Jamie Collin

Passive acoustic mapping of magnetic microbubbles for cavitation enhancement and localization.

Magnetic targeting of microbubbles functionalized with superparamagnetic nanoparticles has been demonstrated previously for diagnostic (B-mode) ultrasound imaging and shown to enhance gene delivery in vitro and in vivo. In the present work, passive acoustic mapping (PAM) was used to investigate the potential of magnetic microbubbles for localizing and enhancing cavitation activity under focused ultrasound. Suspensions of magnetic microbubbles consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), air and 10 nm diameter iron oxide nanoparticles were injected into a tissue mimicking phantom at different flow velocities (from 0 to 50 mm s(-1)) with or without an applied magnetic field. Microbubbles were excited using a 500 kHz single element focused transducer at peak negative focal pressures of 0.1-1.0 MPa, while a 64 channel imaging array passively recorded their acoustic emissions. Magnetic localization of microbubble-induced cavitation activity was successfully achieved and could be resolved using PAM as a shift in the spatial distribution and increases in the intensity and sustainability of cavitation activity under the influence of a magnetic field. Under flow conditions at shear rates of up to 100 s(-1) targeting efficacy was maintained. Application of a magnetic field was shown to consistently increase the energy of cavitation emissions by a factor of 2-5 times over the duration of exposures compared to the case without targeting, which was approximately equivalent to doubling the injected microbubble dose. These results suggest that magnetic targeting could be used to localize and increase the concentration of microbubbles and hence cavitation activity for a given systemic dose of microbubbles or ultrasound intensity.

Attenuation and De-focusing During High-Intensity Focused Ultrasound Therapy Through Peri-nephric Fat

High-intensity focused ultrasound (HIFU) is an attractive therapy for kidney cancer, but its efficacy can be limited by heat deposition in the pre-focal tissues, notably in fat around the kidney (peri-nephric fat), the acoustic properties of which have not been well characterized. Measurements of attenuation were made using a modified insertion-loss technique on fresh, unfixed peri-nephric fat obtained from patients undergoing kidney surgery for cancer. The de-focusing effect of changing the position of the fat layers was also investigated using fresh subcutaneous fat from euthanized pigs. The mean attenuation of human peri-nephric fat was found to be 11.9 ± 0.9 Np/m (n = 10) at 0.8 MHz, the frequency typically used for HIFU ablation of kidney tumors, with a frequency dependence of f(1.2). A typical 2- to 4-cm thickness of peri-nephric fat would result in a de-rated intensity of 3% - 62% at 0.8 MHz compared with a hypothetical patient with no peri-nephric fat. Through the use of freshly excised porcine subcutaneous fat, the presence of fat 100 mm in front of the focus was found to have a de-focusing effect of approximately 1 mm in both transverse directions, which corresponds to a full HIFU beam width off-target. Peri-nephric fat may significantly affect both the intensity and accuracy of HIFU fields used for the ablation of kidney cancer.

Quantitative observations of cavitation activity in a viscoelastic medium

Quantitative experimental observations of single-bubble cavitation in viscoelastic media that would enable validation of existing models are presently lacking. In the present work, single bubble cavitation is induced in an agar gel using a 1.15 MHz high intensity focused ultrasound transducer, and observed using a focused single-element passive cavitation detection (PCD) transducer. To enable quantitative observations, a full receive calibration is carried out of a spherically focused PCD system by a bistatic scattering substitution technique that uses an embedded spherical scatterer and a hydrophone. Adjusting the simulated pressure received by the PCD by the transfer function on receive and the frequency-dependent attenuation of agar gel enables direct comparison of the measured acoustic emissions with those predicted by numerical modeling of single-bubble cavitation using a modified Keller-Miksis approach that accounts for viscoelasticity of the surrounding medium. At an incident peak rarefactional pressure near the cavitation threshold, period multiplying is observed in both experiment and numerical model. By comparing the two sets of results, an estimate of the equilibrium bubble radius in the experimental observations can be made, with potential for extension to material parameter estimation. Use of these estimates yields good agreement between model and experiment.

Non‐Invasive Monitoring and Control of Inertial Cavitation Dynamics during HIFU Exposure In Vitro

Inertial cavitation has been shown to play a significant role in enhancing HIFU ablation, especially when the focal temperatures do not exceed 100 degrees. However, once cavitation is instigated, the bubble cloud grows unstably towards the HIFU transducer, shielding the original focus. In this study, a passive cavitation detection (PCD) technique was used to monitor inertial cavitation activity during 1.1‐MHz CW exposure of an agar‐graphite tissue mimicking material for peak‐negative focal pressures in the range 1.84–4.98 MPa. In all cases, the RMS time trace of the PCD signal exhibited a plateau region of some 3 seconds, followed by an extremely sharp peak, beyond which a rapid decay in broadband noise emissions was observed. No significant increase in broadband noise was induced for HIFU amplitudes in excess of 3.42 MPa, which suggests that the heating enhancement provided by cavitation saturates beyond that peak negative pressure amplitude. Based on these results, the use of pulsed excitation was investigated as a means of controlling cavitation activity following a brief period of CW exposure. Cavitation activity was readily sustained in the focal region for periods in excess of 60 s in all cases. However, the level of sustained activity was found to be highest for 20% duty cycle, and lower for 10% and 40 % duty cycle. It is concluded that pulsed HIFU excitation can be used to sustain and confine cavitation activity to the focal region, and that RMS analysis of PCD signals provides a very robust descriptor of bubble cloud dynamics.

Real-time three-dimensional passive cavitation detection for clinical high intensity focused ultrasound systems

Bubble activity during High Intensity Focussed Ultrasound (HIFU) surgery has been linked with desirable effects, such as an enhanced heat deposition caused by inertial cavitation, and undesirable effects, such as lesion migration caused by boiling bubbles. There is presently no reliable way of achieving spatiotemporal monitoring of cavitation activity during clinical HIFU treatments. In the present work, a near-acoustically- transparent two-dimensional 32-element PVDF array was designed and mounted on the therapy transducer of a clinical HIFU device (Model JC200, Chongqing Haifu) to enable detection of acoustic emissions arising from cavitation during therapy. The signal detected by each of the elements was digitized and processed in real time on a Graphical Processing Unit (GPU), and beamformed using our previously described Passive Acoustic Mapping (PAM) algorithm to produce real-time three-dimensional (3D) maps of cavitation activity with a frame rate in excess of 5 Hz. The system was initially validated in agar-based tissue-mimicking materials, demonstrating that the displayed volume of cavitation activity agreed with predictions based on in situ pressure calibrations. The system was further validated during clinical HIFU treatments of kidney tumour, liver tumour and uterine fibroid ablation, and was found to enable accurate localization of the HIFU focus at sub-lesioning intensities.

Passive acoustic mapping of stable and inertial cavitation during ultrasound therapy

Accurate spatio-temporal characterization, quantification, and control of the type and extent of cavitation activity is crucial for a wide range of therapeutic ultrasound applications, ranging from ablation to sonothrombolysis, opening of the blood-brain barrier and drug delivery for cancer. Passive Acoustic Mapping (PAM) is a technique that utilizes arrays of acoustic detectors, typically coaxially aligned or coincident with the therapeutic elements, to receive acoustic emissions outside the main frequency band of the therapy pulse. The signals received by each detector are then filtered in the frequency domain into harmonics and ultra/subharmonics of the fundamental therapeutic frequency and other broadband components, and subsequently beamformed using a multi-correlation algorithm, which uses measures of similarity between the signals rather than time-of-flight information in order to map sources of non-linear emissions in real time. 2D and 3D cavitation maps obtained using time exposure acoustics beam...

Significant skin burns may occur with the use of a water balloon in HIFU treatment

HIFU is a minimally-invasive therapy suitable for treating selected intra-abdominal tumors. Treatment is safe although skin burns may occur due to pre-focal heating. HIFU treatment of a renal transplant tumor located in the left lower abdomen was undertaken in our centre. Treatment was performed prone, requiring displacement of the abdominal wall away from the treatment field using a water balloon, constructed of natural rubber latex and filled with degassed water. Intra-operatively, ultrasound imaging and physical examination of the skin directly over the focal region was normal. Immediately post-operative, a full-thickness skin burn was evident at the periphery of the balloon location, outside the expected HIFU path. Three possibilities may account for this complication. Firstly, the water balloon may have acted as a lens, focusing the HIFU to a neo-focus off axis. Secondly, air bubbles may have been entrapped between the balloon and the skin, causing heating at the interface. Finally, heating of the is...

In vitro validation of three‐dimensional cavitation‐based pressure mapping for quality assessment of clinical high intensity focused ultrasound devices.

Sufficiently robust and reliable quality assessment (QA) procedures are vital in assuring the widespread adoption of high intensity focused ultrasound (HIFU) for use in both thermal ablation and enhanced drug delivery. Mapping of broadband cavitation emissions in a tissue‐mimicking material with a repeatable cavitation threshold offers the potential for rapid, 3‐D, cavitation‐based pressure mapping of the field produced by a given HIFU transducer. Previous work has demonstrated the viability of this concept, including the design and optimization of a 50‐element, cylindrical array capable of mapping a collection of broadband sources distributed throughout a region comparable to the size of a typical HIFU focal volume. The work presented here relates to in vitro experimentation using the array to map cavitating fields produced by a number of HIFU transducers at a range of insonation amplitudes. Results are compared to the predicted size of the cavitation region determined via hydrophone‐based characterizati...

Three‐dimensional passive localization of cavitation activity for quality assessment of clinical high‐intensity focused ultrasound devices.

The widespread adoption of high‐intensity focused ultrasound (HIFU) as a modality for non‐invasive treatment of malignant tissue will rely heavily on the implementation of robust and reliable quality assessment (QA) procedures. Previous work has demonstrated the viability of using cavitation emissions as a QA tool for rapid mapping of the acoustic fields generated by HIFU transducers. The present work details the design, implementation, and experimental validation of a cylindrical array surrounding the HIFU focus for 3‐D passive mapping of cavitating fields produced by clinical HIFU transducers. The configuration of array elements was first optimized for accurate mapping of cavitation activity both on‐axis and off‐axis by modeling the received signal from a collection of broadband sources. A novel 50‐element array was subsequently manufactured from PVDF using a novel printed circuit board technique. Testing of the array has been conducted by mapping the extent and evolution of the cavitation field produce...

Design and implementation of a cylindrical array for passive mapping of cavitation fields produced by clinical high intensity focused ultrasound transducers.

Key to the success of high‐intensity focused ultrasound (HIFU) as a clinical tool is the development of standardized quality assessment procedures to assess the safety and efficacy of HIFU transducers. The present work details the development of a cylindrical sensor array to be positioned around the HIFU focus during pre‐treatment quality assessment of clinical transducers, which is designed to localize cavitation activity in three dimensions by passive mapping of the broadband emissions arising from inertial cavitation. The propagation of sound from a collection of broadband sources was first modeled to determine the optimum size, number and distribution of array elements for accurate mapping, and characterization of the cavitation dynamics produced during HIFU exposure. The optimal array configuration was then manufactured from PVDF using a novel printed circuit board technique, and theoretical predictions of the spatial resolution that it could achieve were validated experimentally. Because inertial ca...