Fabrication and characterization of a flat aperture Fresnel lens based histotripsy transducer.

Two single element, 8 mm focal depth, 6 MHz PZT-5A 40% volume fraction 1-3 composite Fresnel aluminum lens based therapeutic ultrasound transducers for use in small animal histotripsy applications were built with 15 mm outer diameters - one with a central hole of 5.7 mm diameter for future co-registration and one full-aperture. The device was built with the front face filled with acoustically transparent epoxy to create a flat aperture allowing gel-coupling to tissue, where the Fresnel lens design allowed flattening of the aperture with minimal epoxy fill. Epoxy fill resulted in a 6% loss of focal pressure. The full-aperture device achieved 37 MPa/100 V peak-to-peak focal pressures with the removed center element device achieving 25 MPa/100V - a 32% reduction, which matches COMSOL simulated results. Pulsing between 190 V and 270 V at 17 cycles and 1 kHz PRF, the full-aperture device generated bubble clouds in water ranging from 0.31 mm to 0.51 mm radially, and 0.53 mm to 0.81 mm axially. Cavitation for the removed center element device was observed to begin at 370 V, and was consistent at 400 V.

Fabrication and Characterization of a 5 mm × 5 mm Aluminum Lens-Based Histotripsy Transducer.

Two 5 mm by 5 mm square aluminum lenses with a 6 mm depth of focus were machined and tested for histotripsy with a 40% volume fraction 1-3 PZT-5A composite and a Meggitt Pz-39 porous ceramics lapped to 315 [Formula: see text] as the piezoelectric elements. The devices were air-backed, and an 89 [Formula: see text] layer of Parylene-C was deposited on the lens, matching aluminum to water. Both devices were driven single-ended at 5.8 MHz, their optimal frequency after bonding to the lens, with ten cycles at a PRF of 1 kHz. The composite-based device showed no sign of free-field cavitation in water up to a drive level of 600 V, whereas the Pz39-based device was able to cavitate in water at a drive level of 220 V. In vivo ablation of a rat brain tissue was demonstrated through an opening in the skull and required the drive voltage be increased to 280 V. The ablation was monitored using B-mode imaging with an endoscopic 30 MHz ultrasound phased array and power Doppler overlay. Ablation was maintained for 12 s and, in the power Doppler image, the ablation zone grew steadily over this time to 1.9 mm by 3.4 mm. Immediately after treatment, the ablated area appeared anechoic, slowly filling with specular material.

Endoscopic Coregistered Ultrasound Imaging and Precision Histotripsy: Initial In Vivo Evaluation.

Objective. Initial performance evaluation of a system for simultaneous high-resolution ultrasound imaging and focused mechanical submillimeter histotripsy ablation in rat brains. Impact Statement. This study used a novel combination of high-resolution imaging and histotripsy in an endoscopic form. This would provide neurosurgeons with unprecedented accuracy in targeting and executing nonthermal ablations in minimally invasive surgeries. Introduction. Histotripsy is a safe and effective nonthermal focused ablation technique. However, neurosurgical applications, such as brain tumor ablation, are difficult due to the presence of the skull. Current devices are too large to use in the minimally invasive approaches surgeons prefer. We have developed a combined imaging and histotripsy endoscope to provide neurosurgeons with a new tool for this application. Methods. The histotripsy component had a 10 mm diameter, operating at 6.3 MHz. Affixed within a cutout hole in its center was a 30 MHz ultrasound imaging array. This coregistered pair was used to ablate brain tissue of anesthetized rats while imaging. Histological sections were examined, and qualitative descriptions of ablations and basic shape descriptive statistics were generated. Results. Complete ablations with submillimeter area were produced in seconds, including with a moving device. Ablation progress could be monitored in real time using power Doppler imaging, and B-mode was effective for monitoring post-ablation bleeding. Collateral damage was minimal, with a 100 µm maximum distance of cellular damage from the ablation margin. Conclusion. The results demonstrate a promising hardware suite to enable precision ablations in endoscopic procedures or fundamental preclinical research in histotripsy, neuroscience, and cancer.

A Dual-Frequency Lens-Focused Endoscopic Histotripsy Transducer.

A forward-looking miniature histotripsy transducer has been developed that incorporates an acoustic lens and dual-frequency stacked transducers. An acoustic lens is used to increase the peak negative pressure through focal gain and the dual-frequency transducers are designed to increase peak negative pressure by summing the pressure generated by each transducer individually. Four lens designs, each with an f -number of approximately 1, were evaluated in a PZT5A composite transducer. The finite-element model (FEM) predicted axial beamwidths of 1.61, 2.40, 2.84, and 2.36 mm for the resin conventional, resin Fresnel, silicone conventional, and silicone Fresnel lenses, respectively; the measured axial beamwidths were 1.30, 2.28, 2.71, and 2.11 mm, respectively. Radial beamwidths from the model were between 0.32 and 0.35 mm, while measurements agreed to within 0.2 mm. The measured peak negative was 0.150, 0.124, 0.160, and 0.160 MPa/V for the resin conventional, resin Fresnel, silicone conventional, and silicone Fresnel lenses, respectively. For the dual-frequency device, the 5-MHz (therapy) transducer had a measured peak negative pressure of 0.136 MPa/V for the PZT5A composite and 0.163 MPa/V for the PMN-PT composite. The 1.2-MHz (pump) transducer had a measured peak negative pressure of 0.028 MPa/V. The pump transducer significantly lowered the cavitation threshold of the therapy transducer. 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 [Formula: see text].

A Low-Cost Miniature Histotripsy Transducer for Precision Tissue Ablation.

A miniature, 10 mm aperture histotripsy transducer with an f-number of 0.7 was fabricated using an elliptically shaped aluminum lens, which was epoxy-bonded to an air-backed 5.0 MHz, PTZ-5A, 1-3 dice-and-fill piezoelectric composite, and the lens coupled to water using a quarter-wavelength matching layer of Parylene-C. A Krimholtz-Leedom-Matthaei model of the device and curved lens was developed. The epoxy layer resulted in an increased power output at 6.8 MHz compared to the 5 MHz composite design. Cavitation was observed in water by driving the composite with a 173 V single-cycle, unipolar 6.8 MHz pulse at a pulse repetition frequency of 50 Hz, and a bubble cloud 264 long by 124 wide was measured. A coregistered imaging and ablation device was also fabricated and characterized. The coregistered device was modified to include a mm square hole through the center, allowing access for a high-frequency imaging array, and both imaging and ablation are demonstrated in cerebral tissue with this device. Radial -3 dB beam widths were measured as 0.145 and 0.116 mm, and axial -3 dB depths of field were 0.698 and 0.752 mm for the noncoregistered and coregistered transducers, respectively. Total material cost for the transducer and pulser board is below $200 USD.