and decreasing frequency(P<0.05);PI and AUC increased with increasing volume and mechanical index and decreasing frequency(P<0.05).There was an apparent decline in AUC when MI was 0.31,STP and DBP were constant when MI was 0.04 or 0.08 or 0.16 and shortened when MI was 0.31(P<0.05).SLP was greatly affected in all conditions of ultrasound contrast.There were no significant differences in derived parameters from different ROI locations on kidney cortex.3.Compared to Sono Vue contrast agent,the block copolymer microbubbles were more stable with density descend by 23.7% left for 24 hour,which was far lower than the Sono Vue(90.0%).6 parameters derived from ultrasound enhanced TIC of rabbits kidney and livers between the polymer contrast agents and Sonovue contrast agents were compared.In kidney,TP and MTT of polymer contrast agents was significantly longer than Sono Vue(P=0.001 and P=0.000,respectively);AUC was significantly greater than Sono Vue(P=0.040)and both AT and PI show no significant difference(P=0.053 and P=0.187,respectively).In liver,MTT of polymer contrast agents was significantly longer than Sono Vue(P= 0.020);TP was longer than Sono Vue but without statistically significant(P= 0.075);PI?AUC was higher than Sono Vue(P=0.021 and P=0.040,respectively);AT show no significant difference(P= 0.968).Conclusion The diblock copolymer microbubbles encapsulating perflenapent could be prepared with proper sizes,stability in vitro and contrast effect in vivo.The findings indicated that the parameters derived from TIC show certain regular changes under different scan settings and various bolus.The duration of copolymer microbubbles in vivo was significantly longer than Sonovue,which might be a new high polymer material as ultrasound contrast agent. |
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