Yang Jeffrey, Ma Xihan, Mikhail Andrew S, Pritchard William F, Wood Bradford J, Zhang Haichong K, Mueller Jenna L
Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Sci Rep. 2025 Jul 15;15(1):25596. doi: 10.1038/s41598-025-11336-9.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths worldwide. While surgery and liver transplantation are curative treatments for HCC, many tumors are unresectable due to co-morbidities or advanced stage. Ethanol ablation is an established alternative ablative therapy for HCC that is typically paired with ultrasound imaging to visualize tumors and enable precise ethanol delivery. However, ethanol has the propensity to leak from the injection site and is not inherently echogenic, making biodistribution difficult to monitor. To address these limitations, we added ethyl cellulose (EC) with ethanol to form a gel that improves ethanol retention and generates an echogenic depot in tissue. We performed studies in tissue phantoms and liver tissue to characterize the acoustic profile of the EC-ethanol depots. Studies in phantoms showed that the EC-ethanol depots were 1.5x more echogenic when EC-ethanol ratios increased from 6 to 12% (p < 0.001). EC-ethanol depots in excised liver tissue and in swine liver post-mortem were acoustically discernable and generated 4 cm depots, which are of clinically relevant size for HCC treatment. In summary, this study established the echogenic properties of EC-ethanol for spatiotemporal analysis of injectate distribution, demonstrating its translational potential for tracking biodistribution during liver ablation.
肝细胞癌（HCC）是全球第三大常见癌症死亡原因。虽然手术和肝移植是治疗HCC的根治性方法，但由于合并症或晚期阶段，许多肿瘤无法切除。乙醇消融是一种既定的HCC替代消融疗法，通常与超声成像配合使用，以可视化肿瘤并实现乙醇的精确递送。然而，乙醇容易从注射部位泄漏，并且本身不具有回声性，使得生物分布难以监测。为了解决这些局限性，我们将乙基纤维素（EC）与乙醇混合形成一种凝胶，该凝胶可改善乙醇的滞留并在组织中产生回声性贮库。我们在组织模型和肝组织中进行了研究，以表征EC-乙醇贮库的声学特征。在模型中的研究表明，当EC-乙醇比例从6%增加到12%时，EC-乙醇贮库的回声性提高了1.5倍（p < 0.001）。切除的肝组织和猪肝脏死后的EC-乙醇贮库在声学上是可辨别的，并且产生了4厘米的贮库，这对于HCC治疗具有临床相关的大小。总之，本研究确立了EC-乙醇用于注射剂分布的时空分析的回声特性，证明了其在肝消融期间追踪生物分布的转化潜力。
