Design and characterization of dual-curvature 1.5-dimensional high-intensity focused ultrasound phased-array transducer

A dual-curvature focused ultrasound phased-array transducer with a symmetric control has been developed for noninvasive ablative treatment of tumors. The 1.5-D array was constructed in-house and the electro-acoustic conversion efficiency was measured to be approximately 65%. In vitro experiments demonstrated that the array uses 256 independent elements to achieve 2-D wide-range high-intensity electronic focusing.     

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.     

A cylindrical-section ultrasound phased-array applicator for hyperthermia cancer therapy

A phased-array applicator geometry for deep localized hyperthermia is presented. The array consists of rectangular transducer elements forming a section of a cylinder that conforms to the body portals in the abdominal and pelvic regions. Focusing and scanning properties of the cylindrical-section array are investigated in homogeneous lossy media using appropriate computer simulations. The characteristic focus of this array is shown to be spatially limited in both transverse and longitudinal directions with intensity gain values suitable for deep hyperthermia applications. The ability of the cylindrical-section phased array to generate multiple foci using the field conjugation method is examined. The effect of the grating lobes on the power deposition pattern of the scanned field is shown to be minimal. Steady-state temperature distributions are simulated using a three-dimensional thermal model of the normal tissue layers surrounding a tumor of typical volume. The advantages and the limitations of this array configuration are discussed.     

A method to synchronize high-intensity, focused ultrasound with an arbitrary ultrasound imager

Ultrasound imaging is useful for monitoring high-intensity, focused ultrasound (HIFU) therapy; however, interference on the ultrasound image, caused by HIFU excitation, must be avoided. A method to synchronize HIFU excitation with ultrasound imaging is described here. Synchronization was tested with two unmodified, commercial imagers and two tissue phantoms.     

High-frequency rapid B-mode ultrasound imaging for real-time monitoring of lesion formation and gas body activity during high-intensity focused ultrasound ablation

The goal of this study was to examine the ability of high-frame-rate, high-resolution imaging to monitor tissue necrosis and gas-body activities formed during high-intensity focused ultrasound (HIFU) application. Ex vivo porcine cardiac tissue specimens (n = 24) were treated with HIFU exposure (4.33 MHz, 77 to 130 Hz pulse repetition frequency (PRF), 25 to 50% duty cycle, 0.2 to 1 s, 2600 W/cm(2)). RF data from Bmode ultrasound imaging were obtained before, during, and after HIFU exposure at a frame rate ranging from 77 to 130 Hz using an ultrasound imaging system with a center frequency of 55 MHz. The time history of changes in the integrated backscatter (IBS), calibrated spectral parameters, and echo-decorrelation parameters of the RF data were assessed for lesion identification by comparison against gross sections. Temporal maximum IBS with +12 dB threshold achieved the best identification with a receiver-operating characteristic (ROC) curve area of 0.96. Frame-to-frame echo decorrelation identified and tracked transient gas-body activities. Macroscopic (millimetersized) cavities formed when the estimated initial expansion rate of gas bodies (rate of expansion in lateral-to-beam direction) crossed 0.8 mm/s. Together, these assessments provide a method for monitoring spatiotemporal evolution of lesion and gas-body activity and for predicting macroscopic cavity formation.     

Numerical simulations of heating patterns and tissue temperature response due to high-intensity focused ultrasound

The results of this paper show-for an existing high intensity, focused ultrasound (HIFU) transducer-the importance of nonlinear effects on the space/time properties of wave propagation and heat generation in perfused liver models when a blood vessel also might be present. These simulations are based on the nonlinear parabolic equation for sound propagation and the bio-heat equation for temperature generation. The use of high initial pressure in HIFU transducers in combination with the physical characteristics of biological tissue induces shock formation during the propagation of a therapeutic ultrasound wave. The induced shock directly affects the rate at which heat is absorbed by tissue at the focus without significant influence on the magnitude and spatial distribution of the energy being delivered. When shocks form close to the focus, nonlinear enhancement of heating is confined in a small region around the focus and generates a higher localized thermal impact on the tissue than that predicted by linear theory. The presence of a blood vessel changes the spatial distribution of both the heating rate and temperature.     

In vitro and in vivo brain ablation created by high-intensity focused ultrasound and monitored by MRI

In this paper, magnetic resonance imaging (MRI) is investigated for monitoring small and large lesions created by high-intensity focused ultrasound (HIFU) in freshly excised lamb brain and in rabbit brain in vivo. A single-element spherically focused transducer of 5 cm diameter, focusing at 10 cm and operating at 1 MHz was used. A prototype MRI-compatible positioning device that is used to navigate the transducer is described. The effects of HIFU were investigated using T1-W and T2-W fast spin echo (FSE) and fluid-attenuated inversion recovery (FLAIR). T2-W FSE and FLAIR show better anatomical details within the brain than T1-W FSE, but with T1-W FSE, the contrast between lesion and brain is higher for both thermal and bubbly lesions. The best contrast between lesion and brain with T1-W FSE is obtained with TR above 500 ms, whereas with T2-W FSE, the best contrast is observed between 40 and 60 ms. The maximum contrast to noise ratio (CNR) measured with T1-W FSE was approximately 20. With T2-W FSE, the corresponding CNR was approximately 12. With this system, we were able to create large lesions (by producing overlapping lesions), and it was possible to monitor these lesions with MRI with excellent contrast. The length of the lesions in vivo brain was much higher than the length in vitro, indicating that the penetration in the in vitro brain is limited, possibly by reflection due to trapped bubbles in the blood vessels. This paper demonstrates that HIFU has the potential to treat brain tumors in humans. This could be done either using a single-element transducer with a frequency around 1 MHZ or using a multi-element transducer.     

Pulsed high-intensity focused ultrasound enhances the relative permeability of the blood-tumor barrier in a glioma-bearing rat model

The use of pulsed high-intensity focused ultrasound (HIFU) with an ultrasound contrast agent (UCA) has been shown to disrupt the blood-brain barrier (BBB) noninvasively and reversibly in the targeted regions. This study evaluated the relative permeability of the blood-tumor barrier (BTB) after sonication by pulsed HIFU. Entry into the brain of chemotherapeutic agents is impeded by the BBB even though the permeability of this barrier may be partially reduced in the presence of a brain tumor. F98 glioma-bearing rats were injected intravenously with Evans blue (EB) with or without BTB disruption induced by pulsed HIFU. Sonication was applied at an ultrasound frequency of 1 MHz with a 5% duty cycle, and a repetition frequency of 1 Hz. The accumulation of EB in brain tumor and the tumor-to-contralateral brain ratio of EB were highest after pulsed HIFU exposure. Sonication followed by EB injection showed a tumor-to-contralateral brain ratio in the target tumors which was about 2 times that of the control tumors. This research demonstrates that pulsed HIFU enhances the relative permeability of the BTB in glioma- bearing rats. The results of this pilot study support the idea that further evaluation of other treatment strategies, such as HIFU exposure in addition to combined chemotherapy or repeated pulsed HIFU exposure to increase delivery of drugs into brain tumors, might be useful.     

Multiple-focus ultrasound phased-array pattern synthesis: optimal driving-signal distributions for hyperthermia

A method for computing array element amplitude and phase distributions for direct synthesis of multiple-focus field patterns using ultrasonic phased arrays is shown to be capable of producing desired field levels at a set of control points in the treatment volume. The complex pressure at any of these control points can be chosen to produce the desired power deposition at the point, including reducing the field level to avoid potential hot spots, thus providing a powerful tool for hyperthermia treatment planning. The method also allows the complex excitation vector to be weighted to reduce the dynamic range of the driving signals without disturbing the relative field levels at the control points, allowing near maximum power transfer from the array into the treatment volume.     

Design of focused ultrasound surgery transducers

High-intensity focused ultrasound surgery (FUS) has been developed for the extracorporeal treatment of various benign and malignant soft tissue tumors. The system developed at the Institute of Cancer Research/Royal Marsden (ICR/RM) National Health Service (NHS) Trust incorporates a 150 mm focal length focused bowl transducer operated at 1.7 MHz, and is currently undergoing Phase 1 clinical trials for the treatment of benign prostatic hyperplasia and superficial bladder cancer. However, the application of this transducer is limited by its focal length to a maximum depth of 100 mm, and by power absorption in the skin to a minimum depth of 40 mm. A computer model of acoustic fields, which assumes uniform excitation of the transducer over its entire surface, has previously been published. This has been used both to calculate the intensity in nonattenuating media, and to estimate the absorbed power per unit volume in homogeneous tissues in order to allow determination of the transducer configurations (frequency, focal length, and diameter) necessary for the treatment of both deep (~150 mm) and shallow (~20 mm) soft tissue tumors. These depths encompass the typical range for human tissues which are likely to be treated. Calculations cover the frequency range 0.5-4.5 MHz, focal lengths from 70 to 200 mm, and transducer diameters from 30 to 190 mm. The results show that appropriate transducers can be designed for the noninvasive treatment of tumors in specific organs     

Experimental evaluation of a prototype cylindrical section ultrasound hyperthermia phased-array applicator

A prototype 64-element, 75 degrees cylindrical-section ultrasonic phased-array hyperthermia applicator has been designed and constructed. The ability of this applicator to focus ultrasonic energy at its geometric focus is verified in a water medium. The array is then driven by excitation vectors obtained using the pseudoinverse pattern synthesis method to generate shifted-focus and multiple-focus field patterns. Experimental results of single and multiple-focus patterns at 500 kHz are given and are in good agreement with theory. The results indicate that the main beam in single-focus patterns is generally insensitive to errors in the phases and amplitudes of the particle velocities of the array elements. The effect of such errors is largely exhibited in the sidelobes which, for all practical purposes, remain at levels acceptable for hyperthermia. This is true for both the geometric focus and shifted foci.     

Computationally efficient algorithms for control of ultrasound phased-array hyperthermia applicators based on a pseudoinverse method

Computationally efficient incremental algorithms for application of the pseudoinverse method for ultrasound phased-array field pattern synthesis are discussed and shown to significantly reduce computing effort when more control points should be added to existing subsets of points previously manipulated. These algorithms avoid calculation of inverse matrices, a time-consuming job for microcomputers when the dimensions of the matrices are large. This technique can be used to recursively modify the heating patterns of a phased-array hyperthermia applicator in the clinic.     

The monopole-source solution for estimating tissue temperatureincreases for focused ultrasound fields

The monopole-source solution to the problem of estimating tissue temperature rise generated by a focused ultrasound beam is presented. The acoustic pressure field generated by a focused, continuous-wave ultrasound source using the acoustic monopole-source method is developed. The point-source solution to the linear bio-heat transfer equation is used to calculate the axial, steady-state temperature increase for both circular and rectangular apertures. The results of the circular aperture are compared with the temperature increase calculated using the heated-disc method and are shown to be in substantial agreement. Finally, the temperature increase generated by the circular aperture is compared to that of the rectangular aperture for the same source power, aperture surface area, operating frequency, and medium properties, and it is shown that the rectangular source generates temperature increases less than those of the circular source under these conditions     

A new high intensity focused ultrasound applicator for surgical applications

Improved high-intensity focused ultrasound (HIFU) surgical applicators are required for use in a surgical environment. We report on the performance and characteristics of a new solid-cone HIFU applicator. Previous HIFU devices used a water-filled stand-off to couple the ultrasonic energy from the transducer to the treatment area. The new applicator uses a spherically-focused element and a solid aluminum cone to guide and couple the ultrasound to the tissue. Compared with the water-filled applicators, this new applicator is simpler to set up and manipulate, cannot leak, prevents the possibility of cavitation within the coupling device, and is much easier to sterilize and maintain during surgery. The design minimizes losses caused by shear wave conversion found in tapered solid acoustic velocity transformers operated at high frequencies. Computer simulations predicted good transfer of longitudinal waves. Impedance measurements, beam plots, Schlieren images, and force balance measurements verified strong focusing and suitable transfer of acoustic energy into water. At the focus, the -3 dB beam dimensions are 1.2 mm (axial)×0.3 mm (transverse). Radiation force balance measurements indicate a power transfer efficiency of 40%. In vitro and in vivo tissue experiments confirmed the applicator's ability to produce hemostasis     

Optimisation strategies and justification: an example in uterine artery embolisation for fibroids

Radiation risk has to be justified and optimised. This study discusses the radiation risk of uterine artery embolisation (UAE) for the treatment of fibroids. A total of 70 consecutive UAE dosimetry parameters were assessed. Using Monte Carlo simulation, organ and effective doses and dose conversion coefficients (DCCs) (mSv Gy cm(-2)) were calculated. During UAE optimisation, avoidance of oblique views and use of last-image-hold (LIH) documentation instead of digital subtraction angiography (DSA) were investigated. Mean dose-area product (DAP) was 37.1 Gy cm2 (median 23.7 Gy cm2) and mean fluoroscopy time was 18.4 min (median 16.6 min). Dose values decreased as the study progressed: mean DAP for patients 1-21, 68.5 Gy cm2; patients 22-43, 35.7 Gy cm2; and patients 44-69, 13.0 Gy cm2. Average DCC for DSA image procedures was 0.572, yielding a mean effective dose of 29.6 mSv (median 17.1 mSv). For LIH-only procedures, an average DCC of 0.813 was estimated [using mean effective dose: 10.6 mSv (median 8.1 mSv)].     

Wideband spherically focused PVDF acoustic sources for calibration of ultrasound hydrophone probes

Several broadband sources have been developed for the purpose of calibrating hydrophones. The specific configuration described is intended for the calibration of hydrophones In a frequency range of 1 to 40 MHz. All devices used 25 /spl mu/m film of PVDF bonded to a matched backing. Two had radii of curvatures (ROC) of 25.4 and 127 mm with f numbers of 3.8 and 19, respectively. Their active element diameter was 0.28 in (6.60 mm). The active diameter of the third source used was 25 mm, and it had an ROC of 254 mm and an f number of 10. The use of a focused element minimized frequency-dependent diffraction effects, resulting in a smooth variation of acoustic pressure at the focus from 1 to 40 MHz. Also, using a focused PVDF source permitted calibrations above 20 MHz without resorting to harmonic generation via nonlinear propagation.     

Pathophysiological mechanisms of high-intensity focused ultrasound-mediated vascular occlusion and relevance to non-invasive fetal surgery

High-intensity focused ultrasound (HIFU) is a non-invasive technology, which can be used occlude blood vessels in the body. Both the theory underlying and practical process of blood vessel occlusion are still under development and relatively sparse in vivo experimental and therapeutic data exist. HIFU would however provide an alternative to surgery, particularly in circumstances where serious complications inherent to surgery outweigh the potential benefits. Accordingly, the HIFU technique would be of particular utility for fetal and placental interventions, where open or endoscopic surgery is fraught with difficulty and likelihood of complications including premature delivery. This assumes that HIFU could be shown to safely and effectively occlude blood vessels in utero. To understand these mechanisms more fully, we present a review of relevant cross-specialty literature on the topic of vascular HIFU and suggest an integrative mechanism taking into account clinical, physical and engineering considerations through which HIFU may produce vascular occlusion. This model may aid in the design of HIFU protocols to further develop this area, and might be adapted to provide a non-invasive therapy for conditions in fetal medicine where vascular occlusion is beneficial.     

Threshold dosages for damage to mammalian liver by high intensity focused ultrasound

The threshold dosages for high-intensity focal lesion production were determined at 3 MHz in the cat liver for exposure durations covering the range 0.003-35 s. The liver threshold was found to parallel that for the brain over the range of exposure durations 0.1 to 10 s, but to be more than twice the intensity level, approximately following the relation IT^0.5=460 W-cm²/s², where I is the peak intensity and T is the exposure duration. At shorter exposure durations the threshold curve deviates from this relation, probably due to a change to a transient cavitation mechanism of damage     

1.5-D high intensity focused ultrasound array for non-invasive prostate cancer surgery

The aim of this study is to demonstrate the feasibility of a new spherically curved 1.5-D phased array for the treatment of localized prostatic cancer. The device is designed to conform to the Ablatherm(R) machine (EDAP-Technomed. France), a commercially available machine in which high intensity focused ultrasound (HIFU) treatment for prostate cancer is administered transrectally. It uses high intensity electronically focused ultrasound to steer a beam along two axes, allowing enough depth to be reached to treat large prostates and eliminating two degrees of mechanical movement. Through computer simulation, it was determined that a curved 1.5-D configuration offered the optimal design. Two configurations were then proposed, and their ability to steer a beam within a target volume centered on the geometric focus of the transducer was simulated. An eight-element prototype was constructed to test the piezo-composite material and its electro-acoustical efficiency. Then, an array was constructed, and a multichannel amplifier and control system were added, to permit remote operation. Acoustical and electrical measurements were made to verify performance. Finally, the 1.5-D array was tested in vitro on samples of pig liver to confirm the ability to induce lesions