Jonathan R. Sukovich

Targeted Lesion Generation Through the Skull Without Aberration Correction Using Histotripsy

This study demonstrates the ability of histotripsy to generate targeted lesions through the skullcap without using aberration correction. Histotripsy therapy was delivered using a 500-kHz 256-element hemispherical transducer with an aperture diameter of 30 cm, and a focal distance of 15 cm fabricated in our laboratory. This transducer is theoretically capable of producing peak rarefactional pressures, based on linear estimation, (p-)LE, in the free field in excess of 200 MPa with pulse durations ≤2 acoustic cycles. Three excised human skullcaps were used displaying attenuations of 73%-81% of the acoustic pressure without aberration correction. Through all three skullcaps, compact lesions with radii less than 1 mm were generated in red blood cell agarose tissue phantoms without aberration correction, using estimated (p-)LE of 28-39 MPa, a pulse repetition frequency of 1 Hz, and a total number of 300 pulses. Lesion generation was consistently observed at the geometric focus of the transducer as the position of the skullcap with respect to the transducer was varied, and multiple-patterned lesions were generated transcranially by mechanically adjusting the position of the skullcap with respect to the transducer to target different regions within. These results show that compact targeted lesions with sharp boundaries can be generated through intact skullcaps using histotripsy with very short pulses without using aberration correction. Such capability has the potential to greatly simplify transcranial ultrasound therapy for noninvasive transcranial applications, as current ultrasound transcranial therapy techniques all require sophisticated aberration correction.

Effects of Temperature on the Histotripsy Intrinsic Threshold for Cavitation

Histotripsy is an ultrasound ablation method that depends on the initiation of a dense cavitation bubble cloud to fractionate soft tissue. Previous work has demonstrated that a cavitation cloud can be formed by a single acoustic pulse with one high-amplitude negative cycle, when the negative pressure amplitude exceeds a threshold intrinsic to the medium. The intrinsic thresholds in soft tissues and tissue phantoms that are water based are similar to the intrinsic threshold of water over an experimentally verified frequency range of 0.3-3 MHz. Previous work studying the histotripsy intrinsic threshold has been limited to experiments performed at room temperature (~20 °C). In this study, we investigate the effects of temperature on the histotripsy intrinsic threshold in water, which is essential to accurately predict the intrinsic thresholds expected over the full range of in vivo therapeutic temperatures. Based on previous work studying the histotripsy intrinsic threshold and classical nucleation theory, we hypothesize that the intrinsic threshold will decrease with increasing temperature. To test this hypothesis, the intrinsic threshold in water was investigated both experimentally and theoretically. The probability of generating cavitation bubbles was measured by applying a single pulse with one high-amplitude negative cycle at 1 MHz to distilled degassed water at temperatures ranging from 10 °C to 90 °C. Cavitation was detected and characterized by passive cavitation detection and high-speed photography, from which the probability of cavitation was measured versus pressure amplitude. The results indicate that the intrinsic threshold (the negative pressure at which the cavitation probability = 0.5) significantly decreases with increasing temperature, showing a nearly linear decreasing trend from 29.8 ±0.4 MPa at 10 °C to 14.9 ± 1.4 MPa at 90 °C. Overall, the results of this study support our hypothesis that the intrinsic threshold is highly dependent on the temperature of the medium, which may allow for better predictions of cavitation generation at body temperature in vivo and at the elevated temperatures commonly seen in high-intensity focused ultrasound regimes.

Shock‐controlled bubble cloud dynamics and light emission.

Cavitation bubble collapse can generate intense concentrations of mechanical energy, sufficient to erode even the hardest metals and to generate light emissions visible to the naked eye. In this talk we describe cavitation bubble cloud experiments carried out in spherical resonators at ambient and acoustic pressures up to 30 MPa. Key to our system is the ability to nucleate with temporal and spatial controls, which we achieve using dielectric breakdown in water from pulsed focused laser beams. Our observations show that the cloud dynamics are controlled by the repetitive emission of shock waves, which propagate outward from the inertial cloud collapse, reflect off of the sphere wall, and then converge on the resonator center. Shock convergence phenomena and light emission from compact cloud collapse will be discussed. [Work supported by the Impulse Devices, Inc.]

Real-time acoustic-based feedback for histotripsy therapy

Histotripsy uses high-pressure microsecond ultrasound pulses to generate cavitation to fractionate cells in target tissues. Two acoustic-based feedback mechanisms are being investigated to monitor histotripsy therapy in real-time. First, bubble-induced color Doppler (BICD) is received by an ultrasound probe co-aligned with the histotripsy transducer to monitor the cavitation-induced motion of residual cavitation nuclei in tissue throughout treatment. Second, acoustic backscatter of the histotripsy pulse from the cavitation bubbles is received by directly probing elements of histotripsy transducer to monitor acoustic emissions from the cavitation bubbles during treatment. In these experiments, histotripsy was applied to agarose phantoms and ex vivo tissue by a 112-element, 500 kHz semi-hemispherical ultrasound array with a 15 cm focal distance. The BICD signals were collected on a Verasonics system by an L7-4 probe. The BICD and backscatter signals were compared to high-speed optical images of cavitation i...

Laser nucleation of single bubbles and clouds in an acoustic resonator via pressure-dependent dielectric breakdown

Obtaining bubbles on demand at precise times and locations in a non-contact fashion can be useful in a variety of applications. Of special importance is the combination of laser nucleation with acoustics, so that bubbles are only just nucleated by the optics but grown to macroscopic size solely by the acoustics. We present theory and experiment for the non-thermal laser nucleation of bubbles in an acoustic field in the absence of significant absorbing/scattering particles. First we present theory and experiment for the threshold for dielectric breakdown in water, resolving the distinct minimum at 20 bar. Then, we present a method and results for nucleating single and multiple bubbles with temporal uncertainty of 5 ns, and spatial uncertainty of 1 mm. Results for bubble number and first cycle expansion are reported as functions of the timing of the nucleating laser pulse with respect to the acoustic field. [Work supported by Impulse Devices, Inc.]

Acoustic cavitation emission feedback to monitor tissue fractionation during histotripsy therapy

Histotripsy uses high-pressure, microsecond-long ultrasound pulses to generate a cloud of cavitation to fractionate cells in target tissues such as tumors, blood clots and brain applications. B-mode ultrasound has been used to detect the cavitation and tissue fractionation generated by histotripsy, but it requires a separate imaging probe and can only detect substantial amounts of tissue fractionation. In this study, a specialized circuit and digitizer was designed to allow all the elements of a 112-element array to transmit extremely high-pressure (>40MPa) histotripsy pulses and receive the low-pressure Acoustic Cavitation Emission (ACE) signals. ACE feedback can be achieved via the histotripsy array itself and may have a high sensitivity to detect tissue fractionation.

Rapid liquefaction of blood clots using histotripsy in an in vivo porcine intracerebral hemorrhage (ICH) model

Histotripsy is a noninvasive ultrasound therapy that fractionates target tissues via cavitation. Our group has previously demonstrated that histotripsy can be delivered transcranially through excised human skulls to rapidly liquefy large volume clots for catheter aspiration using electronic focal steering (up to 40mL in 20 min) in an ex vivo ICH model. Transcranial MRgFUS has been investigated for ICH treatment, but is much slower (40mL in 3 hours), and limited to deep targets due to prefocal skull heating. The objective of this study was to demonstrate the feasibility of using histotripsy to liquefy clots for catheter aspiration in an in vivo porcine ICH model.

Investigation of the source of histotripsy acoustic backscatter signals

Recent work has demonstrated that acoustic backscatter signals from histotripsy-generated bubble clouds may be used to localize generated bubble clouds and perform non-invasive aberration correction transcranially. However, the primary source of the measured signals, whether from emissions generated during bubble expansion, or scattering of the incoming pulses off of the incipient bubble clouds, remains to be determined and may have important implications for how the acquired signals may be used. Here, we present results from experiments comparing the acoustic emissions and growth-collapse curves of single bubbles generated optically to those generated via histotripsy. Histotripsy bubbles were generated using a 32-element, 1.5 MHz spherical transducer with pulse durations <2-cycles; optical bubbles were nucleated using a pulsed Nd:YAG laser focused at the center of the histotripsy transducer. Optical imaging was used to capture the time evolution of the generated bubbles from inception to collapse. Acoust...

Transcranial histotripsy acoustic-backscatter localization and aberration correction for volume treatments

Here, we present results from experiments using histotripsy pulses backscattered off of therapy-generated bubble clouds to perform point-by-point aberration correction and bubble cloud localization transcranially over large steering ranges to demonstrate the efficacy of these methods at improving treatment efficiency and mapping volumetric treatments. Histotripsy pulses were delivered through an ex vivo human skullcap mounted centrally within a 500 kHz, 256-element histotripsy transducer with transmit-receive capable elements. Electronic focal steering was used to steer the therapy focus through individual points spanning a 30 mm diameter volume centered about the transducers geometric focus. Backscatter signals from the generated bubble clouds were collected using array elements as receivers. Separate algorithms, based on time-domain information extracted from the collected signals, were used to perform aberration correction and localize the generated bubble clouds, respectively. The effectiveness of th...

Implementation of follicle monitoring system based on 3D ultrasound images

The monitoring and analysis of cattle follicle dynamics plays an important role in improving the cattle pregnancy rate, both theoretically and practically. In this paper, we demonstrate a follicle monitoring system based on 3D ultrasound image. This system integrates an image de-noising algorithm, edge detection algorithm and 3D reconstruction algorithm together using the MFC framework and OpenGL technologies. Using this system, we realize the following functions: image de-noising, follicle detection, follicle surface extraction, follicle 3D reconstruction, follicle volume calculation, etc.