High Intensity Focused Ultrasound Beam Research Articles

Algebraic reconstruction technique considering curved ray for sound-speed tomography with ring-array transducer

Our objective is to develop an ultrasound treatment and diagnosis integrated system for breast cancer. Ultrasound computed tomography (UCT) in imaging and high intensity focused ultrasound (HIFU) in therapy was integrated to achieve ideal treatment system. Profiles of sound speed and attenuation obtained by UCT has informative parameters to correct deformation of HIFU beam. We try to develop an imaging system using ring-array transducer with 1024-elements, multiplexer connecting 1024 to 256 and Verasonics programmable imaging system with 256 channels. First, an iterative Simultaneous Algebraic Reconstruction Technique (SART) reconstruction methods with an assumption of straight path was employed. SART was applied to projection data calculated by a FEM simulator treating actual curved ray caused by tissue inhomogeneity. In these results, estimated error in sound speed difference was 53%. Then we introduced Linear Travel-time Interpolation (LTI) to SART to implement effects of curved ray. LTI is a ray tracing method based on Fermat’s Principle. We evaluated the LTI and SART integrated method for sound-speed tomography. Travel-time for reconstruction was achieved from simulation based on finite difference method. The reconstruction image was highly corresponded with original image. Reconstructed image from experimental projection data will be reported in the presentation.

Effects of MRTI sampling characteristics on estimation of HIFU SAR and tissue thermal diffusivity

While the non-invasive and three-dimensional nature of magnetic-resonance temperature imaging (MRTI) makes it a valuable tool for high-intensity focused ultrasound (HIFU) treatments, random and systematic errors in MRTI measurements may propagate into temperature-based parameter estimates used for pretreatment planning. This study assesses the MRTI effects of zero-mean Gaussian noise (SD = 0.0–2.0 °C), temporal sampling (tacq = 1.0–8.0 s), and spatial averaging (Res = 0.5–2.0 mm isotropic) on HIFU temperature measurements and temperature-based estimates of the amplitude and full width half maximum (FWHM) of the HIFU specific absorption rate and of tissue thermal diffusivity. The ultrasound beam used in simulations and ex vivo pork loin experiments has lateral and axial FWHM dimensions of 1.4 mm and 7.9 mm respectively. For spatial averaging simulations, beams with lateral FWHM varying from 1.2–2.2 mm are also assessed. Under noisy conditions, parameter estimates are improved by fitting to data from larger voxel regions. Varying the temporal sampling results in minimal changes in measured temperatures (<2% change) and parameter estimates (<5% change). For the HIFU beams studied, a spatial resolution of 1 × 1 × 3 mm3 or smaller is required to keep errors in temperature and all estimated parameters less than 10%. By quantifying the errors associated with these sampling characteristics, this work provides researchers with appropriate MRTI conditions for obtaining estimates of parameters essential to pretreatment modeling of HIFU thermal therapies.

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 f1.2. 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.

Real-time temperature estimation and monitoring of HIFU ablation through a combined modeling and passive acoustic mapping approach**Portions presented at the 13th International Symposium on Therapeutic Ultrasound, Heidelberg, Germany (2012).

Passive acoustic mapping (PAM) has been recently demonstrated as a method of monitoring focused ultrasound therapy by reconstructing the emissions created by inertially cavitating bubbles (Jensen et al 2012 Radiology 262 252–61). The published method sums energy emitted by cavitation from the focal region within the tissue and uses a threshold to determine when sufficient energy has been delivered for ablation. The present work builds on this approach to provide a high-intensity focused ultrasound (HIFU) treatment monitoring software that displays both real-time temperature maps and a prediction of the ablated tissue region. This is achieved by determining heat deposition from two sources: (i) acoustic absorption of the primary HIFU beam which is calculated via a nonlinear model, and (ii) absorption of energy from bubble acoustic emissions which is estimated from measurements. The two sources of heat are used as inputs to the bioheat equation that gives an estimate of the temperature of the tissue as well as estimates of tissue ablation. The method has been applied to ex vivo ox liver samples and the estimated temperature is compared to the measured temperature and shows good agreement, capturing the effect of cavitation-enhanced heating on temperature evolution. In conclusion, it is demonstrated that by using PAM and predictions of heating it is possible to produce an evolving estimate of cell death during exposure in order to guide treatment for monitoring ablative HIFU therapy.

HIFU Beam Imaging Based on Scattering Signals from Focal Area

High-Intensity Focused Ultrasound (HIFU) is one of minimally invasive surgical procedures. However there are refractions and reflections which cause the actual focal point deviates from the geometrical focal point of transducer. To control the focal position of HIFU, visualizing inside of the body and HIFU beam before treatment is essentially required. We developed a HIFU beam imaging method for our HIFU treatment system consisting with robotic system, HIFU transducer and electronic circuit. By using receiving beam scan with a linear imaging array probe synchronizing with a transmission of pulse from the HIFU transducer, HIFU beam and surrounding tissues were imaged by an ultrasound imaging system. This result shows that the proposed method was useful to assist the planning of HIFU therapy.

High-intensity focused ultrasound plus concomitant radiotherapy: a new weapon in oncology?

The potential impact of high-intensity focused ultrasound (HIFU) to general medicine and oncology seems very high. However, while in the research area, the development of this technique is very rapid and unchallenged. The direct application of HIFU to human tumour therapy is hampered by various technical difficulties, which may confine its role to a marginal device in the surgery armamentarium. To deploy the full potential of focused ultrasound in oncology, it seems necessary to review the basic relationship between HIFU and external beam radiotherapy. This is the aim of the present work.

High-Intensity Focused Ultrasound (HIFU) for Dissolution of Clots in a Rabbit Model of Embolic Stroke

It is estimated that only 2–6% of patients receive thrombolytic therapy for acute ischemic stroke suggesting that alternative therapies are necessary. In this study, we investigate the potential for high intensity focused ultrasound (HIFU) to initiate thrombolysis in an embolic model of stroke. Iron-loaded blood clots were injected into the middle cerebral artery (MCA) of New Zealand White rabbits, through the internal carotid artery and blockages were confirmed by angiography. MRI was used to localize the iron-loaded clot and target the HIFU beam for treatment. HIFU pulses (1.5 MHz, 1 ms bursts, 1 Hz pulse repetition frequency, 20 s duration) were applied to initiate thrombolysis. Repeat angiograms and histology were used to assess reperfusion and vessel damage. Using 275 W of acoustic power, there was no evidence of reperfusion in post-treatment angiograms of 3 rabbits tested. In a separate group of animals, 415 W of acoustic power was applied and reperfusion was observed in 2 of the 4 (50%) animals treated. In the last group of animals, acoustic power was further increased to 550 W, which led to the reperfusion in 5 of 7 (∼70%) animals tested. Histological analysis confirmed thatthe sonicated vessels remained intact after HIFU treatment. Hemorrhage was detected outside of the sonication site, likely due to the proximity of the target vessel with the base of the rabbit skull. These results demonstrate the feasibility of using HIFU, as a stand-alone method, to cause effective thrombolysis without immediate damage to the targeted vessels. HIFU, combined with imaging modalities used to identify and assess stroke patients, could dramatically reduce the time to achieve flow restoration in patients thereby significantly increasing the number of patients which benefit from thrombolysis treatments.

Photoacoustic-guided ultrasound therapy with a dual-mode ultrasound array

Photoacoustics has recently been proposed as a potential method to guide and/or monitor therapy based on high-intensity focused ultrasound (HIFU). We experimentally demonstrate the creation of a HIFU lesion at the location of an optical absorber, by use of photoacoustic signals emitted by the absorber detected on a dual mode transducer array. To do so, a dedicated ultrasound array intended to both detect photoacoustic waves and emit HIFU with the same elements was used. Such a dual-mode array provides automatically coregistered reference frames for photoacoustic detection and HIFU emission, a highly desired feature for methods involving guidance or monitoring of HIFU by use of photoacoustics. The prototype is first characterized in terms of both photoacoustic and HIFU performances. The probe is then used to perform an idealized scenario of photoacoustic-guided therapy, where photoacoustic signals generated by an absorbing thread embedded in a piece of chicken breast are used to automatically refocus a HIFU beam with a time-reversal mirror and necrose the tissue at the location of the absorber.

Ultrasonography-based 2D motion-compensated HIFU sonication integrated with reference-free MR temperature monitoring: a feasibility study ex vivo

Magnetic resonance imaging (MRI) and ultrasonography have been used simultaneously in this ex vivo study for the image-guidance of high intensity focused ultrasound (HIFU) treatment in moving tissue. A ventilator-driven balloon produced periodic and non-rigid (i.e. breathing-like) motion patterns in phantoms. MR-compatible ultrasound (US) imaging enabled near real-time 2D motion tracking based on optical flow detection, while near-harmonic reference-free proton resonance frequency shift (PRFS) MR thermometry (MRT) was used to monitor the thermal buildup on line. Reference-free MRT was applied to gradient-echo echo-planar imaging phase maps acquired at the frame rate of 250 to 300 ms/slice with voxel size 1.25×1.25×5 mm3. The MR-US simultaneous imaging was completely free of mutual interferences while minor RF interferences from the HIFU device were detected in the far field of the US images. The effective duty-cycle of the HIFU sonication was close to 100 % and no off-interval was required to temporally decouple it from the ultrasonography. The motion compensation of the HIFU sonication was achieved with an 8 Hz frame rate and sub-millimeter spatial accuracy, both for single-focus mode and for an iterated multi-foci line scan. Near harmonic reference-less PRFS MRT delivered motion-robust thermal maps perpendicular or parallel to the HIFU beam (0.7 °C precision, 0.5 °C absolute accuracy). Out-of-plane motion compensation was not addressed in this study.

Microbubble-enhanced high intensity focused ultrasound therapy: effect of exposure parameters on thermal lesion volume and temperature

Microbubble agents have been shown to increase therapeutic effect of HIFU (high intensity focused ultrasound). Here, the effects of treatment parameters on lesion volume and temperature are investigated. Ex vivo tissue was treated with a 2 MHz HIFU beam in absence and presence of the Artenga™ microbubbles at varying HIFU focal intensities (649-2316 W/cm2), microbubble concentrations, and exposure durations (3-10 s). The temperature was measured at 1 mm from focus using a K-type thermocouple. Thermal lesion volume was measured based on an ellipsoid model. Microbubbles increased the lesion volume and peak temperature achieved with HIFU. At the intensity of 2316 W/cm2, the lesion volume increased by 2-folds, and the peak temperature increased by 16° C with microbubbles. This effect depended on microbubble concentration, ultrasound intensity and exposure duration. Lower intensities and shorter time durations were required at higher microbubble concentrations to ablate the tissue. It was concluded that the efficacy of the HIFU therapy in combination with microbubbles can be controlled through ultrasound/microbubble exposure parameters

Optimal transcostal high-intensity focused ultrasound with combined real-time 3D movement tracking and correction

Recent studies have demonstrated the feasibility of transcostal high intensity focused ultrasound (HIFU) treatment in liver. However, two factors limit thermal necrosis of the liver through the ribs: the energy deposition at focus is decreased by the respiratory movement of the liver and the energy deposition on the skin is increased by the presence of highly absorbing bone structures. Ex vivo ablations were conducted to validate the feasibility of a transcostal real-time 3D movement tracking and correction mode. Experiments were conducted through a chest phantom made of three human ribs immersed in water and were placed in front of a 300 element array working at 1 MHz. A binarized apodization law introduced recently in order to spare the rib cage during treatment has been extended here with real-time electronic steering of the beam. Thermal simulations have been conducted to determine the steering limits. In vivo 3D-movement detection was performed on pigs using an ultrasonic sequence. The maximum error on the transcostal motion detection was measured to be 0.09 ± 0.097 mm on the anterior–posterior axis. Finally, a complete sequence was developed combining real-time 3D transcostal movement correction and spiral trajectory of the HIFU beam, allowing the system to treat larger areas with optimized efficiency. Lesions as large as 1 cm in diameter have been produced at focus in excised liver, whereas no necroses could be obtained with the same emitted power without correcting the movement of the tissue sample.

Effects of gas pockets on high-intensity focused ultrasound field

The paper describes experimental and numerical studies of the effects of gas pockets on a high-intensity focused ultrasound (HIFU) field. Air bubbles ranging from 0.8 to 2.4 mm in radius were produced in transparent polyacrylamide tissue-mimicking gels. A single-element 3.5-MHz HIFU transducer was used to sonicate the gel phantoms. The changes in the HIFU beam pattern for air bubbles at different positions were visualized by the Schlieren method. Quantitative measurements of pressure at the HIFU focus by a calibrated needle hydrophone showed considerable reduction in the focal pressure with the presence of an air pocket. The presence of a single 1.2-mm-radius air bubble, at a 5 mm axial pre-focal position, reduced the focal intensity by 50% and increased the lateral focal dimension by 50%. For air bubbles at pre-focal position close to the focus, lesion formation was observed not at the theoretical focus, but in front of the air bubble and the air bubble became a barrier for the post-focal ultrasound propagation. The effects of reflection were simulated numerically and were compared with the experiments. The results can be used as guidelines for evaluation of potential safety concerns produced by trapped gas-pockets in various HIFU therapies.

Evaluation of temperature rise in a tissue mimicking material during HIFU exposure

In pre-clinical testing it is essential to characterize clinical high intensity focused ultrasound (HIFU) devices using tissue-mimicking materials (TMMs) with well known characteristics, including temperature rise and cavitation properties. The purpose of this study was to monitor cavitation behavior and correlate its effect with temperature rise in a HIFU TMM containing an embedded thermocouple. A 75-μm fine wire thermocouple was embedded in a hydrogel-based TMM previously developed for HIFU. HIFU at 1.1 and 3.3 MHz was focused at the thermocouple junction. Focal pressures from 1-11 MPa were applied and the temperature profiles were recorded. Three hydrophones were used to monitor cavitation activity during sonication. A hydrophone confocal with the HIFU transducer and a cylindrical hydrophone lateral to the HIFU beam were used as passive cavitation detectors for spectral analysis of signals, and a needle hydrophone placed beyond the HIFU focus was used to record changes in the pressure amplitude due to blockage by bubbles at or near the focus. B-mode imaging scans were employed to visualize bubble presence during sonication. In a separate measurement, schlieren imaging was used to monitor the change in field distribution behind the TMM. All hydrophone methods correlated well with cavitation in the TMM.

A Preclinical In Vivo Investigation of High-Intensity Focused Ultrasound Combined with Radiotherapy

This study aims to perform an in vivo investigation evaluating the injury to the pancreas and adjacent tissue of swine resulting with high-intensity focused ultrasound (HIFU) combined with radiotherapy (RT). The protocol was approved by the animal ethics committee at the Peking University First Hospital. A total of 12 domestic swine were divided into four groups: control, HIFU only, RT only and HIFU + RT. The injury to the pancreas, adjacent tissue and tissue within the acoustic path of the HIFU beam was assessed based on gross and histologic findings. For the targeted region of the pancreas, the score of the combined group was higher than that of the HIFU group and there was significant difference. For the acoustic path tissue, there was no significant difference except between the control group and the other groups. HIFU combined with RT increased the injury to the targeted pancreas, without increased injury to tissue outside of the targeted region. (E-mail: xsgao777@hotmail.com)

Beam localization in HIFU temperature measurements using thermocouples, with application to cooling by large blood vessels

Experimental studies of thermal effects in high-intensity focused ultrasound (HIFU) procedures are often performed with the aid of fine wire thermocouples positioned within tissue phantoms. Thermocouple measurements are subject to several types of error which must be accounted for before reliable inferences can be made on the basis of the measurements. Thermocouple artifact due to viscous heating is one source of error. A second is the uncertainty regarding the position of the beam relative to the target location or the thermocouple junction, due to the error in positioning the beam at the junction. This paper presents a method for determining the location of the beam relative to a fixed pair of thermocouples. The localization technique reduces the uncertainty introduced by positioning errors associated with very narrow HIFU beams. The technique is presented in the context of an investigation into the effect of blood flow through large vessels on the efficacy of HIFU procedures targeted near the vessel. Application of the beam localization method allowed conclusions regarding the effects of blood flow to be drawn from previously inconclusive (because of localization uncertainties) data. Comparison of the position-adjusted transient temperature profiles for flow rates of 0 and 400 ml/min showed that blood flow can reduce temperature elevations by more than 10%, when the HIFU focus is within a 2 mm distance from the vessel wall. At acoustic power levels of 17.3 and 24.8 W there is a 20- to 70-fold decrease in thermal dose due to the convective cooling effect of blood flow, implying a shrinkage in lesion size. The beam-localization technique also revealed the level of thermocouple artifact as a function of sonication time, providing investigators with an indication of the quality of thermocouple data for a given exposure time. The maximum artifact was found to be double the measured temperature rise, during initial few seconds of sonication.

Effects of ribs in high intensity focused ultrasound beam path on formation of coagulated necrosis in cattle liver in vitro

Objective To investigate the effects of ribs in high intensity focused ultrasound (HIFU)beam path on formation of coagulative necrosis in cattle liver in vitro in the same acoustic power. Methods The HIFU ablation was carried out in the manner of a single dot in the liver in vitro. The liver was ablated by HIFU in free field,then the ribs were placed between the focal plane and transducer,directing the beam axis through the intercostals space, lied at the rib edge and on the centre of middle rib. For each of these axial arrangements,the plane of the front surface of ribs was placed 3 cm,6 cm or 9 cm in front of the focus. After HIFU exposure,the tissue necrosis rate(TNR),the maximum length,width,depth and position of the coagulated necrosis in the liver were measured. Results ①The TNR was 100% in the free field. When the ribs were placed 3 cm in front of the focal plane,directing the beam axis through the intercostals space, the TNR was 100%. When directing the beam axis lied at the rib edge and on the centre of middle rib,the TNR decreased sharply. When the ribs were placed 6cm and 9cm in front of the focal plane, the TNR was more than 50%. ②When the ribs were placed in HIFU beam path, the volume of necrosis decreased compared with those in free field. The relationship between the ribs and beam axis, the location of ribs placed away from the focal plane different,the volume,length,width and position of the coagulated necrosis different. ③ When the ribs were close to the focal plane,unacceptable damage could been observed on the surface of ribs.When the ribs were far away from the focal plane, the ribs were safe. Conclusions The volume of necrosis decrease when the ribs are placed in HIFU beam path. The relative location of ribs and HIFU beam axis, the location of ribs away from the focal plane are relative with the volume of the coagulated necrosis. When directing the beam axis through the intercostals space, the volume of necrosis is large, and the shape of coagulated necrosis is regulated. When the ribs are closed with the focal plane,ribs are damaged probably. Key words: Ultrasound,high intensity focused; Ribs; Coagulated necrosis; Rib-like barrier

A method for MRI guidance of intercostal high intensity focused ultrasound ablation in the liver

High intensity focused ultrasound (HIFU) is a promising method for the noninvasive treatment of liver tumors. However, the presence of ribs in the HIFU beam path remains problematic since it may lead to adverse effects (skin burns) by absorption and reflection of the incident beam at or near the bone surface. This article presents a method based on magnetic resonance (MR) imaging for identification of the ribs in the HIFU beam, and for selection of the transducer elements to deactivate. The ribs are visualized on anatomical images acquired prior to heating and manually segmented. The resulting regions of interest surrounding the ribs are projected onto the transducer surface by ray tracing from the focal point. The transducer elements in the "shadow" of the ribs are then deactivated. The method was validated ex vivo and in vivo in pig liver during breathing under multislice real-time MR thermometry, using the proton resonance frequency shift method. Ex vivo and in vivo temperature data showed that the temperature increase near the ribs was substantial when HIFU sonications were performed with all elements active, whereas the temperature was reduced with deactivation of the transducer elements located in front of the ribs. The temperature at the focal point was similar with and without deactivation of the transducer elements, indicative of no loss of heat efficiency with the proposed technique. This method is simple, rapid, and reliable, and enables intercostal HIFU ablation while sparing ribs and their surrounding tissues.

Adaptive HIFU noise cancellation for simultaneous therapy and imaging using an integrated HIFU/imaging transducer

It was previously demonstrated that it is feasible to simultaneously perform ultrasound therapy and imaging of a coagulated lesion during treatment with an integrated transducer that is capable of high intensity focused ultrasound (HIFU) and B-mode ultrasound imaging. It was found that coded excitation and fixed notch filtering upon reception could significantly reduce interference caused by the therapeutic transducer. During HIFU sonication, the imaging signal generated with coded excitation and fixed notch filtering had a range side-lobe level of less than −40 dB, while traditional short-pulse excitation and fixed notch filtering produced a range side-lobe level of −20 dB. The shortcoming is, however, that relatively complicated electronics may be needed to utilize coded excitation in an array imaging system. It is for this reason that in this paper an adaptive noise canceling technique is proposed to improve image quality by minimizing not only the therapeutic interference, but also the remnant side-lobe ‘ripples’ when using the traditional short-pulse excitation. The performance of this technique was verified through simulation and experiments using a prototype integrated HIFU/imaging transducer. Although it is known that the remnant ripples are related to the notch attenuation value of the fixed notch filter, in reality, it is difficult to find the optimal notch attenuation value due to the change in targets or the media resulted from motion or different acoustic properties even during one sonication pulse. In contrast, the proposed adaptive noise canceling technique is capable of optimally minimizing both the therapeutic interference and residual ripples without such constraints. The prototype integrated HIFU/imaging transducer is composed of three rectangular elements. The 6 MHz center element is used for imaging and the outer two identical 4 MHz elements work together to transmit the HIFU beam. Two HIFU elements of 14.4 mm × 20.0 mm dimensions could increase the temperature of the soft biological tissue from 55 °C to 71 °C within 60 s. Two types of experiments for simultaneous therapy and imaging were conducted to acquire a single scan-line and B-mode image with an aluminum plate and a slice of porcine muscle, respectively. The B-mode image was obtained using the single element imaging system during HIFU beam transmission. The experimental results proved that the combination of the traditional short-pulse excitation and the adaptive noise canceling method could significantly reduce therapeutic interference and remnant ripples and thus may be a better way to implement real-time simultaneous therapy and imaging.

Comparison of the Khokhlov–Zabolotskaya–Kuznetsov equation and Fourier-continuation for modeling high-intensity focused ultrasound beams.

High-intensity focused ultrasound (HIFU) employs acoustic amplitudes that are high enough that nonlinear propagation effects are important in the evolution of the sound field. A common model for HIFU beams is the Khokhlov–Zabolotskaya–Kuznetsov (KZK) equation which accounts for nonlinearity and absorption of sound beams. The KZK equation models diffraction using the parabolic or paraxial approximation. For many HIFU sources the source aperture is similar to the focal length and the paraxial approximation may not be appropriate. Here we compare results obtained using the “Texas code” a time-domain numerical solution to the KZK equation to a new method of solving nonlinear differential equations: the Fourier-continuation (FC) method. Here the FC method solves the underlying fluid dynamics equations and does not invoke the paraxial approximation. Results were obtained for a 1.1-MHz focused HIFU source. The medium parameters were taken to either be hyperviscous water or to match human liver. For a low focusing gain transducer (focal length 50λ and radius 10λ) the KZK and FC models showed excellent agreement through the focal region. As the source radius was increased, discrepancies started to appear and for a radius of 30λ, the KZK model did not capture diffraction of the HIFU source accurately. [Work supported by NSF 0835795.]

Thermal effects generated by high-intensity focused ultrasound beams at normal incidence to a bone surface

Experiments and computations were performed to study factors affecting thermal safety when high-intensity focused ultrasound (HIFU) beams are normally incident (i.e., beam axis normal to the interface) upon a bone/soft-tissue interface. In particular, the temperature rise and thermal dose were determined as a function of separation between the beam focus and the interface. Under conditions representative of clinical HIFU procedures, it was found that the thermal dose at the bone surface can exceed the threshold for necrosis even when the beam focus is more than 4 cm from the bone. Experiments showed that reflection of the HIFU beam from the bone back into the transducer introduced temperature fluctuations of as much as +/-15% and may be an important consideration for safety analyses at sufficiently high acoustic power. The applicability of linear propagation models in predicting thermal dose near the interface was also addressed. Linear models, while underpredicting thermal dose at the focus, provided a conservative (slight overprediction) estimate of thermal dose at the bone surface. Finally, temperature rise due to absorption of shear waves generated by the HIFU beam in the bone was computed. Modeling shear-wave propagation in the thermal analysis showed that the predicted temperature rise off axis was as much as 30% higher when absorption of shear waves is included, indicating that enhanced heating due to shear-wave absorption is potentially important, even for normally incident HIFU beams.