Power Of High-intensity Focused Ultrasound Research Articles

Effect of difference in shear modulus of biological tissue on heat source distribution of high-intensity focused ultrasound estimated by acoustic radiation force imaging

High-intensity focused ultrasound (HIFU) is a novel noninvasive cancer treatment that is expected to be a potential alternative to conventional therapies. In the treatment, the accurate prediction of the ultrasonic heat source prior to therapeutic exposure is important for safety and efficacy. Acoustic radiation force imaging using a short HIFU burst has been proposed as a method for this prediction from the distribution of the tissue displacement. In this study, the effect of the difference in shear modulus on the estimation of the HIFU heat source was experimentally investigated by applying the imaging method to different biological tissues: chicken breast and chicken liver tissues. The result suggested that HIFU radiation force imaging has the potential to determine the HIFU power for appropriate treatment quantitatively from the displacement, even in different tissues with different shear moduli.

Experimental study of water/tissue conductivity variation under 1 MHz HIFU radiation

High Intensity Focused Ultrasound (HIFU) has long demonstrated its effectiveness and advantage on tumor treatment, drug delivery, and some other therapies. In order to efficiently and accurately control HIFU, HIFU monitoring technology became critical. B-type scan or MRI are the two kinds of effective ways to monitor HIFU. While B-type scan has to interleave with HIFU to avoid white noise on the B-scan images, the MRI is expensive and bulky, not an ideal way to monitor HIFU either. This paper presents research to explore the possibility to monitor HIFU via impedance/resistance property. The theoretical analysis, the experimental setup and results with water phantom and two kinds of tissue holders are presented. The experimental results show that the resistance value changes instantaneously at the moment the HIFU is turned on/off and the magnitude of the resistance change is proportional to the square root of HIFU power, which indicates that the resistance property could be an effective way to monitor the existence and the power level of HIFU. The resistance is sensitive to the temperature variation and the formation of lesions as well. More research with ex vivo and in vivo experiments at different HIFU frequencies and power levels are strongly suggested to investigate the detailed mechanisms of the resistance change during HIFU and hence further clearly specify the way to monitor HIFU via resistance measurement.

HIFU Power Monitoring Using Combined Instantaneous Current and Voltage Measurement.

During high-intensity focused ultrasound (HIFU) therapy, it is important that the electrical power delivered to the transducer is monitored to avoid underexposure or overexposure, ensure patient safety, and to protect the transducer itself. Due to ease of measurement, the transducer's potential difference may be as an indicator of power delivery. However, even when a transducer's complex impedance is well characterized at small amplitudes and matching networks are used, voltage-only (VO) monitoring cannot account for the presence of drive waveform distortion, changes to the acoustic path, or damage to the transducer. In this study, combined current and voltage (CCV) is proposed as a magnetic resonance imaging (MRI)-compatible, miniature alternative to bidirectional power couplers, which is compatible with switched amplifiers. For CCV power measurement, current probe data were multiplied by the voltage waveform and integrated in the frequency domain. Transducer efficiency was taken into account to predict acoustic power. The technique was validated with a radiation force balance (RFB). When using a typical HIFU transducer and amplifier, VO predictions and acoustic power had a maximum difference of 20%. However, under the same conditions, CCV only had a maximum difference of 5%. The technique was applied to several lesioning experiments and it was shown that when VO was used as a control between two amplifiers, there was up to a 38% difference in lesion area. This greatly reduced to a maximum of 5% once CCV was used instead. These results demonstrate that CCV can accurately predict real-time electrical power delivery, leading to safer HIFU treatments.

Self-Scanned HIFU Ablation of Moving Tissue Using Real-Time Hybrid US-MR Imaging.

High intensity focused ultrasound (HIFU) treatment in the abdominal cavity is challenging due to the respiratory motion. In the self-scanning HIFU ablation method, the focal spot is kept static and the heating pattern is obtained through natural tissue motion. This paper describes a novel approach for modulating the HIFU power during self-scanning in order to compensate for the effect of tissue motion on thermal buildup. The therapy, using hybrid ultrasound (US)/magnetic resonance (MR) imaging, consists of detecting and tracking speckle on US images in order to predict the next tissue position, and modulating the HIFU power according to the tissue speed in order to obtain a rectilinear pattern of uniform temperature elevation. Experiments were conducted on ex vivo tissue subjected to a breathing-like motion generated by an MR-compatible robot and sonicated by a phased array HIFU transducer. US and MR data were free from interferences. For both periodic and non-periodic motion, MR temperature maps showed a substantial improvement in the uniformity of the temperature elevation by using acoustic power modulation. The presented method does not require a learning stage and enables a duty cycle close to 100%, higher average acoustic intensity and avoidance of side lobe effects versus performing HIFU beam steering to compensate tissue motion. To our knowledge, the proposed method provides the first experimental validation of the self-scanning HIFU ablation paradigm via a real-time hybrid MRI/US imaging, opening the path toward self-scanning in vivo therapies.

Quantitative measurement and real-time tracking of high intensity focused ultrasound using phase-sensitive optical coherence tomography: Feasibility study

Purpose: Phase-sensitive optical coherence tomography (PhS-OCT) is proposed, as a new high intensity focused ultrasound (HIFU) imaging guidance to detect and track HIFU focus inside 1% agar samples in this work. The experiments studied the effect of varying HIFU power on the induction of shear wave, which can be implemented as a new technique to monitor focused ultrasound surgery (FUS).Method: A miniature HIFU transducer (1.02 MHz, 20 mm aperture diameter, 15 mm radius of curvature) was produced in-house, pressure-field mapped, and calibrated. The transducer was then embedded inside a 1% agar phantom, which was placed under PhS-OCT for observation, under various HIFU power settings (acoustic power, and number of cycles per pulse). Shear wave was induced on the sample surface by HIFU and was captured in full under PhS-OCT. The lowest HIFU acoustic power output for the detection of shear wave was found to be 0.36 W (1.02 MHz, 100 cycles/pulse), or with the number of cycles/pulse as low as 20 (1.02 MHz, 0.98 W acoustic power output).Results: A linear relationship between acoustic power output and the maximum shear wave displacement was found in the first study. The second study explores a non-linear correlation between the (HIFU) numbers of cycles per pulse, and the maximum shear wave displacement.Conclusion: PhS-OCT demonstrates excellent tracking and detection of HIFU-induced shear wave. The results could benefit other imaging techniques in tracking and guiding HIFU focus. Further studies will explore the relationship between the physical transducer characteristics and the HIFU-induced shear wave.

Targeted ultrathin silica nanoshells as HIFU sensitizing agents for in vivo LnCAP prostate tumor removal

Event Abstract Back to Event Targeted ultrathin silica nanoshells as HIFU sensitizing agents for in vivo LnCAP prostate tumor removal James Wang1, Alexander Liberman2, Christopher Barback3, Sarah L. Blair4, Robert F. Mattrey3, William C. Trogler5 and Andrew C. Kummel5 1 University of California San Diego, Nanoengineering, United States 2 University of California San Diego, Material Science and Engineering, United States 3 University of California San Diego, Radiology, United States 4 University of California San Diego, Moores Cancer Center, United States 5 University of California San Diego, Chemistry and Biochemistry, United States Diagnostic ultrasound (US) is a prevalent medical imaging modality due to its low-cost, high resolution, and therapeutic capability when coupled with high intensity focused ultrasound (HIFU) systems. 500 nm rigid silica ultrathin nanoshells were synthesized as a chemically stable US tumor marking contrast agent with continuous in vivo US imaging lifetime. Iron (III) was included into the silica shell network to promote biodegradability from serum transferrin proteins. It was shown previously that the removal of iron from the silica shell network via transferrin fragments the nanoshells for effective biodegradation. Folate was conjugated to the surface of the silica nanoshells via the 3-aminopropyltriethoxysilane (APTES) linker. Folate has been shown in the literature to bind to prostate specific membrane antigen (PSMA) with a high binding affinity due to folate hydrolase activity. Conjugating the silica nanoshell surface with folate targets the ultrathin silica nanoshells towards the LnCAP tumor where PSMA is significantly up-regulated. The surface modified ultrathin silica nanoshells were filled with liquid perfluorocarbon (PFC) which underwent acoustic droplet vaporization (ADV) during US insonation. The phase transition of PFC from liquid to vapor generated a large amount of PFC microbubbles that created contrast during US imaging. In vitro experiments with US have demonstrated that the ultrathin silica nanoshells can be imaged for at least 3 hours under color Doppler imaging, exhibiting a continuous US imaging lifetime. In vivo experiments have shown that folate conjugated silica nanoshells were able to accumulate and persist within the tumor region for up to 12 days post-injection, observable with US imaging. Surface conjugation with polyethylene glycol (PEG) increased the ultrasound signal at the tumor by increasing the particles accumulating at the tumor site. When exposed to high intensity focused ultrasound (HIFU), the particles were able to enhance the HIFU power and liquefy tumor tissue. With particles present, the HIFU duty cycle can be lowered to 2 %, minimizing tissue thermal deposition. By synthesizing ultrathin silica nanoshells with a folate-conjugated surface, it is has been demonstrated that folate-conjugated ultrathin rigid silica nanoshells can accumulate in the LnCAP tumor persistently for 12 days. PEGylation of the particles further increase the particle accumulation concentration in the tumor, acting as a HIFU sensitizing agent for ultrasound histotripsy. Through intelligent surface modification, liquid PFC filled silica particles can act as a multi-functional theranostic agent for ultrasound diagnosis. Keywords: contrast agent, nanoparticle, targeting delivery Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Imaging with biomaterials Citation: Wang J, Liberman A, Barback C, Blair SL, Mattrey RF, Trogler WC and Kummel AC (2016). Targeted ultrathin silica nanoshells as HIFU sensitizing agents for in vivo LnCAP prostate tumor removal. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00236 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers James Wang Alexander Liberman Christopher Barback Sarah L Blair Robert F Mattrey William C Trogler Andrew C Kummel Google James Wang Alexander Liberman Christopher Barback Sarah L Blair Robert F Mattrey William C Trogler Andrew C Kummel Google Scholar James Wang Alexander Liberman Christopher Barback Sarah L Blair Robert F Mattrey William C Trogler Andrew C Kummel PubMed James Wang Alexander Liberman Christopher Barback Sarah L Blair Robert F Mattrey William C Trogler Andrew C Kummel Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Effects of contrast agents and high intensity focused ultrasound on tumor vascular perfusion

High intensity focused ultrasound (HIFU) is a treatment modality which causes localized tissue ablation and is further enhanced when microbubble or nanodroplet contrast agents are present. While it is known that HIFU ablation results in diminished blood perfusion, these effects have never been mapped with high-resolution 3-D imaging. We aimed to longitudinally and volumetrically evaluate the effects of microbubbles and nanodroplets on tumor vessel perfusion following HIFU treatment. Rats bearing flank fibrosarcoma tumors were injected with 1.5 × 109 microbubbles (n = 3), nanodroplets (n = 3), or control/no-injection (n = 3) during targeted HIFU (125W/cm2, 1 MHz, 2 MPa, 10% duty cycle, 1 Hz PRF, 3 min). This HIFU power is ~99% less than clinical norms. Tumor perfusion was assessed by contrast enhanced 3-D acoustic angiography before, immediately following, and 72 h after HIFU application. No significant changes in tumor perfusion were observed when HIFU was applied with nanodroplet or control injections. However, HIFU in the presence of microbubbles resulted in a 66.2±15.2% (p < 0.05) reduction in perfused tumor volume. These results suggest that HIFU, when combined with microbubbles, can dramatically remodel tumor vasculature networks even at the low pressure used in this study. This could potentially enhance the safety of HIFU therapy.

High‐Intensity Focused Ultrasound‐Induced Thermal Effect for Solid Polymer Materials

In this study, high‐intensity focused ultrasound (HIFU)‐induced thermal effects for solid polymer materials are investigated systematically. Infrared camera imaging is used to monitor temperature changes. The effects of polymer structure, HIFU power, and sample thickness on the thermal effect are studied. The results show that the HIFU‐induced heating effect is very quickly, and can be controlled spatially and temporally. More importantly, it is obviously different for different polymers. The main reason is attributed to the various inner friction behaviors of macromolecular chains. This fundamental study is helpful to understand the interaction mechanism between HIFU and polymer, when HIFU is used as a trigger for drug release, shape memory, etc. image

Infrared and hydrophone system for eastimating the output power of high intensity focused ultrasound transducer

Output power of high intensity focused ultrasound (HIFU) transducer is not only important for the safety and efficiency of clinical treatment, but also for therapy planning in medical applications. In the current paper, a method was proposed to estimate output power of HIFU using a hydrophone and infrared system. The proposed method is independent of the thermal and acoustic parameters of the acoustic absorber and the type of transducer that has been measured. This method consisted of five steps. The amplitude absorption coefficient of the medium was measured through the first two steps. Through the second and third steps, we estimated the ratio of the heat capacity per unit volume to the ultrasonic amplitude absorption coefficient of the absorber. In fourth step, the temperature change at the absorber/air was captured by an IR camera, and the temperature change rate (TCR) was used to estimate the intensity based on the parameters measured by the first three steps. In last step, the sound power of HIFU transducer at high driving voltage can be obtained following the relationship between the sound intensity and sound power. The method was proposed and simulated in three 2-D 1.36 MHz-phased arrays and two kinds of absorbers. In last step, the sound power of HIFU transducer at high driving voltage can be obtained following the relationship between the sound intensity and sound power.

A New Theranostic System Based on Gold Nanocages and Phase-Change Materials with Unique Features for Photoacoustic Imaging and Controlled Release

This communication reports a new theranostic system with a combination of capabilities to both enhance the contrast of photoacoustic (PA) imaging and control the release of a chemical or biological effector by high-intensity focused ultrasound (HIFU). The fabrication of this system simply involves filling the hollow interiors of gold nanocages with a phase-change material (PCM) such as 1-tetradecanol that has a melting point of 38-39 °C. The PCM can be premixed and thus loaded with a dye, as well as other chemical or biological effectors. When exposed to direct heating or HIFU, the PCM will melt and escape from the interiors of nanocages through small pores on the surface, concurrently releasing the encapsulated molecules into the surrounding medium. We can control the release profile by varying the power of HIFU, the duration of exposure to HIFU, or both.

Gold nanocages covered with thermally-responsive polymers for controlled release by high-intensity focused ultrasound.

This paper describes the use of Au nanocages covered with smart, thermally-responsive polymers for controlled release with high-intensity focused ultrasound (HIFU). HIFU is a highly precise medical procedure that uses focused ultrasound to heat and destroy pathogenic tissue rapidly and locally in a non-invasive or minimally invasive manner. The released dosage could be remotely controlled by manipulating the power of HIFU and/or the duration of exposure. We demonstrated localized release within the focal volume of HIFU by using gelatin phantom samples containing dye-loaded Au nanocages. By placing chicken breast tissues on top of the phantoms, we further demonstrated the feasibility of this system for controlled release at depths up to 30 mm. Because it can penetrate more deeply into soft tissues than near-infrared light, HIFU is a potentially more effective external stimulus for rapid, on-demand drug release.

Dynamic Changes of Integrated Backscatter, Attenuation Coefficient and Bubble Activities During High-Intensity Focused Ultrasound (HIFU) Treatment

This paper simultaneously investigated the transient characteristics of integrated backscatter (IBS), attenuation coefficient and bubble activities as time traces before, during and after HIFU treatment, with different HIFU parameters (acoustic power and duty cycle) in both transparent tissue-mimicking phantoms and freshly excised bovine livers. These dynamic changes of acoustic parameters and bubble activities were correlated with the visualization of lesion development selected from photos, conventional B-mode ultrasound images and differential IBS images over the whole procedure of HIFU treatment. Two-dimensional radiofrequency (RF) data were acquired by a modified diagnostic ultrasound scanner to estimate the changes of mean IBS and attenuation coefficient averaged in the lesion region, and to construct the differential IBS images and B-mode ultrasound images simultaneously. Bubble activities over the whole procedure of HIFU treatment were investigated by the passive cavitation detection (PCD) method and the changes in subharmonic and broadband noise were correlated with the transient characteristics of IBS and attenuation coefficient. When HIFU was switched on, IBS and attenuation coefficient increased with the appearance of bubble clouds in the B-mode and differential IBS image. At the same time, the level of subharmonic and broadband noise rose abruptly. Then, there was an initial decrease in the attenuation coefficient, followed by an increase when at lower HIFU power. As the lesion appeared, IBS and attenuation coefficient both increased rapidly to a value twice that of normal. Then the changes in IBS and attenuation coefficient showed more complex patterns, but still showed a slower trend of increases with lesion development. Violent bubble activities were visible in the gel and were evident as strongly echogenic regions in the differential IBS images and B-mode images simultaneously. This was detected by a dramatic high level of subharmonic and broadband noise at the same time. These bubble activities caused fluctuations in IBS and attenuation coefficient during HIFU treatment. After HIFU, IBS and attenuation coefficient decreased gradually accompanied by the fadeout of bright hyperechoic spot in the B-mode and differential IBS image, but were still higher than normal when they were stable. The increases of IBS and attenuation coefficient were greater when using higher acoustic power or a higher duty cycle of the therapeutic emission. These experiments indicated that the bubble activities had the dominant effects on the transient characteristics of IBS and attenuation. This should be taken into consideration when using the dynamic acoustic-property changes for the potentially real-time monitoring imaging of HIFU treatment. (E-mail: mxwan@mail.xjtu.edu.cn)

Millisecond initiation of boiling by high-intensity focused ultrasound in tissue-mimicking phantoms

Nonlinear propagation effects leading to shock formation at the focus of high-intensity focused ultrasound (HIFU) treatments can accelerate heating and cause rapid boiling in tissue. Boiling can be utilized for targeting the treatment with B-mode ultrasound and should be taken into account when planning the treatment, because bubbles reflect ultrasound and thereby displace and distort the lesion shape. In these experiments, an HIFU transducer of 2-MHz frequency, 4-cm aperture, and 4.5-cm focal length was used to investigate heating effects from shock formation in tissue-mimicking phantoms. The time required to attain 100&amp;lt;th&amp;gt;°C at the focus was calculated with weak shock theory from the peak amplitudes calculated with a KZK-type model, and time to boiling was measured by high-speed video and a 20–MHz passive cavitation detector (PCD) for different values of phantom absorption (both lower than tissue absorption) and HIFU power (100–200 W). Boiling was observed in 3 ms at the highest power level used by the observation of visible bubbles and by a significant change in the PCD time signal and spectrum. [Work supported by NIH DK43881, NSBRI SMS00402, and RFBR.]

Spatial distributions of acoustic parameters in high-intensity focused ultrasound fields

Different peak and average acoustic parameters determine the efficiency of different physical mechanisms of high-intensity focused ultrasound (HIFU) interaction with biological tissue. Spatial distributions of these parameters are therefore important for transducer calibration and extrapolation of measurements in water to application in tissue. In the case of linear focusing, all parameters of the acoustic field can be obtained from the spatial distribution of the wave amplitude. However, in nonlinear focused beams, each parameter has its own characteristic spatial structure, which changes with the increase of the HIFU power level. This work compares the focal size and location calculated for the peak positive and peak negative pressure, mean intensity, and effective acoustic energy absorption in water and in tissue. Numerical solutions, obtained with the KZK-type model, are analyzed for various regimes of linear, quasilinear, and strongly nonlinear propagation which includes formation of shocks. The results of simulations are validated by comparison with measurements performed with a fiber-optic probe hydrophone in water and in a tissue-mimicking phantom. The peak positive pressure and effective absorption are finely focused, whereas the negative pressure, responsible for cavitation, is broad and displaced towards the transducer. [Work supported by NSBRI SMS00402, RFBR, and NIH DK43881.]

Focal Gene Induction in the Liver of Rats by a Heat-Inducible Promoter Using Focused Ultrasound Hyperthermia

We sought to examine high-intensity focused ultrasound (HIFU)-induced hyperthermia in the liver of a rat model to focally induce green-fluorescent protein (GFP). A total of 25 Copenhagen rats were included in this study. Rats were divided into groups treated with an adenovirus coding for green fluorescent protein (GFP) under the control of a hsp70B promoter and a CMV promoter. Ad-CMV-GFP-treated rats served as positive control. Untreated controls only subjected to MRI +/- HIFU-treatment served to find out optimal power of HIFU in the target area of the liver. Temperature was noninvasively monitored by temperature sensitive magnetic resonance imaging (MRI). Rats treated with Ad-hsp70B-GFP demonstrated localized gene induction within the liver parenchyma, in good correlation with MRI and histology. Applying an acoustic power of 1.92 W a relatively uniform focal temperature up to 42 +/- 5 degrees C within the liver parenchyma could be documented. 3 x 10(9) plaque-forming units proved to account for a very homogeneous liver infection. Number of fluorescent cells in the region of hyperthermia was similar to the control group treated with Ad-CMV-GFP. Using the introduced parameters spatially controlled gene induction within a parenchymal organ such as the liver in rats using HIFU under control of MRI is feasible.