In Vivo Cavitation-based Aberration Correction of Histotripsy in Porcine Liver.

Histotripsy is a non-invasive ablation technique that focuses ultrasound pulses into the body to destroy tissues via cavitation. Heterogeneous acoustic paths through tissue introduce phase errors that distort and weaken the focus, requiring additional power output from the histotripsy transducer to perform therapy. This effect, termed phase aberration, limits the safety and efficacy of histotripsy ablation. It has been shown in vitro that the phase errors from aberration can be corrected by receiving the acoustic signals emitted by cavitation. For transabdominal histotripsy in vivo, however, cavitation-based aberration correction is complicated by acoustic signal clutter and respiratory motion. This study develops a method that enables robust, effective cavitation-based aberration correction in vivo and evaluates its efficacy in the swine liver. The method begins with a high-speed pulsing procedure to minimize the effects of respiratory motion. Then, an optimal phase correction is obtained in the presence of acoustic clutter by filtering with the singular value decomposition. This aberration correction method reduced the power required to generate cavitation in the liver by 26% on average (range: 0% to 52%) and required ~2 s for signal acquisition and processing per focus location. These results suggest that the cavitation-based method could enable fast and effective aberration correction for transabdominal histotripsy.

A Model of High-Speed Endovascular Sonothrombolysis with Vortex Ultrasound-Induced Shear Stress to Treat Cerebral Venous Sinus Thrombosis.

This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis (CVST). This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20% to 40% of the cases, and the incidence of CVST has increased since the outbreak of the coronavirus disease 2019 pandemic. Compared with conventional anticoagulant or thrombolytic drugs, sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves. However, previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes (e.g., recanalization within 30 min) in treating large, completely occluded veins or arteries. Here, we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wave-matter interaction-induced shear stress to enhance the lytic rate substantially. Our in vitro experiment showed that the lytic rate was increased by at least 64.3% compared with the nonvortex endovascular ultrasound treatment. A 3.1-g, 7.5-cm-long, completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot in vitro. Furthermore, we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins. This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.

Monitoring cavitation dynamics evolution in tissue mimicking hydrogels for repeated exposures via acoustic cavitation emissions.

A 700 kHz histotripsy array is used to generate repeated cavitation events in agarose, gelatin, and polyacrylamide hydrogels. High-speed optical imaging, a broadband hydrophone, and the narrow-band receive elements of the histotripsy array are used to capture bubble dynamics and acoustic cavitation emissions. Bubble radii, lifespan, shockwave amplitudes are noted to be measured in close agreement between the different observation methods. These features also decrease with increasing hydrogel stiffness for all of the tested materials. However, the evolutions of these properties during the repeated irradiations vary significantly across the different material subjects. Bubble maximum radius initially increases, then plateaus, and finally decreases in agarose, but remains constant across exposures in gelatin and polyacrylamide. The bubble lifespan increases monotonically in agarose and gelatin but decreases in polyacrylamide. Collapse shockwave amplitudes were measured to have different-shaped evolutions between all three of the tested materials. Bubble maximum radii, lifespans, and collapse shockwave amplitudes were observed to express evolutions that are dependent on the structure and stiffness of the nucleation medium.

A Modular, Kerf-Minimizing Approach for Therapeutic Ultrasound Phased Array Construction.

A novel method for fabricating a modular, kerf-minimizing histotripsy phased array was developed and tested. The method utilizes arbitrarily shaped elements, 3-D printing, water jet cutting, and a thin, 125- [Formula: see text] electrically insulating epoxy coating to maximize aperture utilization while allowing for replacement of individual transducer modules. The method was used to fabricate a 750-kHz truncated circular aperture array (165 mm ×234 mm) transducer with a focal length of 142 mm. The aperture was segmented into 260 arc-shaped modular elements, each approximately 11.5 mm ×11.5 mm, arranged in concentric rings. The resulting aperture utilization was 92%. The full-width-half-maximum (FWHM) focal zone of the array was measured to be 1.6 mm ×1.1 mm ×4.5 mm, and the FWHM electrical steering range was measured to be 38.5 mm ×33 mm 40 mm. The array was estimated to be capable of generating approximately 120-MPa peak negative pressure at the geometric focus. In addition, the array was used to ablate a 5-cm3 volume of tissue with electric focal steering.

In Vivo Porcine Aged Deep Vein Thrombosis Model for Testing Ultrasound-based Thrombolysis Techniques.

As blood clots age, many thrombolytic techniques become less effective. To fully evaluate these techniques for potential clinical use, a large animal aged-clot model is needed. Previous minimally invasive attempts to allow clots to age in an in vivo large animal model were unsuccessful because of the clot clearance associated with relatively high level of cardiac health of readily available research pigs. Prior models have thus subsequently used invasive surgical techniques with the associated morbidity, animal stress and cost. We propose a method for forming sub-acute venous blood clots in an in-vivo porcine model. The age of the clots can be controlled and varied. By using an intravenous scaffold to anchor the clot to the vessel wall during the aging process, we can show that sub-acute clots can consistently be formed with a minimally invasive, percutaneous approach. The clot formed in this study remained intact for at least 1 wk in all subjects. Therefore, we established a new minimally invasive, large animal aged-clot model for evaluation of thrombolytic techniques.

Endocavity Histotripsy for Efficient Tissue Ablation-Transducer Design and Characterization.

A 34-mm aperture transducer was designed and tested for proof of concept to ablate tissues using an endocavity histotripsy device. Several materials and two drivers were modeled and tested to determine an effective piezoelectric-matching layer combination and driver design. The resulting transducer was fabricated using 1.5 MHz porous PZT and PerFORM 3-D printed acoustic lenses and was driven with a multicycle class-D amplifier. The lower frequency, compared to previously developed small form factor histotripsy transducers, was selected to allow for more efficient volume ablation of tissue. The transducer was characterized and tested by measuring pressure field maps in the axial and lateral planes and pressure output as a function of driving voltage. The axial and lateral full-width-half-maximums of the focus were found to be 6.1 and 1.1 mm, respectively. The transducer was estimated to generate 34.5-MPa peak negative focal pressure with a peak-to-peak driving voltage of 1345 V. Performance testing was done by ablating volumes of bovine liver tissues ( n = 3 ). The transducer was found to be capable of ablating tissues at its full working distance of 17 mm.