HIFU Applications Research Articles

High-speed observation of cavitation bubble cloud structures in the focal region of a 1.2 MHz high-intensity focused ultrasound transducer

Cavitation bubble clouds in the focal region of HIFU play important roles in therapeutic applications of HIFU. Temporal evolution and spatial distribution of cavitation bubble clouds generated in the focal region of a 1.2 MHz single element concave HIFU transducer in water are investigated by high-speed photography. It is found that during the initial 600 μs insonation cavitation bubble clouds organize to the “screw-like structure” or “cap-like structure”. The screw-like structure is characterized by a nearly fixed tip at the geometrical focus of the HIFU transducer, and the cap-like structure is marked by a dent formed in the direction of ultrasound transmission. After 600 μs, another two structures are recorded – “streamer structure” and “cluster structure”. The streamer structure is also featured by a nearly fixed bottom position at the focus, while the cluster structure is distinguished by agglomerations of bubbles around the focus.

2123: Therapeutic application of HIFU in inflammatory breast cancer

2123: Therapeutic application of HIFU in inflammatory breast cancer

Active ultrasonic imaging methods for lesion visualization

Several transient and irreversible changes in thermal and mechanical tissue properties are known to occur during lesion formation using HIFU. Increase in tissue absorption, decrease in tissue perfusion, and increase in tissue hardness are all associated with tissue necrosis associated with the application of HIFU at sufficiently high dosage. We have apparatus and algorithms for estimation of these tissue properties before, during, and after lesion formation using HIFU. Imaging data are obtained synchronously with the application of HIFU and processed for tissue property measurement. Absorption rate, shear elastic modulus, and perfusion are measured by application of 1 HIFU pulse of duration 0.1 to 0.2 s and sub-therapeutic intensity levels. The HIFU beam is interrupted for collection of imaging lines to obtain a spatio-temporal displacement map with sufficient temporal resolution for viscoelastic tissue property measurements. A description of the imaging system and synchronization between the HIFU and imaging transducers is given. Data from lesion formation experiments in vitro and in vivo are given and discussed.

Ultrasound imaging for high intensity focused ultrasound therapy

We have investigated the use of ultrasound-based imaging to develop a non-invasive, safe and real-time method of guidance and monitoring for HIFU therapy. HIFU application was synchronized with the imaging frame rate to allow interference-free visualization of the region of interest. The regions treated with HIFU at intensities above the cavitation threshold appear immediately (within 30–60 ms) as hyperechoic structures in ultrasound images, confirmed to be due to microbubble activity at the focus. This HIFU dose is shown to produce minimal tissue damage, in the form of capillary rupture in an area of approximately 0.5 mm around the focus. The appearance of hyperechoic regions is potentially useful for pre-treatment targeting to ensure that the focus is located at the correct spot. The hyperechoic structures persist for 1–2 min, while the microbubbles still remain at the focus, before being absorbed. Microbubbles at the focus also provide a shield for HIFU, to prevent thermal damage of the healthy tissues located post-focally. Challenges of ultrasound-image-guided HIFU are in monitoring the tissue thermal behavior in and around the focus, and follow-up monitoring of tissues treated with HIFU. Ultrasound imaging is developing into a promising method for guidance of HIFU therapy. [Work funded by DoD, NIH.]

A technique for monitoring and controlling cavitation activity during high intensity focused ultrasound application

It has been reported that cavitation can lead to enhanced heating in the focal region of a HIFU source. In order to exploit this heating for in vivo use, it is essential that the cavitation only occur in the focal region. Thus, the onset and evolution of inertial cavitation activity must be monitored and controlled during HIFU therapy. One candidate sensor is a confocally-aligned passive cavitation detector; however this would add complexity to a clinical HIFU applicator. Instead we propose that the HIFU source itself can serve as a monitoring device. The combination of broadband acoustic emissions (inertial cavitation) and backscatter (stable cavities) emanating from the HIFU focus manifests itself as fluctuations of the otherwise constant driving voltage amplitude, providing a convenient means for sensing cavitation activity. We will present results of experiments assessing the feasibility of using the variance in the amplitude of the HIFU drive voltage as a feedback control signal. Success is determined by the shape of the lesion created using supplemental control compared to the shape obtained otherwise. Two independent control parameters were used: the amplitude and the duty cycle of the HIFU. [Work supported by the Department of the Army award DAMD17-02-2-0014.]

Polyacrylamide gel containing egg white as new model for irradiation experiments using focused ultrasound

A polyacrylamide (PAA) gel containing egg white as a new model for irradiation experiments in high-intensity focused ultrasound HIFU is introduced. The gel is transparent except in thermally necrosed regions which are white. The model is similar to, and has the same benefits as, gels containing bovine serum albumin (BSA) protein, but egg is less expensive than BSA. The acoustic properties of the gel are very favorable, similar to those of soft tissues; density 1.0 g/cm 3, sound speed 1540 m/s and acoustic attenuation 0.4 dB/cm at 2 MHz. We illustrate the usefulness of the gel in visualizing HIFU lesions and introduce a new model of gastric submucosal tumor in a rabbit stomach, showing that this gel can be formed into any desired shape. Our PAA gel containing egg white is an attractive candidate for a disposable acoustic material suitable for experimental applications of HIFU. (E-mail: ktakegami-tky@umin.ac.jp)

High-intensity focused ultrasound for liver biopsy hemostasis

In vivo experiments were conducted to demonstrate the feasibility of HIFU application to control postliver biopsy hemorrhage. Yorkshire pigs were anesthetized and their livers were surgically exposed. Core biopsies (n=74) were performed on the exposed hepatic parenchyma with 14-gauge (n=41) and 18-gauge (n=33) core biopsy needles that were inserted 1.5–2 cm deep into the liver. Hemorrhage was determined from the weight of the blood collected from each biopsy puncture site using surgical sponges immediately after biopsy needle retraction. To stop hemorrhage, immediate HIFU was applied to the needle entry site (n=44) after needle retraction. HIFU was generated using a piezoelectric (PZT) transducer (diameter=42 mm, F number=1.2) at 4.23 MHz. Whole-blood clotting times were measured at various times throughout the experiments. Mean blood loss from control biopsy sites using a 14-gauge needle (n=18) was 1.78 g, while mean blood loss using an 18-gauge needle (n=10) was 1.22 g (two 14-gauge-needle control biopsies were excluded). Virtually no blood loss was measured from the biopsy needle entry site after HIFU application for both 14- and 18-gauge-needle biopsies. Ultrasound imaging demonstrated a marked difference between control sites and HIFU-treated sites where successful hemostasis was achieved.

Feasibility of in vivo cardiac HIFU ablation

The potential for cardiac applications of HIFU remains unexamined. In order to create reproducible lesions in a beating heart, it is necessary to maintain focusing at a certain position within moving myocardial tissue. One technique is to use multiple short HIFU exposures (0.2 s) and synchronize them with an EKG signal and respiration. The left ventricular free wall (LVFW) of calf hearts were cut into 4-cm cubes, degassed in phosphate buffer saline (PBS), and heated to 37<th>°C. An 80-mm-diam spherical-cap transducer with a focus of 90 mm was operated at a frequency of 4.67 MHz and a nominal focal point intensity of 26.9 kW/cm2. The transducer was coupled to the LVFW using degassed PBS. First, the effect of pericardial fat, focal depth, and temperature on lesion size was individually evaluated. Then the 0.2-s HIFU exposure was applied 10 to 30 times at 4-s intervals. The same HIFU transducer was applied to an open-chest canine LVFW with the same triggering protocol. Dimensions of all lesions were measured by visual examination of the fresh, unstained tissue. A histopathological examination of the lesion was also performed. The in vivo lesions were created in similar size to those in vitro.

Acoustic hemostasis

The application of HIFU to tissue can result in rapid temperature elevations, so much so that protein denaturization can occur. Not only can these elevated temperatures and denatured proteins induce coagulative necrosis, but they can also result in the cessation of blood supply to a particular region. Indeed, when applied to a site of active bleeding, hemostasis can be induced. A group of us at the University of Washington have considered the application of HIFU to active bleeding and have developed methods and devices that offer considerable promise for use in clinical medicine. A brief review of our work in this area will be presented, including our most recent results. [Work supported in part by the U.S. Army and the NIH.]

Tumor growth reduction and DNA transfer by cavitation-enhanced high-intensity focused ultrasound in vivo

The potential application of high-intensity focused ultrasound (US), HIFU, was investigated for nonthermal gene transfer and tumor ablation. Renal carcinoma (RENCA) tumors were implanted on the hind leg of BALB/c mice and injected with a marker plasmid. Optison® US contrast agent was also injected into the tumor (IT) or into the venous (IV) circulation. HIFU at 1.55 MHz was applied to the tumors with guidance from diagnostic US images. One test of transfection was also performed with lithotripter shock waves. In one set of exposures, tumor volume was followed for 4 days and a β-galactosidase marker plasmid was used for localization of transfected cells. A second set of exposures employed a luciferase marker plasmid for assessing overall transfection after 2 days. Use of 100-ms bursts at 8-MPa peak rarefactional pressure amplitude stopped tumor growth during the 4-day period, compared to a 2.8-fold growth in shams and yielded luciferase expression 34-fold greater than in shams. Longer bursts or higher pressure amplitudes led to decreases in tumor growth, but did not yield increases in transfection. The HIFU results were similar to those of shock waves for cavitation enhanced by IT Optison®. These results should aid in optimizing the application of HIFU for nonthermal tumor treatment.

HIFU applications with feedback control

High intensity focused ultrasound heating is provided by applying therapeutic ultrasonic waves using an array of transducers. Cavitation is detected by using some or all of the transducers in the array to detect ultrasonic waves emanating from or reflected from the patient's body or the interface. A feedback signal is generated based on such detection. If the feedback signal indicates the presence of cavitation, the therapeutic ultrasonic waves are terminated or altered. Obstacles to ultrasound transmission, such as bony structures or bubbles at the interface between the transducer array and the patient can be detected using the same transducers.