Radio-frequency-induced Coagulation Necrosis in Rabbits: Immediate Detection at US with a Synthetic Microsphere Contrast Agent

PURPOSE: To determine whether a synthetic ultrasonographic (US) contrast agent can be used to differentiate coagulation necrosis from untreated tumor immediately after radio-frequency ablative therapy. MATERIALS AND METHODS: VX2 (adenocarcinoma) tumors (0.8-1.5-cm diameter) were implanted into 12 rabbits. Gray-scale and color Doppler US were performed with or without intravenous injection of a US contrast agent composed of poly-lactide-co-glycolic acid polymeric (PLGA) microspheres (2-micron diameter) filled with perfluorocarbon gas. Radio frequency was applied to each nodule for 6 minutes at 127 mA +/- 33 (mean +/- SD) (tip temperature, 92 degrees C +/- 2). Repeat US with a second dose of the contrast agent was performed immediately after ablation. In four animals, a third dose was administered 30-120 minutes after ablation. Radiologic-histopathologic correlation was performed and included in vivo staining and studies of mitochondrial function. RESULTS: Intense contrast agent enhancement was seen throughout the tumor prior to ablation. At gray-scale US, ablation produced hyperechoic foci, which were within 1 mm of the foci identified at histopathologic examination in seven of 12 animals (58%). After the administration of contrast material, foci devoid of previously visualized enhancement, which measured 7.3-15.0 mm, were identified. These were within 1 mm of the size of the foci identified at histopathologic examination in 11 of 12 animals (92%, P < .01). In two animals, enhancement depicted viable tumor, which appeared hyperechoic, on nonenhanced images. On delayed images, hyperechoic areas decreased in size, whereas the nonenhanced region remained unchanged. CONCLUSION: A PLGA microspherical US contrast agent enabled the immediate detection of coagulation necrosis as a region devoid of contrast enhancement after radio-frequency ablation in rabbit hepatic tumors. Therefore, this agent could provide real-time guidance during complex ablative procedures and may provide an efficient technique for postprocedural assessment.