Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose.
Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose.
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乙基纤维增强乙醇定位和消融程度的放射病理学分析。
DOI：
10.1038/s41598-021-99985-4
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发表时间：
2021-10-19
影响因子：
4.6
通讯作者：
Ramanujam N
中科院分区：
文献类型：
--
作者：
Chelales E;Morhard R;Nief C;Crouch B;Everitt JI;Sag AA;Ramanujam N
乙醇为肝肿瘤提供了一种快速、低成本的消融解决方案，技术占地面积小，但存在靶组织扩散不受控制的问题，限制了治疗的精确度和准确性。在乙醇中加入凝胶形成聚合物乙基纤维素可以定位分布。本研究的目的是建立一种基于CT成像的非侵入性方法学，以定量确定EC-乙醇制剂的给药参数、其分布和相应的坏死体积之间的关系。用水-乙醇替代物表征了放射性密度与乙醇浓度的关系。体外EC-乙醇消融以优化处方(n = 6)。体内消融比较最佳的EC-乙醇配方和纯乙醇(n = 6)。用CT监测消融情况，并量化酒精分布体积。取肝脏，切片，NADH-黄递酶染色以确定消融程度，并进行详细的时间-过程组织学研究以评估创面愈合过程。乙醇-水替代物的CT成像显示乙醇浓度-放射性密度关系近似线性。在体外，浓度为12%的EC在乙醇中产生了最大的分布体积，是纯乙醇的8倍多。在体内，12%EC-乙醇优于纯乙醇，产生的分布体积是纯乙醇的3倍，消融区域是纯乙醇的6倍。最后，12%EC-乙醇和纯乙醇消融后肝脏的时间进程组织学评估显示，虽然在消融后1-4周，两者都引起凝固性坏死和相似的组织反应，但12%EC-乙醇产生了更大的消融区域。目前的研究证明了CT成像在确定组织中乙醇的分布、体积和浓度方面的适用性。与纯乙醇相比，EC-乙醇的分布体积几乎相当于所产生的坏死体积，并且增加了分布和坏死。
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.
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