To explore the effect of low intensity ultrasound (LUS) and microbubble enhanced ultrasound cavitation (MEUS), alone or in combination, on ethanol ablation (EA) of rabbit liver and observe the changes of liver perfusion and liver function.

Sixty-two healthy New Zealand rabbits were randomized to five groups: LUS group (n=6), EA group (n=14), LUS+ EA group (n=14), MEUS+ EA group (n=14), MEUS+ LUS+ EA group (n=14). For LUS, pulsed low intensity focused ultrasound emission was adopted (focal distance, 15 cm; duty cycle, 0.036%-0.22%; therapy duration, 5-6 min). According to the experiment design, surgically exposed left lobe of the liver was treated. In the LUS, MEUS+ EA, and MEUS+ LUS+ EA groups, quantitative parameters were calculated and compared between the experimental and control liver lobes after different treatments. Three rabbits in each of the EA, LUS+ EA, MEUS+ EA, and MEUS+ LUS+ EA groups were used to detect the contents of alanine aminotransferase (ALT) and aspartate transaminase (AST) in arterial blood at five different time points (before treatment, 1 h, 48 h, 5 d, and 7 d after treatment). The livers of the remaining rabbits were harvested for measurement of ethanol ablation volume by drainage method or examination of the histological changes by HE staining 48 h after treatment.

In the LUS group, the peak intensity (PI) and the area under the curve (AUC) were higher in the experiment lobe than in the control lobe, but there was no significant difference. In the MEUS+ EA and MEUS+ LUS+ EA groups, the PI and AUC values were significantly lower in the experiment lobe than in the control lobe (PI: 51.65±16.90 vs 101.09±14.41, 44.08±8.46 vs 113.40±9.35; AUC: 2183.06±501.13 vs 4258.54±841.21, 1900.39±352.59 vs 4385.55±1198.16; t=9.059, 16.835, 9.630, 7.932, P<0.001 for all). In the LUS group, no necrosis was observed, and the necrosis volume was 0 ml. The necrosis volumes caused by ethanol ablation in the EA, LUS+ EA, MEUS+ EA, and MEUS+ LUS+ EA groups were (0.84±0.27) ml, (2.42±1.11) ml, (3.52±1.34) ml, and (4.01±1.45) ml. The ethanol ablation volume was significantly lower in the EA group than in the other three groups (u=-13.800, -20.400, -23.400, P<0.05 for all), although there were no significant difference between any two of the latter three groups. No pathological changes were observed in the ultrasound exposed liver of the LUS group. In contrast, a wide range of coagulation necrosis area was noted in the other four groups. Compared with pre-treatment values, ALT and AST levels in all groups showed a slight rise after treatment, peaked at 48 h, and gradually returned to the pretreatment levels after seven days. The tendency of changes in ALT and AST levels with time was similar among the four groups (F=0.256, P=0.855; F=0.517, P=0.686).

LUS and MEUS, alone or in combination, could significantly increase the ethanol ablated volume of rabbit liver without aggravating liver function.