Synergetic Ablation of Tumors with Focused Ultrasound and Ethanol

date January 24, 2014
comments no comments.

Friday, January 24, 2014 4:00 p.m. ETC 4.150

Dr. Damir B. Khismatullin
Department of Biomedical Engineering
Tulane University
https://tulane.edu/sse/bme

Focused ultrasound (FUS) emerges as a powerful technology for noninvasive, or minimally invasive, non-ionizing treatment of cancer and many other diseases. When operated at high intensity, FUS deposits a large amount of acoustic energy at the focal region within the target tissue (e.g., tumor), causing tissue heating and necrosis, the process known as thermal ablation. When operated at low intensity, FUS is capable of increasing the proliferative potential and functionality of living cells such as neurons and bone cells. As such, it can be used as a tool to treat neurodegenerative diseases, nerve injuries, and bone fractures. The major focus of previous studies was on using FUS as a standalone therapeutic method. Several deficiencies of standalone FUS (e.g., small area of treated tissue, lengthy procedure, sophisticating scanning protocol) prevented its widespread use in clinics and approval by the FDA. In this talk, I will present recent in vitro and in vivo data from my laboratory showing that FUS is much more effective in therapy when it is used as an adjuvant to other therapeutic methods. According to our experiments, high-intensity focused ultrasound (HIFU) applied to tumors already exposed to ethanol lead to almost complete destruction of tumor cells even when the ethanol dose is much less than used in percutaneous ethanol injection (PEI), one of FDA-approved methods of chemical ablation. We hypothesize that this synergistic effect of HIFU and ethanol is caused by 1) enhanced delivery of chemical agents into tumor cells via HIFU‑induced acoustic streaming in tumor tissue and reducing the cell membrane permeability by the sonoporation phenomenon, and 2) enhanced tissue heating rate by HIFU due to ethanol-induced localized reduction of the cavitation threshold. Key results are that 1) the HIFU ablation lesion volume increases dramatically and becomes more spherical (note that HIFU focal region is ellipsoidal in shape) with pre-treatment of tissues with ethanol, and 2) ethanol + HIFU but not ethanol alone or HIFU alone can completely eliminate cancer in xenograft mouse models.  In the end of the talk, I will discuss our new project on spinal cord injury treatment by FUS and molecular medicine.