Acoustic Cavitation Emission Research Articles

Ultrasound-triggered in situ hydrogel formation for spinal disc repair

Over 600 million people suffer from lower back pain attributable to spinal disc degeneration. Treatments range from conservative physiotherapy to costly, invasive options like spinal fusion surgery. Injectable engineered materials may allow minimally invasive disc repair, but self-curing lacks process control, and optical in situ curing is depth-limited. We, therefore, propose ultrasound-triggered implant formation, enabling spatiotemporal control at clinically relevant tissue depths. We developed an anionic polysaccharide-based hydrogel, seeded with calcium-loaded thermosensitive liposomes. Focused ultrasound was used to heat this injectable precursor material to just above the lipid phase-transition temperature of 41 °C, inducing calcium release and ionically crosslinked network formation. Controlled heating was achieved by elevating the acoustic attenuation of the precursor solution with purified glass microspheres. The heating and gelation processes were controlled in real-time using thermometry and acoustic cavitation emissions. We optimized the ultrasound frequency and pressure amplitude to provide controlled heating with minimal cavitation. After these parameters were employed for ultrasound-mediated gelation, the rheological properties of the resultant gels were compared to literature values for native spinal disc material. Finally, in situ gel formation was evaluated in ex vivo bovine tail discs, from injection to mechanical assessments, confirming the ability to remotely trigger injectable disc-mimicking materials.

Active targeting of nanotherapeutics using power cavitation imaging with a linear array transducer

Power cavitation imaging (PCI) is an emerging strategy for monitoring blood–brain barrier (BBB) opening, enabling spatial discrimination of cavitation intensity through power Doppler-analogous processing of passive cavitation images. Single-element cavitation detectors, while beneficial in signal monitoring for cavitation controllers, provide limited spatial information, conferring the need for an image-guided approach to ensure accurate cavitation localization and regulation. This study aims to evaluate the capability of PCI to spatially correlate real-time acoustic cavitation emissions with mechanical bioeffects as a predictor of P-selectin-targeted nanocarrier delivery. Preliminary sonoporation experiments were performed in vitro with brain tissue derived mouse endothelial cells and 3 kDa tetramethylrhodamine (TMR)-dextran. A focused ultrasound transducer (0.5 MHz, 5000 cycles/pulse, 5 Hz PRF, 30 second treatment duration) was used to sonicate cells in small volume (25 μl) cell suspension. Homogenous distribution of TMR-dextran in the cytosol and nucleus was observed via fluorescence microscopy at lower pressures (7% ± 2% fluorescent cells), while higher pressures had no significant differences above control (3% ± 2% vs 1% nontreated) due to microbubble destruction. Future experiments will correlate sonoporation with P-selectin expression and validate a linear array PCI system against contrast-enhanced MRI as a guide for P-selectin-targeted nanocarrier delivery in mouse models of medulloblastoma.

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

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. 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. 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%. 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.

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

Acoustic cavitation emission (ACE)/shockwave signals generated by cavitation during histotripsy have been demonstrated to undergo characteristic changes correlated with the level of damage generated in select target media following repeated cavitation exposures, and may allow assessment of therapy-induced tissue damage during histotripsy. Here we investigate the impacts of nucleation medium on the evolutions of cavitation dynamics and ACE signals during repeated cavitation exposures. Repeated cavitation is generated in agarose, gelatin, and polyacrylamide hydrogels using a 700-kHz histotripsy array. High-speed imaging, broadband hydrophones, and histotripsy array elements are used to measure ACE signals and bubble dynamics. Bubble lifespans and collapse shockwave amplitudes were observed to be equivalent in optical and acoustic measurements. However, the evolutions of these properties, as well as bubble maximum radii, varied significantly across materials. Maximum radii initially increased and then decreased in agarose, but remained constant in gelatin and polyacrylamide. Lifespans increased monotonically in agarose and gelatin, but decreased in polyacrylamide. Collapse shockwave amplitudes evolved differently in all materials. The observed evolutions of the maximum radii, lifespans, and collapse shockwave amplitudes between media suggest that these features are dependent on the structure and stiffness of the nucleation medium and must be further investigated in tissues.

Acoustic cavitation localization during histotripsy using transmit-receive capable arrays

The nucleation and collapse of cavitation generated during histotripsy results in point-like emissions of shockwaves. Owing to the short duration acoustic pulses utilized during histotripsy the acoustic background from pulse reflections off intervening tissues is minimal and temporally isolated. This allows acoustic cavitation emission (ACE) shockwaves to be differentiated from the background in measured signals using simplified approaches such as peak detection and time gating, even in signals acquired using narrow bandwidth receivers such as the transmitting elements of the histotripsy array. The array elements allow acquisitions from across the array's entire aperture, which in turn allows cavitation to be localized in 3D. Here we describe multiple methods for localizing cavitation and evaluating induced tissue damage based on ACE signals measured using transmit-receive capable histotripsy arrays. The speed and accuracy of the methods were evaluated in ex vivo and in vitro experiments. Cavitation could be localized in 3D at rates >100Hz. Mean localization errors, with respect to measurements from optical images, were <2 mm (approximately the diameter of the generated bubbles). Cavitation lifespans could be assessed concurrently with the bubbles' 3D locations and correlated well with histological observations of induced damage, allowing 3D assessments of damage.

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.

Neuronavigation-guided transcranial histotripsy, results in a cadaveric model

Results from neuronavigation-guided transcranial histotripsy treatments in cadaveric models are presented. Histotripsy treatments were delivered transcranially to the brains of 3 cadavers (<96-h post-mortem) using a 30-cm diameter, 700-kHz, 360-element, transmit-receive capable transcranial histotripsy array. Pre-treatment CT and MRI scans of the head were acquired. A clinical neuronavigation system was used to coregister the histotripsy array with the cadaver head and guide treatments. Two-step aberration correction, combining pre-treatment CT-based correction and intra-procedure acoustic cavitation emission (ACE)-based correction, was employed to correct for skull-induced acoustic aberrations. Cavitation was generated at rates up to 200-Hz, and steered through 1-cm wide cubic targets in the brain. ACE signals were acquired throughout treatments using the array elements as receivers and used to localize cavitation and monitor treatment.Transcranial histotripsy was successfully applied to generate lesions in the cadaver brains. Two-step aberration correction resulted in significant improvements in focal quality and pressure. ACE-based cavitation localization could be achieved at rates up to 120-Hz. Neuronavigation-based coregistration/targeting errors ranged from 3 to 9-mm, but workflow issues have been identified and refinements have since reduced targeting errors to ≤1.5-mm. Changes in ACE signal features throughout treatments were observed to correlate with morphological observations of induced damage.

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 mm3 on 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.

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.

Real-time visualization of instantaneous frequency from bubble cavitation using color Doppler ultrasound imaging

Time-resolved observations of acoustic cavitation emission signals are important in understanding bubble cavitation dynamics and monitoring sonoporation efficiencies of ultrasound-assisted drug delivery systems. Previous methods using back propagation of such signals measure frequencies with high time resolutions but require post-processing. We propose a method using color Doppler ultrasound to obtain instantaneous frequencies of these signals from the phase differences with an external reference signal. Standard color Doppler processing is applied to both emissions and reference signals to enable real-time observations of bubble cavitation generated by high-intensity ultrasound wave irradiation. A sinusoidal wave signal was used to confirm the accuracy of our method with an estimation error of 8.59%. Experiments were performed using Sonazoid suspensions of two different concentrations. With a sound pressure of 1.0 MPa for the ultrasound wave, the type of bubble cavitation that is dominant is different before and after irradiation of about ten pulses.

Observing Bubble Cavitation by Back-Propagation of Acoustic Emission Signals.

Temporal- and spatial-resolved observations of microbubble cavitation generated through high-intensity ultrasound irradiation are key in improving both the efficiency and efficacy of ultrasound-assisted drug delivery systems. A method of measuring bubble cavitation applying an image-reconstruction technique of back-propagation of an acoustic cavitation emission (ACE) signal is proposed. A high-intensity focused ultrasound wave (pump wave) irradiates the bubble synchronously using ultrasound recording equipment to acquire the timing of the RF signal, which is produced when the bubble radiates a secondary wave during bubble cavitation. The ACE signal source is reconstructed through ultrasound-wave back-propagation followed by amplitude deconvolution. The proposed method was applied to microbubbles of an ultrasound contrast agent by changing the sound pressure of the pump wave. The method reliability of the temporal resolution was verified by simulating the amplitude-modulated signal of the virtual sound source. The temporal transition of the ACE signal exhibited sub-microsecond-order fluctuations in the signal intensity. From the amplitude signal image and the instantaneous frequency image reconstruction of the proposed method, two different ACE phenomena were visualized. One is the periodic pattern by the beat signals from the harmonic and ultraharmonic component of nonlinear oscillation under low-intensity ultrasound conditions. The other is the nonperiodic temporal and spatial distributions of this irradiation under high-intensity ultrasound conditions.

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.

Power cavitation-guided blood-brain barrier opening with focused ultrasound and microbubbles

Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies relies on the accurate localization of FUS-stimulated microbubble activity (i.e. acoustic cavitation). Passive cavitation imaging with ultrasound arrays can achieve this, but with insufficient spatial resolution. In this study, we address this limitation and perform high-resolution monitoring of acoustic cavitation-mediated blood-brain barrier (BBB) opening with a new technique called power cavitation imaging. By synchronizing the FUS transmit and passive receive acquisition, high-resolution passive cavitation imaging was achieved by using delay and sum beamforming with absolute time delays. Since the axial image resolution is now dependent on the duration of the received acoustic cavitation emission, short pulses of FUS were used to limit its duration. Image sets were acquired at high-frame rates for calculation of power cavitation images analogous to power Doppler imaging. Power cavitation imaging displays the mean intensity of acoustic cavitation over time and was correlated with areas of acoustic cavitation-induced BBB opening. Power cavitation-guided BBB opening with FUS could constitute a standalone system that may not require MRI guidance during the procedure. The same technique can be used for other acoustic cavitation-based FUS therapies, for both safety and guidance.

Transcranial acoustic cavitation localization with ultrafast power cavitation imaging in non-human primates

Acoustic cavitation-guided blood-brain barrier (BBB) opening with focused ultrasound (FUS) and microbubbles is a promising technique for safe and controlled opening of the BBB. Passive cavitation imaging has the ability to monitor the spatial intensity of acoustic cavitation for targeting verification and treatment monitoring. However, isolating acoustic cavitation emissions from tissue and skull reflections is a major challenge. In this study, we perform transcranial passive cavitation imaging with a 1.5D imaging array (M5Sc-D, bandwidth: 1.5–4 MHz, GE Medical Systems) placed in the central opening of a 0.5 MHz FUS transducer (H204, Sonic Concepts) in non-human primates. Broadband FUS pulses were used along with synchronous transmit and receive sequences to perform delay and sum beamforming with absolute time delays. Image sets were acquired at ultrafast frame rates (>1000 frames per second) for calculation of mean intensity images, i.e., power cavitation images. Spatiotemporal clutter filtering of image...

Correlating Inertial Acoustic Cavitation Emissions with Material Erosion Resistance

The standard ASTM G32-10 concerns the hydrodynamic cavitation erosion resistance of materials by subjecting them to acoustic cavitation generated by a sonotrode. The work reported extends this technique by detecting and monitoring the ultrasonic cavitation, considered responsible for the erosion process, specifically for coupons of aluminium-bronze alloy. The study uses a 65mm diameter variant of NPL's cavitation sensor, which detects broadband acoustic emissions, and logs acoustic signals generated in the MHz frequency range, using NPL's Cavimeter. Cavitation readings were made throughout the exposure duration, which was carried out at discrete intervals (900 to 3600 s), allowing periodic mass measurements to be made to assess erosion loss under a strict protocol.Cavitation measurements and erosion were compared for different separations of the sonotrode tip from the material under test. The maximum variation associated with measurement of cavitation level was between 2.2% and 3.3% when the separation (λ) between the transducer horn and the specimen increased from 0.5 to 1.0mm, for a transducer (sonotrode) displacement amplitude of 43.5μm. Experiments conducted at the same transducer displacement amplitude show that the mass loss of the specimen —a measure of erosion— was 67.0mg (λ = 0.5mm) and 66.0mg (λ = 1.0mm).

Effects of the microbubble shell physicochemical properties on ultrasound-mediated drug delivery to the brain

Lipid-shelled microbubbles have been used in ultrasound-mediated drug delivery. The physicochemical properties of the microbubble shell could affect the delivery efficiency since they determine the microbubble mechanical properties, circulation persistence, and dissolution behavior during cavitation. Therefore, the aim of this study was to investigate the shell effects on drug delivery efficiency in the brain via blood–brain barrier (BBB) opening in vivo using monodisperse microbubbles with different phospholipid shell components. The physicochemical properties of the monolayer were varied by using phospholipids with different hydrophobic chain lengths (C16, C18, and C24). The dependence on the molecular size and acoustic energy (both pressure and pulse length) were investigated. Our results showed that a relatively small increase in the microbubble shell rigidity resulted in a significant increase in the delivery of 40-kDa dextran, especially at higher pressures. Smaller (3kDa) dextran did not show significant difference in the delivery amount, suggesting that the observed shell effect was molecular size-dependent. In studying the impact of acoustic energy on the shell effects, it was found that they occurred most significantly at pressures causing microbubble destruction (450kPa and 600kPa); by increasing the pulse length to deliver the 40-kDa dextran, the difference between C16 and C18 disappeared while C24 still achieved the highest delivery efficiency. These indicated that the acoustic energy could be used to modulate the shell effects. The acoustic cavitation emission revealed the physical mechanisms associated with different shells. Overall, lipid-shelled microbubbles with long hydrophobic chain length could achieve high delivery efficiency for larger molecules especially with high acoustic energy. Our study, for the first time, offered evidence directly linking the microbubble monolayer shell with their efficacy for drug delivery in vivo.

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue.

Ultrasound-mediated drug delivery is a novel technique for enhancing the penetration of drugs into diseased tissue beds noninvasively. By encapsulating drugs into microsized and nanosized liposomes, the therapeutic can be shielded from degradation within the vasculature until delivery to a target site by ultrasound exposure. Traditional in vitro or ex vivo techniques to quantify this delivery profile include optical approaches, cell culture, and electrophysiology. Here, we demonstrate an approach to characterize the degree of nitric oxide (NO) delivery to porcine carotid tissue by direct measurement of ex vivo vascular tone. An ex vivo perfusion model was adapted to assess ultrasound-mediated delivery of NO. This potent vasodilator was coencapsulated with inert octafluoropropane gas to produce acoustically active bubble liposomes. Porcine carotid arteries were excised post mortem and mounted in a physiologic buffer solution. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded bubble liposomes were infused into the lumen of the artery, which was exposed to 1 MHz pulsed ultrasound at a peak-to-peak acoustic pressure amplitude of 0.34 MPa. Acoustic cavitation emissions were monitored passively. Changes in vascular tone were measured and compared with control and sham NO bubble liposome exposures. Our results demonstrate that ultrasound-triggered NO release from bubble liposomes induces potent vasorelaxation within porcine carotid arteries (maximal relaxation 31%±8%), which was significantly stronger than vasorelaxation due to NO release from bubble liposomes in the absence of ultrasound (maximal relaxation 7%±3%), and comparable with relaxation due to 12 μM sodium nitroprusside infusions (maximal relaxation 32%±3%). This approach is a valuable mechanistic tool for assessing the extent of drug release and delivery to the vasculature caused by ultrasound.

Ultrasound-mediated delivery of bioactive nanobubbles to vascular tissue

Bubble liposomes (BLs) are under development for ultrasound-triggered release of a potent vasodilator within the vasculature. Nano-sized vesicles facilitate this process by enclosing bubbles to enhance ultrasound image contrast, and deliver therapeutic agents. Assessment of drug delivery in living tissue allows for mechanistic pathways to be revealed. In this study, we used a novel ex vivo model to assess the vascular effects of ultrasound-mediated delivery of a bioactive gas-nitric oxide (NO)-from nanobubble liposomes. Porcine carotid arteries were excised post-mortem and mounted in physiologic buffer. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded BLs were infused into the lumen of the artery, which was exposed to 1-MHz pulsed ultrasound, while acoustic cavitation emissions were monitored. Changes in vascular tone were concurrently measured and compared to control and sham NO exposures. Our results demonstrate that ultrasound-triggered NO release from BLs induces potent vasorelaxation within porcine carotid arteries. This approach is a valuable mechanistic tool to assess the bioeffects that NO elicits within the vasculature upon release from BLs exposed to 1-MHz ultrasound.

An experimental system for the study of ultrasound exposure of isolated blood vessels

An experimental system designed for the study of the effects of diagnostic or therapeutic ultrasound exposure on isolated blood vessels in the presence or absence of intraluminal contrast agent is described. The system comprised several components. A microscope was used to monitor vessel size (and thus vessel functionality), and potential leakage of intraluminal 70 kDa FITC-dextran fluorescence marker. A vessel chamber allowed the mounting of an isolated vessel whilst maintaining its viability, with pressure regulation for the control of intraluminal pressure and induction of flow for the infusion of contrast microbubbles. A fibre-optic hydrophone sensor mounted on the vessel chamber using a micromanipulator allowed pre-exposure targeting of the vessel to within 150 µm, and monitoring of acoustic cavitation emissions during exposures. Acoustic cavitation was also detected using changes in the ultrasound drive voltage and by detection of audible emissions using a submerged microphone. The suitability of this system for studying effects in the isolated vessel model has been demonstrated using a pilot study of 6 sham exposed and 18 high intensity focused ultrasound exposed vessels, with or without intraluminal contrast agent (SonoVue) within the vessels.

Spatio-temporal mapping and characterization of acoustic cavitation seeded by microbubbles and solid microparticles during focused ultrasound exposure

Cavitation nuclei are often used to seed and promote acoustic cavitation in therapeutic applications. However, the effects of fluid velocity and ultrasound exposure parameters peak rarefactional pressure (Pr), pulse duration (PD), and pulse repetition frequency (PRF) on the spatial distribution, type, magnitude, and number of acoustic cavitation events for each nuclei remains poorly understood. In this study, a 1.6-mm diameter tunnel phantom (3% agar) was perfused (fluid velocity: 10–40 mm/s) with either microbubbles (SonoVue) or hydrophobic solid microparticles (TALC) and exposed to 74 different acoustic parameter combinations (frequency: 0.5 MHz, Pr: 150–1500 kPa, PD: 1–100,000 cycles, PRF: 1–50 Hz, number of pulses: 10–250). Spatial mapping of passively acquired acoustic cavitation emissions was performed with a 64-element array coaxial to the focused ultrasound transducer. At pressures above the cavitation threshold, cavitation activity generated from microbubbles was significantly reduced and spatially biased upstream after the first pulse at high PRFs relative to the fluid velocity. On the other hand, solid microparticles had no spatial bias and no significant reduction in the energy of acoustic emissions after the first pulse. Whereas microbubbles may be destroyed, and therefore, cease to act as cavitation nuclei, solid microparticles do not suffer from depletion of energy with high PRFs.