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.

Neuronavigation-Guided Transcranial Histotripsy (NaviTH) System.

OBJECTIVE: The goal of the work described here was to develop the first neuronavigation-guided transcranial histotripsy (NaviTH) system and associated workflow for transcranial ablation. METHODS: The NaviTH system consists of a 360-element, 700 kHz transmitter-receiver-capable transcranial histotripsy array, a clinical neuronavigation system and associated equipment for patient-to-array co-registration and therapy planning and targeting software systems. A workflow for NaviTH treatments, including pre-treatment aberration correction, was developed. Targeting errors stemming from target registration errors (TREs) during the patient-to-array co-registration process, as well as focal shifts caused by skull-induced aberrations, were investigated and characterized. The NaviTH system was used in treatments of two <96 h post-mortem human cadavers and in experiments in two excised human skullcaps. RESULTS: The NaviTH was successfully used to create ablations in the cadaver brains as confirmed in post-treatment magnetic resonance imaging A total of three ablations were created in the cadaver brains, and targeting errors of 9, 3.4 and 4.4 mm were observed in corpus callosum, septum and thalamus targets, respectively. Errors were found to be caused primarily by TREs resulting from transducer tracking instrument design flaws and imperfections in the treatment workflow. Transducer tracking instrument design and workflow improvements reduced TREs to <2 mm, and skull-induced focal shifts, following pre-treatment aberration correction, were 0.3 mm. Total targeting errors of the NaviTH system following the noted improvements were 2.5 mm. CONCLUSIONS: The feasibility of using the first NaviTH system in a human cadaver model has been determined. Although accuracy still needs to be improved, the proposed system has the potential to allow for transcranial histotripsy therapies without requiring active magnetic resonance treatment guidance.

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.

Soft Tissue Aberration Correction for Histotripsy Using Acoustic Emissions From Cavitation Cloud Nucleation and Collapse.

OBJECTIVE: Phase aberration from soft tissue limits the efficacy of histotripsy, a therapeutic ultrasound technique based on acoustic cavitation. Previous work has shown that the acoustic emissions from cavitation can serve as "point sources" for aberration correction (AC). This study compared the efficacy of soft tissue AC for histotripsy using acoustic cavitation emissions (ACE) from bubble cloud nucleation and collapse. METHODS: A 750-kHz, receive-capable histotripsy array was pulsed to generate cavitation in ex vivo porcine liver through an intervening abdominal wall. Received ACE signals were used to determine the arrival time differences to the focus and compute corrective delays. Corrections from single pulses and from the median of multiple pulses were tested. DISCUSSION: On average, ACE AC obtained 96% ± 3% of the pressure amplitude obtained by hydrophone-based correction (compared with 71% ± 5% without AC). Both nucleation- and collapse-based corrections obtained >96% of the hydrophone-corrected pressure when using medians of ≥10 pulses. When using single-pulse corrections, nucleation obtained a range of 49%-99% of the hydrophone-corrected pressure, while collapse obtained 95%-99%. CONCLUSION: The results suggest that (i) ACE AC can recover nearly all pressure amplitude lost owing to soft tissue aberration and that (ii) the collapse signal permits robust AC using a small number of pulses.

Two-step aberration correction: application to transcranial histotripsy.

Objective: Phase aberration correction is essential in transcranial histotripsy to compensate for focal distortion caused by the heterogeneity of the intact skull bone. This paper improves the 2-step aberration correction (AC) method that has been previously presented and develops an AC workflow that fits in the clinical environment, in which the computed tomography (CT)-based analytical approach was first implemented, followed by a cavitation-based approach using the shockwaves from the acoustic cavitation emission (ACE).Approach:A 700 kHz, 360-element hemispherical transducer array capable of transmit-and-receive on all channels was used to transcranially generate histotripsy-induced cavitation and acquire ACE shockwaves. For CT-AC, two ray-tracing models were investigated: a forward ray-tracing model (transducer-to-focus) in the open-source software Kranion, and an in-house backward ray-tracing model (focus-to-transducer) accounting for refraction and the sound speed variation in skulls. Co-registration was achieved by aligning the skull CT data to the skull surface map reconstructed using the acoustic pulse-echo method. For ACE-AC, the ACE signals from the collapses of generated bubbles were aligned by cross-correlation to estimate the corresponding time delays.Main results:The performance of the 2-step method was tested with 3 excised human calvariums placed at 2 different locations in the transducer array. Results showed that the 2-step AC achieved 90 ± 7% peak focal pressure compared to the gold standard hydrophone correction. It also reduced the focal shift from 0.84 to 0.30 mm and the focal volume from 10.6 to 2.0 mm3on average compared to the no AC cases.Significance:The 2-step AC yielded better refocusing compared to either CT-AC or ACE-AC alone and can be implemented in real-time for transcranial histotripsy brain therapy.

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.

Transcranial Magnetic Resonance-Guided Histotripsy for Brain Surgery: Pre-clinical Investigation.

Histotripsy has been previously applied to target various cranial locations in vitro through an excised human skull. Recently, a transcranial magnetic resonance (MR)-guided histotripsy (tcMRgHt) system was developed, enabling pre-clinical investigations of tcMRgHt for brain surgery. To determine the feasibility of in vivo transcranial histotripsy, tcMRgHt treatment was delivered to eight pigs using a 700-kHz, 128-element, MR-compatible phased-array transducer inside a 3-T magnetic resonance imaging (MRI) scanner. After craniotomy to open an acoustic window to the brain, histotripsy was applied through an excised human calvarium to target the inside of the pig brain based on pre-treatment MRI and fiducial markers. MR images were acquired pre-treatment, immediately post-treatment and 2-4 h post-treatment to evaluate the acute treatment outcome. Successful histotripsy ablation was observed in all pigs. The MR-evident lesions were well confined within the targeted volume, without evidence of excessive brain edema or hemorrhage outside of the target zone. Histology revealed tissue homogenization in the ablation zones with a sharp demarcation between destroyed and unaffected tissue, which correlated well with the radiographic treatment zones on MRI. These results are the first to support the in vivo feasibility of tcMRgHt in the pig brain, enabling further investigation of the use of tcMRgHt for brain surgery.

Transcranial MR-Guided Histotripsy System.

Histotripsy has been previously shown to treat a wide range of locations through excised human skulls in vitro. In this article, a transcranial magnetic resonance (MR)-guided histotripsy (tcMRgHt) system was developed, characterized, and tested in the in vivo pig brain through an excised human skull. A 700-kHz, 128-element MR-compatible phased-array ultrasound transducer with a focal depth of 15 cm was designed and fabricated in-house. Support structures were also constructed to facilitate transcranial treatment. The tcMRgHt array was acoustically characterized with a peak negative pressure up to 137 MPa in free field, 72 MPa through an excised human skull with aberration correction, and 48.4 MPa without aberration correction. The electronic focal steering range through the skull was 33.5 mm laterally and 50 mm axially, where a peak negative pressure above the 26-MPa cavitation intrinsic threshold can be achieved. The MR compatibility of the tcMRgHt system was assessed quantitatively using SNR, B0 field map, and B1 field map in a clinical 3T magnetic resonance imaging (MRI) scanner. Transcranial treatment using electronic focal steering was validated in red blood cell phantoms and in vivo pig brain through an excised human skull. In two pigs, targeted cerebral tissue was successfully treated through the human skull as confirmed by MRI. Excessive bleeding or edema was not observed in the peri-target zones by the time of pig euthanasia. These results demonstrated the feasibility of using this preclinical tcMRgHt system for in vivo transcranial treatment in a swine model.

Acoustic cavitation rheometry.

Characterization of soft materials is challenging due to their high compliance and the strain-rate dependence of their mechanical properties. The inertial microcavitation-based high strain-rate rheometry (IMR) method [Estrada et al., J. Mech. Phys. Solids, 2018, 112, 291-317] combines laser-induced cavitation measurements with a model for the bubble dynamics to measure local properties of polyacrylamide hydrogel under high strain-rates from 103 to 108 s-1. While promising, laser-induced cavitation involves plasma formation and optical breakdown during nucleation, a process that could alter local material properties before measurements are obtained. In the present study, we extend the IMR method to another means to generate cavitation, namely high-amplitude focused ultrasound, and apply the resulting acoustic-cavitation-based IMR to characterize the mechanical properties of agarose hydrogels. Material properties including viscosity, elastic constants, and a stress-free bubble radius are inferred from bubble radius histories in 0.3% and 1% agarose gels. An ensemble-based data assimilation is used to further help interpret the obtained estimates. The resulting parameter distributions are consistent with available measurements of agarose gel properties and with expected trends related to gel concentration and high strain-rate loading. Our findings demonstrate the utility of applying IMR and data assimilation methods with single-bubble acoustic cavitation data for measurement of viscoelastic properties.

Acoustic Measurements of Nucleus Size Distribution at the Cavitation Threshold.

An understanding of the acoustic cavitation threshold is essential for minimizing cavitation bio-effects in diagnostic ultrasound and for controlling cavitation-mediated tissue ablation in focused ultrasound procedures. The homogeneous cavitation threshold is an intrinsic material property of recognized importance to biomedical ultrasound as well as a variety of other applications requiring cavitation control. However, measurements of the acoustic cavitation threshold in water differ from those predicted by classic nucleation theories. This persistent discrepancy is explained by combining recently developed methods for acoustically nucleating single bubbles at threshold with numerical modeling to obtain a nucleus size distribution consistent with first-principles estimates for ion-stabilized nuclei. We identify acoustic cavitation at threshold as a reproducible subtype of heterogeneous cavitation with a characteristic nucleus size distribution. Knowledge of the nucleus size distribution could inspire new approaches to achieving cavitation control in water, tissue and a variety of other media.

A cost-effective, multi-flash, "ghost" imaging technique for high temporal and spatial resolution imaging of cavitation using "still-frame" cameras.

This paper describes a method for acquiring high temporal and spatial resolution images of cavitation events using a multiple-flash-per-camera-exposure imaging technique. A primary challenge associated with imaging cavitation is that the velocity of the bubble wall reaches its maximum (∼1.5×103 m/s) as the bubble size approaches its minimum (≲1 µm). In order to adequately resolve dynamics on these scales, specialized-often prohibitively expensive-cameras with ultra-high frame-rates and resolutions are generally required. This paper describes low-cost, high-speed light emitting diode (LED) flash sources with minimum pulse widths of 20 ns that can be pulsed at rates of up to 17 MHz. The flashes are used to illuminate images of bubbles captured using high-resolution "still-frame" cameras wherein multiple flashes are issued from the LED(s) at known time intervals within a single camera exposure, resulting in overlapping snapshots of the same bubble at multiple unique time-points in a single image. The overlapping snapshots can be uniquely associated with the known time-points of the flashes based on their relative levels brightness. This paper demonstrate effective frame-rates up to 4 Mfps using this technique and the acquisition of snapshots at up to 13 unique time-points per exposure. Hardware descriptions of the flash sources and the programmable device used to control them are provided.

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.

Histotripsy Clot Liquefaction in a Porcine Intracerebral Hemorrhage Model.

BACKGROUND: Intracerebral hemorrhage (ICH) is characterized by a 30-d mortality rate of 40% and significant disability for those who survive. OBJECTIVE: To investigate the initial safety concerns of histotripsy mediated clot liquefaction and aspiration in a porcine ICH model. Histotripsy is a noninvasive, focused ultrasound technique that generates cavitation to mechanically fractionate tissue. Histotripsy has the potential to liquefy clot in the brain and facilitate minimally invasive aspiration. METHODS: About 1.75-mL clots were formed in the frontal lobe of the brain (n = 18; n = 6/group). The centers of the clots were liquefied with histotripsy 48 h after formation, and the content was either evacuated or left within the brain. A control group was left untreated. Pigs underwent magnetic resonance imaging (MRI) 7 to 8 d after clot formation and were subsequently euthanized. Neurological behavior was assessed throughout. Histological analysis was performed on harvested brains. A subset of pigs underwent acute analysis (≤6 h). RESULTS: Histotripsy was able to liquefy the center of clots without direct damage to the perihematomal brain tissue. An average volume of 0.9 ± 0.5 mL was drained after histotripsy treatment. All groups showed mild ischemia and gliosis in the perihematomal region; however, there were no deaths or signs of neurological dysfunction in any groups. CONCLUSION: This study presents the first analysis of histotripsy-based liquefaction of ICH in vivo. Histotripsy safely liquefies clots without significant additional damage to the perihematomal region. The liquefied content of the clot can be easily evacuated, and the undrained clot has no effect on pig survival or neurological behavior.

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.

In vivo histotripsy brain treatment.

OBJECTIVE: Histotripsy is an ultrasound-based treatment modality relying on the generation of targeted cavitation bubble clouds, which mechanically fractionate tissue. The purpose of the current study was to investigate the in vivo feasibility, including dosage requirements and safety, of generating well-confined destructive lesions within the porcine brain utilizing histotripsy technology. METHODS: Following a craniectomy to open an acoustic window to the brain, histotripsy pulses were delivered to generate lesions in the porcine cortex. Large lesions with a major dimension of up to 1 cm were generated to demonstrate the efficacy of histotripsy lesioning in the brain. Gyrus-confined lesions were generated at different applied dosages and under ultrasound imaging guidance to ensure that they were accurately targeted and contained within individual gyri. Clinical evaluation as well as MRI and histological outcomes were assessed in the acute (≤ 6 hours) and subacute (≤ 72 hours) phases of recovery. RESULTS: Histotripsy was able to generate lesions with a major dimension of up to 1 cm in the cortex. Histotripsy lesions were seen to be well demarcated with sharp boundaries between treated and untreated tissues, with histological evidence of injuries extending ≤ 200 µm from their boundaries in all cases. In animals with lesions confined to the gyrus, no major hemorrhage or other complications resulting from treatment were observed. At 72 hours, MRI revealed minimal to no edema and no radiographic evidence of inflammatory changes in the perilesional area. Histological evaluation revealed the histotripsy lesions to be similar to subacute infarcts. CONCLUSIONS: Histotripsy can be used to generate sharply defined lesions of arbitrary shapes and sizes in the swine cortex. Lesions confined to within the gyri did not lead to significant hemorrhage or edema responses at the treatment site in the acute or subacute time intervals.

Soft-Tissue Aberration Correction for Histotripsy.

Acoustic aberrations caused by natural heterogeneities of biological soft tissue are a substantial problem for histotripsy, a therapeutic ultrasound technique that uses acoustic cavitation to mechanically fractionate and destroy unwanted target tissue without damaging surrounding tissue. These aberrations, primarily caused by sound speed variations, result in severe defocusing of histotripsy pulses, thereby decreasing treatment efficacy. The gold standard for aberration correction (AC) is to place a hydrophone at the desired focal location to directly measure phase aberrations, which is a method that is infeasible in vivo. We hypothesized that the acoustic cavitation emission (ACE) shockwaves from the initial expansion of inertially cavitating microbubbles generated by histotripsy can be used as a point source for AC. In this study, a 500-kHz, 112-element histotripsy phased array capable of transmitting and receiving ultrasound on all channels was used to acquire ACE shockwaves. These shockwaves were first characterized optically and acoustically. It was found that the shockwave pressure increases significantly as the source changes from a single bubble to a dense cavitation cloud. The first arrival of the shockwave received by the histotripsy array was from the outer-most cavitation bubbles located closest to the histotripsy array. Hydrophone and ACE AC methods were then tested on ex vivo porcine abdominal tissue samples. Without AC, the focal pressure is reduced by 49.7% through the abdominal tissue. The hydrophone AC approach recovered 55.5% of the lost pressure. Using the ACE AC method, over 20% of the lost pressure was recovered, and the array power required to induce cavitation was reduced by approximately 31.5% compared to without AC. These results supported our hypothesis that the ACE shockwaves coupled with a histotripsy array with transmit and receive capability can be used for AC for histotripsy through soft tissue.

Catheter Hydrophone Aberration Correction for Transcranial Histotripsy Treatment of Intracerebral Hemorrhage: Proof-of-Concept.

Histotripsy is a minimally invasive ultrasound therapy that has shown rapid liquefaction of blood clots through human skullcaps in an in vitro intracerebral hemorrhage model. However, the efficiency of these treatments can be compromised if the skull-induced aberrations are uncorrected. We have developed a catheter hydrophone which can perform aberration correction (AC) and drain the liquefied clot following histotripsy treatment. Histotripsy pulses were delivered through an excised human skullcap using a 256-element, 500-kHz hemisphere array transducer with a 15-cm focal distance. A custom hydrophone was fabricated using a mm PZT-5h crystal interfaced to a coaxial cable and integrated into a drainage catheter. An AC algorithm was developed to correct the aberrations introduced between histotripsy pulses from each array element. An increase in focal pressure of up to 60% was achieved at the geometric focus and 27%-62% across a range of electronic steering locations. The sagittal and axial -6-dB beam widths decreased from 4.6 to 2.2 mm in the sagittal direction and 8 to 4.4 mm in the axial direction, compared to 1.5 and 3 mm in the absence of aberration. After performing AC, lesions with diameters ranging from 0.24 to 1.35 mm were generated using electronic steering over a mm grid in a tissue-mimicking phantom. An average volume of 4.07 ± 0.91 mL was liquefied and drained after using electronic steering to treat a 4.2-mL spherical volume in in vitro bovine clots through the skullcap.

Effect of Frequency and Focal Spacing on Transcranial Histotripsy Clot Liquefaction, Using Electronic Focal Steering.

This in vitro study investigated the effects of ultrasound frequency and focal spacing on blood clot liquefaction via transcranial histotripsy. Histotripsy pulses were delivered using two 256-element hemispherical transducers of different frequency (250 and 500 kHz) with 30-cm aperture diameters. A 4-cm diameter spherical volume of in vitro blood clot was treated through 3 excised human skullcaps by electronically steering the focus with frequency proportional focal spacing: λ/2, 2 λ/3 and λ with 50 pulses per location. The pulse repetition frequency across the volume was 200 Hz, corresponding to a duty cycle of 0.08% (250 kHz) and 0.04% (500 kHz) for each focal location. Skull heating during treatment was monitored. Liquefied clot was drained via catheter and syringe in the range of 6-59 mL in 0.9-42.4 min. The fastest rate was 16.6 mL/min. The best parameter combination was λ spacing at 500 kHz, which produced large liquefaction through 3 skullcaps (23.1 ± 4.0, 37.1 ± 16.9 and 25.4 ± 16.9 mL) with the fast rates (3.2 ± 0.6, 5.1 ± 2.3 and 3.5 ± 0.4 mL/min). The temperature rise through the 3 skullcaps remained below 4°C.

Outcomes of the collapse of a large bubble in water at high ambient pressures.

Presented here are observations of the outcomes of the collapses of large single bubbles in H_{2}O and D_{2}O at high ambient pressures. Experiments were carried out in a high-pressure spherical resonator at ambient pressures of up to 30 MPa and acoustic pressures up to 35 MPa. Monitoring of the collapse events and their outcomes was accomplished using multiframe high-speed photography. Among the observations to be presented are the temporal and spatial evolution of light emissions produced by the collapse events, which were observed to last on the order of 30 ns and have time independent radii on the order of 30µm; the production of Rayleigh-Taylor jets which were observed to travel distances of up to 70µm at speeds in excess of 4500 m/s; the entrainment of the light emitting regions in the jets' remnants; the production of spheroidal objects around the collapse points of the bubbles, far from any surface of the resonator; and the traversal and emergence of the Rayleigh-Taylor jets through the spherical objects. These spheroidal objects appear to behave as amorphous solids and form at locations where hydrodynamics predicts pressures in excess of the known transition pressures of water into the high-pressure crystalline ices, Ice-VI and Ice-VII.