Effects Of Low Intensity Ultrasound Induced Microbubble Cavitation Combined With Hemocaogulase On Laser Thermal Ablation In Rabbit VX2 Liver Tumors

Part1 Hemocoagulase Combined with Low Intensity Ultrasound Induced Microbubble Cavitation for Augmented Ablation in Rabbit Liver MicrovasculatureObjective:We investigated a new method to block blood perfusion of rabbit liver by combining low intensity ultrasound induced microbubble cavitation,which can damage vascular structures,with the antiangiogenic effects of hemocoagulase(HC)atrox.Methods:Rabbits were randomly divided into 5 groups : The treatment groups received MEUC,HC,PEI and MEUC+HC combined,respectively;the control group received saline intravenously via a micropump.The groups were monitored with contrast-enhanced ultrasound(CEUS)at 1 h and at 7 days post treatment.Qontra Xt software was used for quantitative analysis of blood perfusion in the target area and to determine microvascular changes.Light microscopy,transmission electron microscopy and scanning electron microscopy were used to evaluate the therapeutic effects.Result : After administration of MEUC+HC at 1h and 7 days,the values of the time intensity curve—peak signal intensity,regional blood volume,maximum signal intensity,the mean signal intensity—as measured using CEUS,were significantly lower than those in the other treatment groups.The quantity of hepatic tissue ablated,the microvascular rupture score,and the number of microthrombi were significantly higher in the MEUC+HC group than in the other treatment groups.No damage was observed in the surrounding normal tissue.Conclusion : The results suggest that the vascular effects induced by hemocoagulase combined with low intensity ultrasound induced microbubble cavitation can safely and efficiently block blood perfusion of rabbit liver.Part2 Hemocoagulase Combined with Low Intensity Ultrasound Induced Microbubble Cavitation for Augmented Ablation Microvasculature in Rabbit VX2 Liver TumorsObjective:We investigated a new method for combining low intensity ultrasound induced microbubble cavitation with hemocoagulase(HC)atrox.Our goal was to induce embolic effects in the vasculature and combine these with an antiangiogenic treatment strategy.Methods:Fourteen days after rabbits were implanted with a single slice of the liver VX2 tumor,they were randomly divided into 5 groups: A,a control group;B,a group given only an injection of HC;C,a group treated only with ultrasound cavitation(UC);D,a group treated with MEUC;E,a group treated with MEUC+HC.Contrast-enhanced ultrasound(CEUS)was performed before treatment and 1 hour and 7 days post-treatment to measure the tumor size,enhancement,and necrosis range.Qontra Xt software was used to determine the time intensity curve(TIC)of tumor blood perfusion and microvascular changes.At 1 hour and at 7 days after treatment with MEUC+HC,the parameters of the TIC,which included peak value,regional blood volume(RBV),regional blood flow(RBF),and area under the curve value(AUC)and which were measured using CEUS,were significantly lower than those found in the other treatment groups.Results:The MEUC+HC treatment group showed significant growth inhibition relative to the UC,HC,and MEUC treatment groups.No damage was observed in the surrounding normal tissues.Conclusion:These results support the feasibility of reducing the blood perfusion of rabbit VX2 liver tumor using a new method that hemocoagulase combined with low intensity ultrasound induced microbubble cavitation.Part3 Application of Hemocoagulase Combined with Low Intensity Ultrasound Induced Microbubble Cavitation Enhanced Nd: YAG Laser Ablation for Rabbit VX2 Liver TumorsObjective:In this study,we propose and investigate both safety and efficacy method for hemocoagulase combined with low intensity ultrasound induced microbubble cavitation enhanced ultrasound-guided percutaneous laser ablation(PLA)in rabbit VX2 liver tumors.Methods : Forteen days after rabbits were implanted single liver VX2 tumor,were randomly divided into 5 study groups: A,Control group;B,PLA group;C,HC+PLA group;D,MEUC+PLA group;E,MEUC+HC+PLA group.Nd: YAG laser was coupled to a quartz fibreoptic guide(600μm)with a flat tip.The fibre and a thermocouple were placed in the lumen of one Chiba needles(21-G)and these were inserted into the tumor under ultrasound-guidance.The laser was fired for 6 min at 5 W power.Contrast enhanced ultrasound(CEUS)was performed before treatment and 1h,1 day,7 day,14 day post-treatment for the analysis of tumor size,enhancement and necrosis range.Results:Quantitative analysis time intensity curve(TIC)of the tumor blood perfusion and microvascular changes.Tumor ablated volume in MEUC+HC +PLA group grow significantly bigger than PLA group 1-day and 14-day(P<0.01).A substantial significant reduction of blood flow of the tumors as a result of the MEUC+HC+PLA treatments than PLA treatment of Peak,RBV and AUC parameters(P<0.01).Examination of treated tumors demonstrated necrosis in the ablated zones and increasing surrounding fibrous bands in both treatment groups.No damage was observed in the surrounding normal tissues.Conclusion : Our study seems to offer the safely and efficiently technique of hemocoagulase combined with low intensity ultrasound induced microbubble cavitation enhances the efficiency of laser ablation therapy.Meanwhile,it would therefore be well suited to the treatment of tumor were superficially located or near vital structures.