title: Synergistic ablation of liver tissue and liver cancer cells with high-intensity focused ultrasound and ethanol.
abstract: We investigated the combined effect of ethanol and high-intensity focused ultrasound (HIFU), first, on heating and cavitation bubble activity in tissue-mimicking phantoms and porcine liver tissues and, second, on the viability of HepG2 liver cancer cells. Phantoms or porcine tissues were injected with ethanol and then subjected to HIFU at acoustic power ranging from 1.2 to 20.5 W (HIFU levels 1-7). Cavitation events and the temperature around the focal zone were measured with a passive cavitation detector and embedded type K thermocouples, respectively. HepG2 cells were subjected to 4% ethanol solution in growth medium (v/v) just before the cells were exposed to HIFU at 2.7, 8.7 or 12.0 W for 30 s. Cell viability was measured 2, 24 and 72 h post-treatment. The results indicate that ethanol and HIFU have a synergistic effect on liver cancer ablation as manifested by greater temperature rise and lesion volume in liver tissues and reduced viability of liver cancer cells. This effect is likely caused by reduction of the cavitation threshold in the presence of ethanol and the increased rate of ethanol diffusion through the cell membrane caused by HIFU-induced streaming, sonoporation and heating.
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Nguyen H
authors.initials: NH
authors.lastname: Hoang
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Hakm Y
authors.initials: HY
authors.lastname: Murad
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Sithira H
authors.initials: SH
authors.lastname: Ratnayaka
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA. Electronic address: Damir@tulane.edu.
authors.forename: Damir B
authors.initials: DB
authors.lastname: Khismatullin
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy / Q000379:methods; D000431:Ethanol / Q000627:therapeutic use*; D056945:Hep G2 Cells; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006358:Hot Temperature; D006801:Humans; D008099:Liver; D008113:Liver Neoplasms / Q000601:surgery*; D019047:Phantoms, Imaging; D012997:Solvents / Q000627:therapeutic use; D013552:Swine; D016896:Treatment Outcome
chemical_list: D012997:Solvents; D000431:Ethanol
keywords: Ablation; Acoustic Streaming; Cavitation; Ethanol; High-intensity focused ultrasound; Liver cancer; Sonoporation