High Intensity Focused Ultrasound Focus Research Articles

Simultaneous measurement of pressure and temperature in a focused ultrasound field with a fiber optic hydrophone

The characterization of high intensity focused ultrasound (HIFU) fields is important for both clinical treatment planning as well as for regulation of HIFU medical devices. In previous work, we have used a 100-μm fiber optic probe hydrophone (FOPH) to measure pressure waveforms from a 2-MHz HIFU source with 42-mm aperture and 44-mm focal length. The formation of shock waves with peak positive pressure of up to 80-MPa were measured and modeled in transparent tissue-mimicking gel phantoms and boiling was achieved in milliseconds [Canney MS, et al., J. Acoust. Soc. Am., 120:3110 (2006)]. In this work, the FOPH was also used to measure temperature changes in tissue phantoms from HIFU at peak focal intensities of 5000-20,000 W/cm2. Temperature measurements were obtained by first low-pass filtering the voltage signal measured from the FOPH to remove the acoustic part of the measurement. Then, calibration of voltage to temperature was performed using results from a separate calibration experiment. Experimental measurements were compared with numerical modeling using a KZK-type model for acoustic propagation coupled with a heat transfer model. In summary, temperatures of 100°C were measured at the HIFU focus in milliseconds, in agreement with modeling [Work supported by NIH DK43881, NSBRI SMS00402, and RFBR.]

Therapeutic potential of stable cavitation: From enhanced drug delivery to faster hemorrhage control

Current studies indicate that mechanical effects of therapeutic ultrasound resulting in a cavitation activity may be advantageous in variety of clinical applications including tumor treatment, treatment of stroke and vascular diseases, targeted gene and drug delivery, and hemorrhage control. Our drug delivery studies using 880 kHz ultrasound have shown that enhancement of drug delivery through the cornea correlated well (R2̂=0.92) with stable cavitation activity. The delivery enhancement ranged from two to ten times and the power of subharmonic ranged form 5 dBm to 20 dBm in the intensity range of 0.2 0.6 W/cm2. Broadband noise, as an indication of inertial cavitation, was also detected at the highest applied intensity. Changes in the front surface layer of the corneal epithelium indicated the presence of both stable and inertial cavitation activity. Our hemostasis studies have shown that introduction of external microbubbles during application of 5.5 MHz high−intensity focused ultrasound (HIFU) led to faster hemorrhage control of solid organ injuries, appearing to result from both stable and inertial cavitation activity at the location of HIFU focus in a bleeding incision. Microbubbles also allowed easier targeting of an incision site under ultrasound guidance, thus facilitating faster localization and sealing of bleeding incisions.

Using the Acoustic Interference Pattern to Locate the Focus of a High-Intensity Focused Ultrasound (HIFU) Transducer

One of the main problems encountered when using conventional B-mode ultrasound (US) for targeting and monitoring purposes during ablation therapies employing high-intensity focused US (HIFU) is the appearance of strong interference in the obtained diagnostic US images. In this study, instead of avoiding the interference noise, we demonstrate how we used it to locate the focus of the HIFU transducer in both in vitro tissue-mimicking phantoms and an ex vivo tissue block. We found that when the B-mode image plane coincided with the HIFU focal plane, the interference noise was maximally converged and enhanced compared with the off-focus situations. Stronger interference noise was recorded when the angle (α) between the US image plane and the HIFU axis was less than or equal to 90°. By intentionally creating a target (group of bubbles) at the 3.5-MHz HIFU focus (7.1 mm in length and 0.7 mm in diameter), the position of the maximal noise convergence coincided well with the target. The differenced between the predicted focus and the actual one (bubbles) on x and z axes (axes perpendicular to the HIFU central axis, Fig. 1) were both about 0.9 mm. For y axis (HIFU central axis), the precision was within 1.0 mm. For tissue block ablation, the interference noise concentrated at the position of maximal heating of the HIFU-induced lesions. The proposed method can also be used to predict the position of the HIFU focus by using a low intensity output scheme before permanent changes in the target tissue were made. (E-mail: wenshiang@gmail.com)

Comparison of pathway in high-intensity focused ultrasound lesion production

High intensity focused ultrasound (HIFU) is being evaluated for noninvasive treatment of solid tumors. The temperature at the HIFU focus can reach over 65<th>°C, denaturing cellular proteins and resulting in coagulative necrosis and lesion formation. One common method for delivering HIFU therapy clinically is using the spot accumulation method that delivers sequential individual treatment spots. Because of thermal diffusion from nearby treatment spots, the size of subsequent lesions will gradually become larger as the HIFU therapy progresses, which may cause insufficient treatment of the initial spots, and over‐treatment of later spots unless parameters are changed during treatment. A new pathway for HIFU treatment is proposed and compared with the conventional sequential path. Modeling, in vitro phantom and ex vivo bovine liver experiments demonstrate that the new treatment path produces more uniform lesions than the conventional treatment path (p<0.05). The relationship between lesion area/volume and delivered ultrasound energy and the dose‐dependent discrepancies between scanning paths were also studied. In addition, the temperature changes in the ex vivo system were measured using a thermocouple array. Altogether, the new treatment path appears to be advantageous for producing more uniform lesions without modifying HIFU parameters during treatment or significantly increasing the scanning time.

Optimization of lesion formation using high-intensity focused ultrasound at large tissue depths

Background: The objective was to determine the parameters to making a sizable, controlled lesion deep within the treated tissue using high‐intensity focused ultrasound (HIFU). High HIFU intensities allow for rapid temperature rises in tissue used for tumor ablation. Methods: Various experiments were conducted manipulating amplitude and treatment time to produce lesions at full focal length (5.2 cm) of a 3.35 MHz HIFU transducer. Beef thigh was used, as it closely resembles the nonuniformity of human tissue unlike phantom‐gels or turkey breasts. Results/Discussion: Inconsistent lesion formation in our experiments showed that deep lesions in a nonuniform medium are not easily created. At 5.2 cm, in situ HIFU intensities dropped to 170–260 W/cm2 (vs. 40,000–60,000 W/cm2 free field). Reflections off fat, fascia, and bubbles formed at the HIFU focus (at higher intensities) often appear to result in prefocal lesion formation (average total depth of 3.8 cm). Lower intensities over longer treatment times (up to 120 s) yielded desirable lesion depth (average depth of 4.5 cm, highest depth of 6.8 cm), showing longer treatments at lower intensity could be the key to precise deep lesions. Lesion volumes ranged from 0.1 to 26.5 cc. Conclusion: The challenges posed by treatment of nonuniform tissues are similar to those to be encountered in clinical applications.

Robotic high intensity focused ultrasound (HIFU) control for tumor treatment

Introduction: Robotic surgery, with more precise and defined movements compared to manual human surgery, is the wave of the future. The purpose of this project is to move the focus of the HIFU transducer using a 3‐axis robotic work cell in order to treat the whole volume of a tumor in a precise manner. Methods: A 3‐axis robotic work cell from Arricks Robotics was chosen based on price ($3300 USD), precision, range of movement, and payload capacity (up to 2Kg). A LabVIEW program serves as the entire surgery interface including movement options, treatment algorithms with up to 25 points within the tumor, and a guidance system via ultrasound imaging and the hyperechoic spot of the HIFU focus. Results: The robotic work cell could achieve 0.5mm per 10mm precision and speeds of 10mm/sec in real‐time within a cell of 180mm by 180mm by 50mm with a HIFU transducer mounted. Testing with native MD‐2xp software has resulted in distance testing with less than 2% error in all three axes (0.7% in X, 1.5% in Y, 1.3% in Z). Conclusion: The final outcome will provide a robust, computer‐assisted, cost‐effective way to perform robotic HIFU surgery.

Biological and physical mechanisms of HIFU-induced hyperecho in ultrasound images

Guidance and monitoring of high intensity focused ultrasound (HIFU) therapy, using ultrasound imaging, has primarily utilized formation of a hyperechoic region at the HIFU focus. We investigated biologic and physical mechanisms of a hyperecho, as well as safety of this phenomenon, using thermal, acoustic and light microscopy observations. Single, short-duration HIFU pulses (30–60 ms) were able to produce a hyperechoic region at the HIFU focus, 2 cm deep in a rabbit thigh muscle. When hyperechoic regions appeared, inertial cavitation was detected in vivo using a custom-made passive cavitation detection system. Light micrographs showed a large number of cavities (approximately 100/mm 3), 1–10 μm in diameter, in a cytoplasm of cells located at the HIFU focus. Blood congestion was observed around a focal region, indicating an injury of microvasculature. Cellular necrosis was observed at 2 d after the treatment, while healing, scar tissue formation and regeneration were observed at 7 d and 14 d. The results indicate that a possibility of adverse tissue effects has to be taken into consideration when the hyperecho formation, induced by very-short HIFU pulses, is used for pretreatment targeting. (E-mail: adasi@u.washington.edu)

Selective reduction of multifetal pregnancy using high‐intensity focused ultrasound in the rabbit model

High-order multifetal pregnancies carry a significant risk of obstetric complications and poor pregnancy outcome. Selective reduction has traditionally been performed using transabdominal and transvaginal ultrasound-guided intracardiac injection of potassium chloride. We have previously shown that high-intensity focused ultrasound (HIFU) can create a coagulative tissue necrosis in the sheep fetus. The objective of this study was to investigate the feasibility of non-invasive selective fetal reduction using HIFU in a rabbit model. A protocol for HIFU-induced tissue coagulation was developed in the rabbit model. The fetal heart was targeted with ultrasound-guided tissue ablation by a HIFU beam. Five time-mated does between 20-29 days' gestation underwent transabdominal fetal cardiac ablation in a total of 11 fetuses. The HIFU system consisted of a 7-MHz high-power transducer, operated at 2000 W/cm2. The fetal heart rate was observed using real-time ultrasound with Doppler flow velocimetry. All lesions were assessed macroscopically and by histological analysis. Severe bradycardia leading to asystole was observed in all targeted fetuses with ultrasound examination. Dissection of fetuses demonstrated a necrotic intrathoracic lesion similar in size to the HIFU focus (approximately 1 x 9 mm). None of the surrounding fetuses was found to have bradycardia during the procedure or a macroscopic lesion on dissection. In this pilot study HIFU seems promising to ablate even highly vascularized tissue in the fetus.

A novel method for estimating the focal size of two confocal high-intensity focused ultrasound transducers

Estimating the focal size and position of a high-intensity focused ultrasound (HIFU) transducer remains a challenge since traditional methods, such as hydrophone scanning or schlieren imaging, cannot tolerate high pressures, are directional, or provide low resolution. The difficulties increase when dealing with the complex beam pattern of a multielement HIFU transducer array, e.g., two transducers facing each other. In the present study we show a novel approach to the visualization of the HIFU focus by using shockwave-generated bubbles and a diagnostic B-mode scanner. Bubbles were generated and pushed by shock waves toward the HIFU beam, and were trapped in its pressure valleys. These trapped bubbles moved along the pressure valleys and thereby delineated the shape and size of the HIFU beam. The main and sidelobes of 1.1- and 3.5 MHz HIFU beams were clearly visible, and could be measured with a millimeter resolution. The combined foci could also be visualized by observing the generation of sustained inertial cavitation and enhanced scattering. The results of this study further demonstrate the possibility of reducing the inertial cavitation threshold by the local introduction of shock wave-generated bubbles, which might be useful when bubble generation and cavitation-related bioeffects are intended within a small region in vivo.

A pulsatile flow phantom for image-guided high-intensity focused ultrasound studies on blood vessels

A pulsatile flow phantom has been developed for controlled studies of acoustic hemostasis and high intensity focused ultrasound (HIFU) effects on blood vessels. The flow phantom consists of an excised carotid artery attached to a pulsatile pump and embedded in an optically and acoustically transparent gel to create an ex vivo model of a human artery. The artery was punctured with a needle to simulate percutaneous vascular injury. A HIFU transducer with a focal distance of 6 cm and a frequency of 3.33 MHz was used to treat the puncture. B-mode and power-Doppler ultrasound were used to locate the site of the puncture, target the HIFU focus, and monitor treatment. Also, the effects of vascular flow on HIFU lesions were studied by treating vessels in the phantom for different times at a variety of flows. In both studies, histology was done on the artery. In nine trials, HIFU was able to provide complete hemostasis in 55 ± 31 s. It is feasible to use the flow phantom to study acoustic hemostasis of blood vessels. Histology shows that the flow in the phantom appears to diminish the vascular damage from HIFU.

Tissue ablation using high-intensity focused ultrasound in the fetal sheep model: potential for fetal treatment

Objective The aim of this study was to investigate the efficacy of high-intensity focused ultrasound (HIFU) ablation of fetal tissue in a sheep model. HIFU can deliver large amounts of thermal energy by using ultrasonic waves to induce tissue necrosis, without damaging intervening tissues. In contrast to diagnostic ultrasound where intensity levels are below 0.1 W/cm 2, HIFU can deliver 1,000 to 10,000 W/cm 2 at the focal spot. Study design A protocol for HIFU-induced tissue coagulation in the fetus was developed in the ovine model. The fetal liver, lung, kidney, muscle, and placenta were targets for ultrasound-guided tissue ablation by a HIFU beam. All lesions were assessed macroscopically and by histologic analysis. Results In all animals, a necrotic lesion, similar in size to the HIFU focus (approximately 1×9 mm), was achieved. The fetal heart rate remained stable immediately after the procedure. Conclusion In conclusion, HIFU ablation seems to be an effective means to coagulate even highly vascularized tissues in the fetus. This procedure shows promise as a transcutaneous, minimally invasive technique to decrease blood flow through fetal tumors or vascular anastomoses. We are currently conducting further studies to refine the HIFU technique and assess safety for fetus and mother.

Bubbles and acoustic image-guided high intensity focused ultrasound

Clinical diagnostic ultrasound (US) can be used to target and to monitor in real-time high-intensity focused ultrasound (HIFU) therapy. In our system, the HIFU transducer (3.5 MHz, 35 mm aperture, 55 mm radius of curvature) and US scan head (several were tested, center frequencies 3–8 MHz) are fixed with the HIFU focus in the imaging plane. HIFU and US are either synchronized real time to relegate interference to the image fringe or HIFU and US are interlaced for nearly real-time imaging. HIFU produces a localized hyperechoic region visible on B-mode US. Coagulatively necrosed lesions produced have similar size, shape, and location to measurements made from the corresponding US images. Thresholds are also comparable. However, in vivo, if HIFU is turned off as soon as hyperecho appears, no lesion is seen (the tissue was fixed within four hours of treatment). Thus, a short HIFU burst can be used to target treatment. Bubbles appear to be largely but perhaps not entirely responsible for the increase in echogenicity. Times for dissipation of the hyperecho and dissolution of a bubble as a function of hydrostatic pressure compare well. Significant overpressure (50 bar) can suppress hyperecho produced by HIFU. [Work supported by NSF, NSBRI, DARPA/ONR, and NIH SBIR.]