Non-thermal ultrasound-guided fractionation of human leiomyosarcoma with boiling histotripsy: an ex vivo feasibility study.

OBJECTIVE

Leiomyosarcoma (LMS) is a malignant very aggressive tumor, composed of cells exhibiting smooth muscle differentiation, and one of the most common types of soft tissue sarcomas. Here the feasibility of a non-invasive ultrasound-based approach for mechanical fractionation of human LMS, termed boiling histotripsy (BH), was evaluated ex vivo.

METHODS

Three autopsy samples of human retroperitoneal LMS were subjected to stiffness measurements via shear wave elastography, followed by a volumetric BH treatment using a custom-made focused ultrasound transducer (1.5 MHz, 12 sectors, F# = 0.75) under diagnostic ultrasound guidance. Volumetric BH lesions (170-230 mm3) were produced in LMS samples through sonication over a 3D grid of foci (2-3 layers of 5 × 5 foci with 1-mm step) with 1 ms or 2 ms pulses delivered 150 or 80 times per focus with 1 % duty cycle (P+/P-/As = 167/-26/179 MPa insitu). BH sonications were performed within 14-20 min and corresponding BH-induced tissue damage was evaluated histologically with H&E staining.

RESULTS

Stiffness of autopsy LMS tissue was within the broad range observed clinically. BH treatments were successfully planned and guided with diagnostic ultrasound. Complete liquefaction and cellular disruption of the target tumor volume with sharp boundaries between intact and fractionated tissue was confirmed histologically.

CONCLUSION

This pilot study demonstrates the feasibility of boiling histotripsy for non-invasive ultrasound-guided mechanical fractionation of human LMS ex vivo, initiating further extended optimization studies.