Experimental and Computational Analysis of High-Intensity Focused Ultrasound Thermal Ablation in Breast Cancer Cells: Monolayers vs. Spheroids

Simple Summary Breast cancer is a significant global health challenge, ranking as the second leading cause of death worldwide. Current treatment modalities, such as invasive surgery and chemotherapy, while effective to some extent, pose notable risks to patient well-being. High-intensity focused ultrasound (HIFU) offers a non-invasive alternative, utilizing precise acoustic energy for targeted tumor ablation while sparing surrounding healthy tissues. However, HIFU's efficacy depends on various factors, necessitating comprehensive research for optimization. The research focuses on in vitro thermal ablation of epithelial breast cancer cell lines, exploring the impact of HIFU on both 2D monolayer and 3D spheroidal cell configurations. The investigation assesses ultrasound parameters, including acoustic intensity, duty cycle, and sonication duration, evaluating their influence on temperature elevation and tumor cell ablation. Empirical findings are compared with numerical simulations, contributing to a deeper understanding of HIFU's potential in breast cancer treatment and paving the way for more effective therapeutic strategies.Abstract High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic modality that uses precise acoustic energy to ablate cancerous tissues through coagulative necrosis. In this context, we investigate the efficacy of HIFU ablation in two distinct cellular configurations, namely 2D monolayers and 3D spheroids of epithelial breast cancer cell lines (MDA-MB 231 and MCF7). The primary objective is to compare the response of these two in vitro models to HIFU while measuring their ablation percentages and temperature elevation levels. HIFU was systematically applied to the cell cultures, varying ultrasound intensity and duty cycle during different sonication sessions. The results indicate that the degree of ablation is highly influenced by the duty cycle, with higher duty cycles resulting in greater ablation percentages, while sonication duration has a minimal impact. Numerical simulations validate experimental observations, highlighting a significant disparity in the response of 2D monolayers and 3D spheroids to HIFU treatment. Specifically, tumor spheroids require lower temperature elevations for effective ablation, and their ablation percentage significantly increases with elevated duty cycles. This study contributes to a comprehensive understanding of acoustic energy conversion within the biological system during HIFU treatment for 2D versus 3D ablation targets, holding potential implications for refining and personalizing breast cancer therapeutic strategies.