Abstract
Ethanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. The purpose of this study was to establish a non-invasive methodology based on CT imaging to quantitatively determine the relationship between the delivery parameters of the EC-ethanol formulation, its distribution, and the corresponding necrotic volume. The relationship of radiodensity to ethanol concentration was characterized with water–ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n = 6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n = 6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were removed, sectioned and stained with NADH-diaphorase to determine the ablative extent, and a detailed time-course histological study was performed to assess the wound healing process. CT imaging of ethanol–water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than eight-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume three-fold greater and an ablation zone six-fold greater than pure ethanol. Finally, a time course histological evaluation of the liver post-ablation with 12% EC-ethanol and pure ethanol revealed that while both induce coagulative necrosis and similar tissue responses at 1–4 weeks post-ablation, 12% EC-ethanol yielded a larger ablation zone. The current study demonstrates the suitability of CT imaging to determine distribution volume and concentration of ethanol in tissue. The distribution volume of EC-ethanol is nearly equivalent to the resultant necrotic volume and increases distribution and necrosis compared to pure ethanol.
Highlights
Ethanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy
The current study demonstrates suitability of computed tomography (CT) imaging to define the delivery and uptake parameters of ECethanol in order to achieve near equivalence of the ethyl cellulose (EC)-ethanol distribution volume to the necrotic volume
The equivalency of these two volumes indicates that the distribution volume as determined by ethanol concentration extraction and concentration-based thresholding via CT imaging is an accurate representation of the resultant ablative effect
Summary
Low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Thermal ablation is established as a curative treatment for hepatocellular carcinoma (HCC) in the Barcelona Clinic Liver Cancer staging c riteria[7]. Compared to surgery it is less expensive[8], less invasive9, faster[10] and requires shorter hospital stays[11]. For ethanol ablation to be an effective alternative to thermal ablation, ethanol must be localized within the target tissue[18] To achieve this goal in the treatment of venous malformations and herniated discs, ethanol is mixed with the water-insoluble polymer ethyl cellulose (EC) prior to injection[19,20]. EC-ethanol ablation reduced tumor volume and was demonstrated as feasible in the treatment of felines with squamous cell carcinomas[23]
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