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Acoustic attenuation in the propagation path of focused ultrasound ablation surgery determines the energy loss toward the focal region and is critical to the consequent treatment outcomes. In situ non-invasive, reliable, and accurate measurement is challenging for multi-layered heterogeneous tissues within the focusing angle. A novel measurement approach is proposed and its performance is evaluated using ex vivo porcine tenderloin and bovine heart. A big boiling bubble (i.e., larger than a few millimeters in size) was produced at the focus as a strong reflector inside the tissue, and the echo amplitudes were used to determine the acoustic attenuation. Two models, acoustic ray and energy loss, were developed to derive the equivalent acoustic attenuation coefficient for a focused beam. The measured acoustic attenuation coefficients of ex vivo porcine tenderloin and bovine heart at 0.97 MHz and a thickness of 3 cm are 0.159 ± 0.002 and 0.250 ± 0.005 Np/cm, respectively, which are all within the scope of measured values in the literature. In addition, the echo amplitude is sensitive to the conditions of the propagation path, and the inverse acoustic attenuation coefficient of the silicone gel pad placed in front of the tissue sample was 0.807 ± 0.002 Np/cm, which is comparable to the measurement using the insertion substitution method, 0.766 ± 0.003 Np/cm. Our proposed approach could determine the tissue acoustic attenuation for focused ultrasound ablation surgery reliably and accurately in situ. The easy operating protocol may allow clinical translation and adoption for improved safety and efficacy. [ABSTRACT FROM AUTHOR]

Background: High‐intensity focused ultrasound (HIFU) has been in clinical use for a variety of solid tumors and cancers. Accurate and reliable calibration is in a great need for clinical applications. An extracorporeal clinical HIFU system applied for the investigational device exemption (IDE) to the Food and Drug Administration (FDA) so that evaluation of its characteristics, performance, and safety was required. Methods: The acoustic pressure and power output was characterized by a fiber optic probe and a radiation force balance, respectively, with the electrical power up to 2000 W. An in situ acoustic energy was established as the clinical protocol at the electrical power up to 500 W. Temperature elevation inside the tissue sample was measured by a thermocouple array. Generated lesion volume at different in situ acoustic energies and pathological examination of the lesions was evaluated ex vivo. Results: Acoustic pressure mapping showed the insignificant presence of side/grating lobes and pre‐ or post‐focal peaks (≤−12 dB). Although distorted acoustic pressure waveform was found in the free field, the nonlinearity was reduced significantly after the beam propagating through tissue samples (i.e., the second harmonic of −11.8 dB at 500 W). Temperature elevation was <10°C at a distance of 10 mm away from a 20‐mm target, which suggests the well‐controlled HIFU energy deposition and no damage to the surrounding tissue. An acoustic energy in the range of 750–1250 J resulted in discrete lesions with an interval space of 5 mm between the treatment spots. Histology confirmed that the lesions represented a region of permanently damaged cells by heat fixation, without causing cell lysis by either cavitation or boiling. Conclusions: Our characterization and ex vivo evaluation protocol met the IDE requirement. The in‐situ acoustic energy model will be used in clinical trials to deliver almost consistent energy to the various targets. [ABSTRACT FROM AUTHOR]

High-intensity focused ultrasound (HIFU) has been used successfully in clinics for the treatment of a variety of cancerous and benign tumors. Characterization of the focused acoustic field is of importance in the planning of the ablation procedure and further development of HIFU technology. Quantitative estimation of acoustic intensity is feasible using the infrared (IR) thermography on an absorber. However, the current approach is limited to low power output. In this study, a theoretical model was established to describe the acoustic field and absorbed energy in the absorber with the presence of harmonics in the HIFU pressure waveform at the focus and then to calculate the temperature elevations during the HIFU heating, from which the acoustic intensities could be derived. The absolute difference between the derived and incident acoustic intensities in a 2-mm absorber at the varied acoustic power output (up to 80 W) and attenuation of the absorber (up to 346 Np/m/MHz) is <6%. In addition, the proposed approach was found to also work well for the absorber with a varied thickness because of the monotonic decrease of the temperature elevation. The effects of pulse duration and duty cycle of pulsed HIFU ablation on the estimation accuracy were also investigated. It is found that the estimation accuracy is good for short pulse duration using the equivalent acoustic intensity. Overall, the proposed approach could estimate the acoustic intensity and harmonic distribution of HIFU at the high power output using IR thermography for a large parametric range of absorber and HIFU output in the numerical investigation. [ABSTRACT FROM AUTHOR]

High-intensity focused ultrasound (HIFU) has emerged as an effective and noninvasive therapeutic modality for cancer and solid tumor. Despite its promising clinical outcomes and the approval of the Food and Drug Administration of many countries, the ablation time of a large target is long, so enhancement of the lesion production is highly desired. In this study, dual-frequency (or amplitude modulation) excitation was evaluated both numerically and experimentally, and its performance was compared with that using single-frequency excitation at the same power output. The nonlinear wave propagation model was used to simulate the acoustic field of HIFU exposure, the Gilmore model was used to determine the induced bubble dynamics, and then absorbed acoustic energy and bubble-enhanced heating were put into the BioHeat equation to calculate the temperature elevation. HIFU-produced lesion in the bovine serum albumin-embedded polyacrylamide was recorded photographically. It is found that dual-frequency excitation (3.16 + 3.20MHz) can increase the lesion area by 35%–65% compared to single-frequency excitation (3.18 MHz) at the same power output. The lesion enhancement increases with the pulse repetition frequency, duty cycle, and modulation depth and decreases with the frequency difference. In summary, dual-frequency excitation can increase the bubble cavitation and the associated heating for HIFU ablation for large lesion production. [ABSTRACT FROM AUTHOR]

Purpose: High‐intensity focused ultrasound (HIFU) is becoming an effective and noninvasive treatment modality for cancer and solid tumors. In order to avoid the cancer relapse and guarantee the success of ablation, there should be no gaps left among all HIFU‐generated lesions. However, there are few imaging approaches available for detecting the HIFU lesion gaps in real time during ablation. Methods: Transient axial shear strain elastograms (ASSEs) were proposed and evaluated both numerically and experimentally to detect the lesion gaps immediately after the cessation of therapeutic HIFU exposure. Acoustic intensity and subsequent acoustic radiation force were first calculated by solving the nonlinear Khokhlov–Zabolotskaya–Kuznetzov (KZK) equation. Motion of being‐ and already‐treated lesions during and after HIFU exposure was simulated using the transient dynamic analysis module of finite element method (FEM). The corresponding B‐mode sonography of tissue‐mimicking phantom with two HIFU lesions inside was simulated by FIELD II, and then axial strain elastograms (ASEs) under static compression and transient ASSEs were reconstructed. An ultrasound imaging probe was integrated with the HIFU transducer and used to obtain radio frequency (RF) echo signals at high frame rate using plane wave imaging (PWI). The resulting strains were mapped using the correlation‐based method and block search strategy. Results: Acoustic radiation force from the therapeutic HIFU burst is sufficiently strong to produce significant displacement. As a result, large and highly localized axial shear strain appears in the gap zone between two HIFU‐generated lesions and then disappears after sufficient HIFU ablation (no gap between them). Such capability of detecting the lesion gap is validated at the varied acoustic radiation force density, gap width, and the size of the lesion. In contrast, conventional ASEs using the static compression cannot distinguish whether a gap exists between lesions. Static ASEs and transient ASSEs reconstructed using both high‐speed photography and sonography in the gel phantom show the same conclusion as that in the simulation. Ex vivo tissue experiments further confirmed that the presence of large axial shear strain in the gap zone. The ratios of axial shear strain in the porcine kidney and liver samples had statistical differences for two HIFU‐generated lesions without and with a gap (P < 0.05). Conclusions: Large axial shear strain induced by the acoustic radiation force from therapeutic HIFU burst only appears between two HIFU‐generated lesions with a gap between them. Transient ASSEs reconstructed immediately after the cession of HIFU exposure can easily, reliably, and sensitively detect the gap between produced lesions, which would provide real‐time feedback to enhance the success of HIFU ablation. [ABSTRACT FROM AUTHOR]

High-intensity focused ultrasound (HIFU) has been emerging as an effective and noninvasive modality in cancer treatment with very promising clinical results. However, a small vessel in the focal region could be ruptured, which is an important concern for the safety of HIFU ablation. In this study, lesion formation in the polyacrylamide gel phantom embedded with different tubing (inner diameters of 0.76 mm and 3 mm) at varied flow speeds (17–339 cm/s) by HIFU ablation was photographically recorded. Produced lesions have decreased length (~30%) but slightly increased width (~6%) in comparison to that without the embedded tubing. Meanwhile, bubble activities during the exposures were measured by passive cavitation detection (PCD) at the varied pulse repetition frequency (PRF, 10–30 Hz) and duty cycle (DC, 10%-20%) of the HIFU bursts. High DC and low flow speed were found to produce stronger bubble cavitation whereas no significant influence of the PRF. In addition, high-speed photography illustrated that the rupture of tubing was produced consistently after the first HIFU burst within 20 ms and then multiple bubbles would penetrate into the intraluminal space of tubing through the rupture site by the acoustic radiation force. Alignment of HIFU focus to the anterior surface, middle, and posterior surface of tubing led to different characteristics of vessel rupture and bubble introduction. In summary, HIFU-induced vessel rupture is possible as shown in this phantom study; produced lesion sizes and shapes are dependent on the focus alignment to the tubing, flow speed, and tubing properties; and bubble cavitation and the formation liquid jet may be one of the major mechanisms of tubing rupture as shown in the high-speed photography. [ABSTRACT FROM AUTHOR]

Purpose: HIFU has been emerging as an effective and safe modality for the treatment of solid tumours and cancers. The focus shifting range of phased array HIFU transducer is an important safety concern because of the presence of grating lobe in the pre-focal region. However, previous studies were only based on linear acoustic wave model. Materials and methods: The nonlinear wave propagation from a 256-element phased array through multiple layered media was simulated using the angular spectrum approach (ASA) in marching fractional steps with the consideration of diffraction, attenuation and non-linearity effects by a secondorder operator splitting scheme. The distribution of acoustic intensities, temperature elevations, lesion sizes and grating lobe levels were calculated at various axially post-focal shifting distances and driving frequencies. Results: Axially shifting HIFU focus leads to significant increase of the acoustic intensity at the grating lobe, but decrease at the main lobe. The influences on the acoustic field, thermal field and lesion sizes are determined by the shifting distance and driving frequency, and variations can be fit monotonically and linearly. Prediction accuracies by simple regression models are satisfactory. Irreversible tissue coagulation could be generated by the grating lobe at certain conditions. Conclusions: The established nonlinear wave propagation algorithm allows the accurate description of HIFU field and consequently the evaluation of grating lobe and steerability of focus. The influence of focus shifting may be predicted simply. The treatment planning of phased array HIFU ablation could be optimised by setting the appropriate exposure and focus scanning schemes. [ABSTRACT FROM AUTHOR]

Chemotherapeutic drug delivery is often ineffective within solid tumors, but increasing the drug dose would result in systemic toxicity. The use of high-intensity focused ultrasound (HIFU) has the potential to enhance penetration of small molecules. However, operation parameters need to be optimized before the use of chemotherapeutic drugs in vivo and translation to clinical trials. In this study, the effects of pulsed HIFU (pHIFU) parameters (spatial-average pulse-average intensity, duty factor and pulse repetition frequency) on the penetration as well as content of small molecules were evaluated in ex vivo porcine kidneys. Specific HIFU parameters resulted in more than 40 times greater Evans blue content and 3.5 times the penetration depth compared with untreated samples. When selected parameters were applied to porcine kidneys in vivo, a 2.3-fold increase in concentration was obtained after a 2-min exposure to pHIFU. Pulsed HIFU has been found to be an effective modality to enhance both the concentration and penetration depth of small molecules in tissue using the optimized HIFU parameters. Although, performed in normal tissue, this study has the promise of translation into tumor tissue. [ABSTRACT FROM AUTHOR]

Purpose/aim of study: Drug delivery to the ocular posterior segment is of importance, but it is a challenge in the treatment of irreversible blindness disease, such as age-related macular degeneration. Although some methods (i.e. intraocular injection, sustained release by polymer and iontophoresis) have been applied, some technical drawbacks, such as slow rate and damage to the eye, need to be overcome for wide use. Materials and methods: In this study, the feasibility of high-intensity focused ultrasound (HIFU) to enhance the transsclera drug delivery was tested for the first time. One-hundred HIFU pulses with the driving frequency of 1.1 MHz, acoustic power of 105.6 W, pulse duration of 10–50 ms and pulse repetition frequency of 1 Hz were delivered to the freshex vivoporcine sclera specimen. Results: In comparison to the passive diffusion (control), 50-ms HIFU can increase the penetration depth by 2.0 folds (501.7 ± 126.4 µm versus 252.4 ± 29.2 µm) using bicinchoninic acid assay and Rhodamine 6 G fluorescence intensity by 3.1 folds (22.4 ± 12.3 versus 7.1 ± 4.1) and coverage area by 2.6 folds (40.4 ± 9.1% versus 15.8 ± 2.9%). No morphological changes on the sonicated sclera samples were found using a surface electron microscope. Conclusions: In summary, pulsed-HIFU may be an effective modality in the transsclera drug delivery with a high transporting rate and depth.In vivostudies are necessary to further evaluate its performance, including the drug penetration and its possible side effects. [ABSTRACT FROM PUBLISHER]

The acoustic power of high-intensity focused ultrasound (HIFU) is an important parameter that should be measured prior to each treatment to guarantee effective and safe outcomes. A new calibration technique was developed that involves estimating the pressure distribution, calculating the acoustic power using an underwater pressure blast sensor, and compensating the contribution of harmonics to the acoustic power. The output of a clinical extracorporeal HIFU system (center frequency of ~1 MHz, p+ = 2.5–57.2 MPa, p − = −1.8 to −13.9 MPa, I SPPA = 513–22,940 W/cm 2 , −6 dB size of 1.6 × 10 mm: lateral × axial) was measured using this approach and then compared with that obtained using a radiation force balance. Similarities were found between each method at acoustic power ranging from 18.2 W to 912 W with an electrical-to-acoustic conversion efficiency of ~42%. The proposed method has advantages of low weight, smaller size, high sensitivity, quick response, high signal-to-noise ratio (especially at low power output), robust performance, and easy operation of HIFU exposimetry measurement. [ABSTRACT FROM AUTHOR]

High-intensity focused ultrasound (HIFU) is emerging as an effective therapeutic modality in both thermal ablations for solid tumor/cancer and soft-tissue fragmentation. Mechanical and thermal effects, which play an important role in the HIFU treatment simultaneously, are dependent on the operating parameters and may vary with the progress of therapy. Mechanical erosion in the shape of a 'squid,' a 'dumbbell' lesion with both mechanical and thermal lesions, or a 'tadpole' lesion with mechanical erosion at the center and thermal necrosis on the boundary in the transparent gel phantom could be produced correspondingly with the pulse duration of 5-30 ms, which is much longer than histotripsy burst but shorter than the time for tissue boiling, and pulse repetition frequency (PRF) of 0.2-5 Hz. Meanwhile, variations of bubble cavitation (both inertial and stable cavitation) and temperature elevation in the focal region (i.e., z = -2.5, 0, and 2.5 mm) were measured by passive cavitation detection (PCD) and thermocouples during the therapeutic procedure, respectively. Stable cavitation increased with the pulse duration, PRF, and the number of pulses delivered. However, inertial cavitation was found to increase initially and then decrease with long pulse duration and high PRF. Temperature in the pre-focal region is always higher than those at the focal and post-focal position in all tests. Great variations of PCD signals and temperature elevation are due to the generation and persistence of large bubble, which is resistant to collapse and occurs with the increase of pulse duration and PRF. Similar lesion pattern and variations were also observed in ex vivo porcine kidneys. Hyperechoes in the B-mode ultrasound image were comparable to the shape and size of lesions in the dissected tissue. Thermal lesion volume increased with the increase of pulse duration and PRF, but mechanical erosion reached its maximum volume with the pulse duration of 20 ms and PRF of 1 Hz. Altogether, bubble cavitation and thermal field vary with the progress of HIFU treatment with different sonication parameters, which provide insights into the interaction of ultrasound burst with the induced bubbles for both soft tissue fractionation and enhancement in thermal accumulation. Appropriate synergy and monitoring of mechanical and thermal effects would broaden the HIFU application and enhance its efficiency as well as safety. [ABSTRACT FROM AUTHOR]

Abstract: High intensity focused ultrasound (HIFU) is emerging as an effective oncology treatment modality according to the clinical experience in the last decade. The temperature at the focus can reach over 65°C within seconds, denaturing cellular proteins and resulting in coagulative necrosis. HIFU parameters are usually kept the same for each treatment spot in tumor ablation. Because of the thermal diffusion from nearby spots, the lesion size will gradually increase as the HIFU therapy progresses, which leads to insufficient treatment of initial spots and over exposure of later ones. From the viewpoint of the physician, uniform lesions with the least energy exposure and the least energy are preferred in tumor ablation. In this study, an algorithm was developed to determine the number of HIFU pulses delivered to each spot in order to generate uniform lesions that fill the region-of-interest completely. The exposure energies required using different scanning pathways (raster scanning, spiral scanning from the center to the outside, and spiral scanning from the outside to the center), spot spacing (1mm, 2mm, 4mm, and 6mm) and motion time (from 0s to 400s) were compared with each other. It is found that spiral scanning from the outside to the center with spot spacing of 2mm and motion time less than 10s needs the least numbers of pulses or HIFU energy in uniform lesion production with the minimal temperature elevation. In addition, the effects of thermal properties of tissue (i.e., specific heat capacity, convective heat transfer coefficient, and thermal conductivity) on HIFU ablation were investigated in order to determine the HIFU treatment planning for various targets. Uniform lesion production in the transparent gel phantom and ex vivo bovine liver samples using the proposed algorithm proved effective and accord with the simulation for different scanning pathways by an extracorporeal clinical HIFU system. Therefore, dynamically adjusting ultrasound exposure energy can improve the efficacy and safety of HIFU ablation, and the treatment planning depends on the scanning protocol and thermal properties of the target. [Copyright &y& Elsevier]

Abstract: Esophageal and gastric varices are associated with significant morbidity and mortality for cirrhotic patients. The current modalities available for treating bleeding esophageal and gastric varices, namely endoscopic band ligation and sclerotherapy, require frequent sessions to obtain effective thrombosis and are associated with significant adverse effects. A more effective therapy that results in long-term vascular occlusion has the potential to improve patient outcomes. In this study, we investigated a new potential method for inducing long-term vascular occlusion by targeting segments of a rabbit’s auricular vein in vivo with low-duty-cycle, high-peak-rarefaction pressure (9 MPa), pulsed high-intensity focused ultrasound in the presence of intravenously administered ultrasound microbubbles followed by local injection of fibrinogen and a pro-inflammatory agent (ethanol, cyanoacrylate or morrhuate sodium). The novel method introduced in this study resulted in acute and long-term complete vascular occlusions when injecting a pro-inflammatory agent with fibrinogen. Future investigation and translational studies are needed to assess its clinical applicability. [Copyright &y& Elsevier]

Abstract: Because tumors are much larger in size compared with the beam width of high-intensity focused ultrasound (HIFU), raster scanning throughout the entire target is conventionally performed for HIFU thermal ablation. Thermal diffusion affects the temperature elevation and the consequent lesion formation. As a result, the lesion will grow continuously over the course of HIFU therapy. The purpose of this study was to investigate the influence of scanning pathways on the overall thermal lesion. Two new scanning pathways, spiral scanning from the center to the outside and spiral scanning from the outside to the center, were proposed with the same HIFU parameters (power and exposure time) for each treatment spot. The lesions produced in the gel phantom and bovine liver were compared with those using raster scanning. Although more uniform lesions can be achieved using the new scanning pathways, the produced lesion areas (27.5 ± 12.3 mm2 and 65.2 ± 9.6 mm2, respectively) in the gel phantom are significantly smaller (p < 0.05) than those using raster scanning (92.9 ± 11.8 mm2). Furthermore, the lesion patterns in the gel phantom and bovine liver were similar to the simulations using temperature and thermal dose-threshold models, respectively. Thermal diffusion, the scanning pathway and the biophysical aspects of the target all play important roles in HIFU lesion production. By selecting the appropriate scanning pathway and varying the parameters as ablation progresses, HIFU therapy can achieve uniform lesions while minimizing the total delivered energy and treatment time. [Copyright &y& Elsevier]

High-intensity focused ultrasound (HIFU) has been used to ablate solid tumors and cancers. Because of the hypervascular structure of the tumor and circulating blood inside it, the interaction between the HIFU burst and vessel is a critical issue in the clinical environment. Influences on lesion production and the potential of vessel rupture were investigated in this study for the efficiency and safety of clinical ablation. An extracted porcine artery was embedded in a transparent polyacrylamide gel phantom, with bovine serum albumin (BSA) as an indicator of the thermal lesion, and degassed water was driven through the artery sample. The HIFU focus was aligned to the anterior wall, middle of the artery, and posterior wall. After HIFU ablation, the produced lesion was photographically recorded, and then its size was quantified and compared with that in the gel phantom without artery. In addition, the bubble dynamics (i.e., generation, expansion, motion, and shrinkage of bubbles and their interaction with the artery) were captured using high-speed imaging. It was found that the presence of the artery resulted in a decrease in lesion size in both the axial and lateral directions. The characteristics of the lesion are dependent on the focus alignment. Acoustic and hydrodynamic cavitation play important roles in lesion production and interaction with the artery. Both thermal and mechanical effects were found on the surface of the artery wall after HIFU ablation. However, no vessel rupture was found in this ex vivo study. [ABSTRACT FROM AUTHOR]

Highlights • Frequency chirps don’t affect the average acoustic field. • Stronger bubble expansion and cavitation-enhanced heating could be generated. • Lesion production is enhanced in both gel phantom and ex vivo tissue samples. • Such enhancement is preferable for large frequency sweeping rang in a short time. Abstract High-intensity focused ultrasound (HIFU) has become popular in the noninvasive ablation of a variety of solid tumors and cancers with promising clinical outcomes. Its ablation efficiency should be improved for the reduced treatment duration, especially for a large target. The frequency chirps were proposed and investigated for the enhanced lesion production and bubble cavitation at the focus during HIFU ablation. First, a nonlinear wave model was used to simulate the acoustic field using different excitation strategies (at the constant frequency excitation, downward and upward frequency chirps) and subsequently, the bubble dynamics and cavitation-enhanced temperature elevation were calculated by the Gilmore and Bioheat equations, respectively. Then the temperature rises and the produced lesion in the gel phantom were measured by the thermocouple and recorded photographically, respectively. Bubble activities at the focus were measured by passive cavitation detection (PCD) to quantify the scattering and inertial cavitation levels using short-time Fourier-transform (STFT). Finally, the enhanced temperature elevation, lesion production, and bubble cavitation were further confirmed in the ex vivo tissue samples. It is found that the frequency sweeping time plays a more important role in the enhancement of HIFU-produced lesion in the gel phantom while the frequency sweeping range seems more critical in the tissue. Altogether, large frequency sweeping range in a short time is preferable, and the frequency sweeping direction has little influence on the lesion enhancement. [ABSTRACT FROM AUTHOR]

Abstract: Extracorporeal high-intensity focused ultrasound (HIFU) can be used to ablate tissue noninvasively by delivering focused ultrasound energy from an external source. HIFU for clinical treatment of pancreatic cancer has been reported; however, systematic evaluation of the safety and efficacy of pancreatic ablation with HIFU has not been performed. The objectives of this in vivo study are as follows: (1) assess the safety and feasibility of targeting and ablating pancreatic tissue using the FEP-BY02 HIFU system (Yuande Bio-Medical Engineering, Beijing, China); (2) evaluate a method for estimating in situ acoustic treatment energy in an in vivo setting; and (3) identify the optimal treatment parameters that result in safe and effective ablation of the pancreas. The pancreata of 12 common swine were treated in vivo. Prior to therapy, blood was drawn for laboratory analysis. Animals were then treated with extracorporeal HIFU at three different acoustic treatment energies (750, 1000 and 1250 J). Endoscopy was performed prior to and immediately following HIFU therapy to assess for gastric injury. Blood was drawn after completion of the treatment and on days 2 and 7 following treatment to assess for biochemical evidence of pancreatitis. Animals were then euthanized 7 d following treatment and a necropsy was performed to assess for unintended injury and to obtain pancreatic tissue for histology to assess efficacy of HIFU ablation. Histologic scoring of pancreatic tissue changes was performed by a pathologist blinded to the treatment energy delivered. The degree of ablation identified on histology correlated with the treatment energy. No collateral tissue damage was seen at treatment energies of 750 and 1000 J. At 1250 J, thermal injury to the abdominal muscles and gastric ulcers were observed. There were no premature deaths, serious illnesses, skin burns or evidence of pancreatitis on biochemical analysis. HIFU treatment of the pancreas is feasible, safe and can be used to ablate tissue noninvasively. A clinical trial in humans examining the use of extracorporeal HIFU for palliation of pain related to pancreatic cancer is planned. (E-mail: jooha@u.washington.edu) [Copyright &y& Elsevier]