Dynamic Intrahepatic Flow and Cellular Alterations during Radiofrequency Ablation of Liver Tissue in Mice

Abstract

The purpose of this study was to identify microvascular and other associated changes that occur in the liver during focal heating with monopolar radiofrequency (RF). Intravital video microscopy was performed on exteriorized transilluminated livers of 15 live mice during RF-induced heating of liver parenchyma. Microvascular flow parameters, flow reversibility, microbubble formation, phagocytic activity, and endothelial permeability were recorded throughout a range of tip temperatures (40 degrees C-95 degrees C). During RF application, five discrete zones extended outward from the electrode surface: (i) tissue coagulation, (ii) cellular edema/necrosis, (iii) sinusoidal stasis, (iv) parenchymal shunting, and (v) normal liver tissue. Reversal of stasis in sinusoids and small (<25 microm) vessels occurred at tip temperatures below 50 degrees C. This zone of stasis corresponded to the hyperemic zone on histologic analysis. Although alterations in permeability and phagocytic activity were first identified at 43 degrees C, tip temperatures higher than 55 degrees C always produced local endothelial leakiness to carbon microparticles at the periphery and always inhibited phagocytic activity. At tip temperatures higher than 95 degrees C, microbubble formation occurred with bubbles ultimately tracking through necrotic tissue into patent sinusoids. Larger peripheral vessels (>30 microm) limited extension of coagulation. Although coagulation occurs at tip temperatures higher than 50 degrees C, RF heating induced reversible microvascular stasis at temperatures lower than 50 degrees C. Increased sinusoidal endothelial permeability occurs at near-coagulative temperatures. Therefore, targeted endovascular microparticle delivery through this leaky endothelium may provide an additional and complimentary adjunct for RF ablation therapy.