Study of Biological Effects Induced in Solid Tumors by Shortened-Duration Thermal Ablation Using High-Intensity Focused Ultrasound

Author:

Kaplińska-Kłosiewicz Patrycja Maria1,Fura Łukasz2,Kujawska Tamara2ORCID,Andrzejewski Kryspin3ORCID,Kaczyńska Katarzyna3ORCID,Strzemecki Damian1,Sulejczak Mikołaj4,Chrapusta Stanisław J.1ORCID,Macias Matylda5,Sulejczak Dorota1ORCID

Affiliation:

1. Department of Experimental Pharmacology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5 St., 02-106 Warsaw, Poland

2. Department of Ultrasound, Institute of Fundamental Technological Research, Polish Academy of Sciences, Pawinskiego 5b St., 02-106 Warsaw, Poland

3. Department of Respiration Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5 St., 02-106 Warsaw, Poland

4. Department of Animal Physiology, Faculty of Biology, University of Warsaw, I. Miecznikowa 1 St., 02-096 Warsaw, Poland

5. Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena 4 St., 02-109 Warsaw, Poland

Abstract

The HIFU ablation technique is limited by the long duration of the procedure, which results from the large difference between the size of the HIFU beam’s focus and the tumor size. Ablation of large tumors requires treating them with a sequence of single HIFU beams, with a specific time interval in-between. The aim of this study was to evaluate the biological effects induced in a malignant solid tumor of the rat mammary gland, implanted in adult Wistar rats, during HIFU treatment according to a new ablation plan which allowed researchers to significantly shorten the duration of the procedure. We used a custom, automated, ultrasound imaging-guided HIFU ablation device. Tumors with a 1 mm thickness margin of healthy tissue were subjected to HIFU. Three days later, the animals were sacrificed, and the HIFU-treated tissues were harvested. The biological effects were studied, employing morphological, histological, immunohistochemical, and ultrastructural techniques. Massive cell death, hemorrhages, tissue loss, influx of immune cells, and induction of pro-inflammatory cytokines were observed in the HIFU-treated tumors. No damage to healthy tissues was observed in the area surrounding the safety margin. These results confirmed the efficacy of the proposed shortened duration of the HIFU ablation procedure and its potential for the treatment of solid tumors.

Funder

National Science Centre

ESF

Publisher

MDPI AG

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