| High intensity focused ultrasound (HIFU) focused low-energy ultrasound on biological focal region (BFR) in vivo utilized it's penetrability, directionality and focalization, and created transient temperature about 60 to 100 degrees Celsius to cause tissue coagulation necrosis without surrounding tissues injury. As a new non-invasive local therapy technology of solid tumors, HIFU has been widely used in clinical treatment of various tumors. As the ultrasound characteristics, the greater the propagation distance, the greater the ultrasonic energy attenuation, and the lower the energy reached target; if the target tissue was uniform, the acoustic impedance (AI) difference was small, ultrasonic energy would be more difficult to deposit. Therefore, HIFU therapy used high dose and long time to achieve ablation purpose. That was effective, but long time leading to operator fatigue, and high dose leading to injury of skin and surrounding tissue, which increased the insecurity. Acoustic environment in tissue (AET) indicated the acoustic characteristics of target tissue during HIFU therapy, or the ultrasound features showed by the density, structure, function and blood supply of tissue, that were the medium (tissue) factors impacting the deposition of ultrasonic energy. In this study, ultrasonic energy deposition were increased and efficacy of HIFU therapy were enhanced by changing acoustic environment in tissue (CAET) to change the acoustic characteristics.①To explore the feasibility of the establish of rabbit VX2 hepatic tumor model by tumor lump implantation and to study the feature and the biology characteristics of the model, to offer the experimental evidence for the application of the model.②To observe the pathological regression of rabbit VX2 hepatic tumors after low-dose irradiation with focused ultrasound, and to explore the role and mechanism of the irradiation in changing acoustic environment of rabbit VX2 hepatic tumors.③To investigate the efficacy and impact of the twice irradiation on rabbit VX2 hepatic tumors using high intensity focused ultrasound (HIFU), and to offer a new way of HIFU treatment for liver cancer.70 purebred New Zealand rabbits, male or female, were all 1.5 to 2.0 kg by weight,2 to 3 months by age. To establish rabbit VX2 hepatic tumor model by tumor lump implantation.5 of 30 tumor-bearing rabbits selected Randomly were sacrificed to observe the tumor growth and metastasis respectively in 1,2,3,4 and 5 weeks after modeling, then the tumor tissue were observed under light microscope. The spontaneous survival time of the remaining 5 tumor-bearing rabbits were observed.Other 10 tumor-bearing rabbits selected randomly were ablated by HIFU (250 W) 16 days after the tumor implantation, as group A (one-time irradiation group).The remaining 30 tumor-bearing rabbits were irradiated by low-dose focused ultrasound (100 W) 15 days after the tumor implantation.2 tumor-bearing rabbits were sacrificed and the tumor tissue were observed under light and electron microscope 1 (immediately),2,3,5,7 days after the low-dose irradiation with focused ultrasound. The remaining 20 tumor-bearing rabbits were randomly divided into two groups:group B (two-day twice irradiation group), of which rabbits were ablated by HIFU 2 days after the low-dose irradiation; group C (inter-day twice irradiation group), of which rabbits were ablated by HIFU 3 days after the low-dose irradiation. The ablation process were the same with group A.During low-dose irradiation and ablation, the procedure "from lines-to planes; from planes to volume" was followed. The spacing was 3 mm and 8 mm respectively between two nearest planes and between two closest lines, the scan speed of ultrasound beam was set to be 3 mm/s. The treatment time, skin change, energy efficiency factor, pathologic analysis, recurrence and metastasis, and survival time of the 3 groups were compared.Measurement data were presented as mean±standard deviation, while count data as rate; measurement data were statistically analyzed by t test, while count data by x2 test. Test level a= 0.05. Statistic were processed by the Statistical Package SAS 8.1.The tumors could grow up in 2 weeks after implanting. The successful rate of implantation was 100%. Metastases in Liver were appeared 4 weeks after implanting, and lung metastases were appeared in all tumor-bearing rabbits 5 weeks after implanting. Macroscopic observation showed that the tumors were gray white in color and felt harder, necrotic foci was present in the center of the tumor over 2.0 cm in diameter. Light microscope observation showed that the tumor cells were relatively large with abundant cytoplasm and large nucleus, the tumor cells'nucleoplasm proportion was great, and tumor cells arranged irregularly. Electron microscope observation showed that the tumor cells were irregular within less organelles in the cytoplasm, and nucleus were large and abnomal with rich euchromatin in it. Tumor-bearing rabbits' spontaneous survival time was 39 to 57 days. The cause of their death was multiple system organ failure for the large tumor and wide metastasis.Rabbit VX2 hepatic tumor tissue were changed after low-dose focused ultrasound irradiation. Light microscope changes:edema existed in tumor cells after irradiation instantly, congestion and aggravated edema were found at 2 and 3 days later, then the injured cells recovered gradually. Electron microscope changes:detached endothelial cells of hepatic sinusoid and swelling organelles in tumor cells cytoplasm were observed instantly after irradiation, while 2 or 3 days later, erythrocyte aggregation was found in hepatic sinusoid and cavitations were found in cytoplasm. Thereafter, organelles swelling reduced till resumed to normal.The first low-dose irradiation power of twice irradiation group was 2/5 of the ablation power, and twice irradiation group were irradiated twice, so each irradiation time and the dose reduced, but the total treatment time (sum of the first low-dose irradiation time and re-irradiation ablation time) was not extend. After ablation, the tumor tissue of three groups was all typical coagulation necrosis, recurrence and metastasis were effective controlled, but the skin erythema occurring rate and EEF of twice irradiation group was significantly lower than one-time irradiation group (p<0.05). Among them, the total treatment time, skin erythema occurring rate, ablation time and EEF of two-day twice irradiation were the least, which was the most safe and effective.In pathological morphology, growth process, visceral metastasis and pathological regression, rabbit VX2 hepatic tumors are similar to human hepatocarcinoma. It has such characteristics as short growth period, high success rate and so on. The model is an ideal animal hepatoma model.Low-dose focused ultrasound irradiation can make a series of pathophysiological changes in rabbit VX2 hepatic tumors to change the acoustic environment, and to enhance the efficacy of HIFU re-irradiation to ablate. The acoustic characteristics shown were related to the degree of pathophysiological changes.With the same effect, twice irradiation group have less irradiation time and dose, of which the complications are reduced, and the damage efficiency are enhanced. Among twice irradiation, the way of continuous two-day is the most safe and effective, which would be a new method of HIFU treatment.
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