Advances in Miniature Ultrasound-guided Histotripsy Transducers for Precision Tissue Ablation

Abstract

Histotripsy is a type of focused ultrasound therapy that uses a very high focal pressure to ablate (surgically remove) tumors with high precision, without damaging the surrounding healthy tissue. Unlike other ablation modalities there is no risk of thermal injury or ionizing radiation exposure because it uses the mechanical forces produced by a cavitation bubble cloud to kill cells. Many surgeons are moving toward minimally invasive procedures due to significant benefits compared to open surgery, such as reduced blood loss, shorter hospital stays, less pain and faster recovery times. The goal of this work is to develop a high precision surgical device for minimally invasive neurosurgery that combines ultrasound imaging and histotripsy. The first study explored a dual frequency (1.2- and 5-MHz) histotripsy transducer with a 5 mm square aperture. The quarter wavelength coupling layer behind the 5 MHz transducer resulted in a pressure output similar to an air backing, while the output from the 1.2 MHz transducer added to the overall focal pressure. The dual frequency device was tested on an ex vivo rat brain, ablating tissue at up to 4 mm depth, with lesion sizes as small as 500 μm. The second study involved evaluating several piezoelectric materials for use in miniature histotripsy transducers. Five piezoelectric ceramics were evaluated, including PZT 5A, PZT-5H (CTS 3203HD), Pz39, Pz54 and PMN-38. 5 MHz, 1-3 dice and fill, piezo/epoxy composites were fabricated for all except Pz39, a low acoustic impedance porous ceramic. For each, four air-backed 8 mm diameter aluminum lens transducers were built and tested. PZT-5H was identified as the best material from this set. In the third study, an 8 mm diameter annular array histotripsy transducer was fabricated and tested, motivated by eliminating the lens curvature and providing axial focal steering capability. The histotripsy array was designed to be co-registered with a 30 MHz phased array imaging probe. Real time B-mode and Doppler imaging were used to target tissue and monitor ablation progress, while producing an elongated lesion in vivo in a rat brain by rapidly steering from 3- to 8-mm. Histology confirmed the targeted tissue was fully homogenized.