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.

Real-Time Transcranial Histotripsy Treatment Localization and Mapping Using Acoustic Cavitation Emission Feedback.

Cavitation events generated during histotripsy therapy generate large acoustic cavitation emission (ACE) signals that can be detected through the skull. This article investigates the feasibility of using these ACE signals, acquired using the elements of a 500-kHz, 256-element hemispherical histotripsy transducer as receivers, to localize and map the cavitation activity in real time through the human skullcap during transcranial histotripsy therapy. The locations of the generated cavitation events predicted using the ACE feedback signals in this study were found to be accurate to within <1.5 mm of the centers of masses detected by optical imaging and found to lie to within the measured volumes of the generated cavitation events in >~80 % of cases. Localization results were observed to be biased in the prefocal direction of the histotripsy array and toward its transverse origin but were only weakly affected by focal steering location. The choice of skullcap and treatment pulse repetition frequency (PRF) were both observed to affect the accuracy of the localization results in the low PRF regime (1-10 Hz), but the localization accuracy was seen to stabilize at higher PRFs (≥10 Hz). Tests of the localization algorithm in vitro, for treatment delivered to a bovine brain sample mounted within the skullcap, revealed good agreement between the ACE feedback-generated treatment map and the morphological characteristics of the treated volume of the brain sample. Localization during experiments was achieved in real time for pulses delivered at rates up to 70 Hz, but benchmark tests indicate that the localization algorithm is scalable, indicating that higher rates are possible with more powerful hardware. The results of this article demonstrate the feasibility of using ACE feedback signals to localize and map transcranially generated cavitation events during histotripsy. Such capability has the potential to greatly simplify transcranial histotripsy treatments, as it may provide a non-MRI-based method for monitoring and localizing transcranial histotripsy treatments in real time.

Comparative study of the dynamics of laser and acoustically generated bubbles in viscoelastic media.

Experimental observations of the growth and collapse of acoustically and laser-nucleated single bubbles in water and agarose gels of varying stiffness are presented. The maximum radii of generated bubbles decreased as the stiffness of the media increased for both nucleation modalities, but the maximum radii of laser-nucleated bubbles decreased more rapidly than acoustically nucleated bubbles as the gel stiffness increased. For water and low stiffness gels, the collapse times were well predicted by a Rayleigh cavity, but bubbles collapsed faster than predicted in the higher stiffness gels. The growth and collapse phases occurred symmetrically (in time) about the maximum radius in water but not in gels, where the duration of the growth phase decreased more than the collapse phase as gel stiffness increased. Numerical simulations of the bubble dynamics in viscoelastic media showed varying degrees of success in accurately predicting the observations.

Non-invasive, Rapid Ablation of Tissue Volume Using Histotripsy.

Histotripsy is a non-invasive, non-thermal ablation technique that uses high-amplitude, focused ultrasound pulses to fractionate tissue via acoustic cavitation. The goal of this study was to illustrate the potential of histotripsy with electronic focal steering to achieve rapid ablation of a tissue volume at a rate matching or exceeding those of current clinical techniques (∼1-2 mL/min). Treatment parameters were established in tissue-mimicking phantoms and applied to ex vivo tissue. Six-microsecond pulses were delivered by a 250-kHz array. The focus was electrically steered to 1000 locations at a pulse repetition frequency of 200 Hz (0.12% duty cycle). Magnetic resonance imaging and histology of the treated tissue revealed a distinct region of necrosis in all samples. Mean lesion volume was 35.6 ± 4.3 mL, generated at 0.9-3.3 mL/min, a speed faster than that of any current ablation method for a large volume. These results suggest that histotripsy has the potential to achieve non-invasive, rapid, homogeneous ablation of a tissue volume.