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(Radiology. 1999;213:438-444.)
© RSNA, 1999


Experimental Studies

Radio-frequency-induced Coagulation Necrosis in Rabbits: Immediate Detection at US with a Synthetic Microsphere Contrast Agent1

S. Nahum Goldberg, MD, Richard C. Walovitch, PhD, Julie A. Straub, PhD, Mary Theresa Shore, RTR and G. Scott Gazelle, MD, MPH

1 From the Department of Radiology, Massachusetts General Hospital, Boston, Mass (S.N.G., M.T.S., G.S.G.) and the Department of Research and Development, Acusphere, Cambridge, Mass (R.C.W., J.A.S.). Received August 25, 1998; revision requested October 28; final revision received February 18, 1999; accepted April 6. Supported in part by grants from Radionics, Burlington, Mass. S.N.G. supported in part by the RSNA Research and Education Foundation as a 1997 Cesare Gianturco/RSNA Fellow supported by the Cook Group. Address reprint requests to S.N.G., Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215 (e-mail: sgoldber@caregroup .harvard.edu).   G.S.G. is a paid consultant to Acusphere. R.C.W. and J.A.S. are employees of Acusphere.

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-µm diameter) filled with perfluorocarbon gas. Radio frequency was applied to each nodule for 6 minutes at 127 mA ± 33 (mean ± SD) (tip temperature, 92°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.

Index terms: Animals • Liver neoplasms, US, 761.321, 761.12988 • Radiofrequency (RF) ablation, 761.1269 • Ultrasound (US), contrast media, 761.12988 • Ultrasound (US), Doppler studies, 761.12983, 761.12988




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