Microbubble-enhanced hemorrhage control using high intensity focused ultrasound

Our objective was to investigate whether hemorrhage control can be achieved faster when high-intensity focused ultrasound (HIFU) is applied in the presence of ultrasound contrast agents (UCA) as compared to HIFU only application. Incisions (3 cm long and 0.5 cm deep) were produced in the livers of anesthetized rabbits. UCA Optison (0.18 ml/kg) was injected into the mesenteric vein. A HIFU applicator (5.5 MHz, 6800 W/cm² in situ) was scanned at a rate of 1–2 mm/s in one direction over the incision (with multiple passes if needed), until hemostasis was achieved. Hemostasis times were 59 ± 23 s (n = 21) in the presence of Optison and 70 ± 23 s (n = 29) without Optison. The presence of Optison produced on average 37% reduction in hemostasis times normalized to initial bleeding rates (p < 0.05), as well as 60% faster formation of the coagulum seal over the incision (p < 0.05). Gross and histological observations showed similar appearance of HIFU lesions produced in the presence of Optison and HIFU lesions produced without Optison. Our results suggest potential utility of UCA for increasing efficiency of HIFU-induced hemostasis of solid organ injuries.     

The effect of acoustic absorber's physical parameters on estimating acoustic intensity in high intensity focused ultrasound field using infrared thermometry

The physical parameters of acoustic absorber play an important role in estimating acoustic intensity in high intensity focused ultrasound (HIFU) using infrared ...     

高强度聚焦超声的临床应用

高强度聚焦超声是近几年发展起来的一种新的非介入性肿瘤治疗技术,临床应用越来越广,文章就其在不同肿瘤如前列腺癌、肝癌、胰腺癌、子宫肌瘤等治疗中的应用及进展进行评述。     

Shape-based ultrasound tomography using a Born model with application to high intensity focused ultrasound therapy

A shaped-based ultrasound tomography method is proposed to reconstruct ellipsoidal objects using a linearized scattering model. The method is motivated by the desire to detect the presence of lesions created by high intensity focused ultrasound (HIFU) in applications of cancer therapy. The computational size and limited view nature of the relevant three-dimensional inverse problem renders impractical the use of traditional pixel-based reconstruction methods. However, by employing a shape-based parametrization it is only necessary to estimate a small number of unknowns describing the geometry of the lesion, in this paper assumed to be ellipsoidal. The details of the shape-based nonlinear inversion method are provided. Results obtained from a commercial ultrasound scanner and a tissue phantom containing a HIFU-like lesion demonstrate the feasibility of the approach where a 20 mm x 5 mm x 6 mm ellipsoidal inclusion was detected with an accuracy of around 5%.     

Characterization of cylindrical ultrasonic transducers using acoustic holography

We present the results of studying the vibrational velocity distribution over the surface of cylindrical ultrasound transducers by acoustic holography. We describe two approaches for acoustic holography: the spatial spectrum method and the Rayleigh integral method. In the case of cylindrical sources the spectral method has a specific feature in comparison to the case of quasi-plane sources: small-scale spectrum components having the form of evanescent (nonpropagating) waves near the source, turn into propagating waves at a certain distance from the source. The use of such a mixed type of waves makes it possible to increase the holographic resolution. To conduct holography of cylindrical sources by the Rayleigh integral method, a modification consisting in the superimposing of boundaries on the integration region is proposed. We present the results of numerical simulation and physical experiments on holography of small cylindrical piezoelectric transducers. We demonstrate that the proposed methods of holography make it possible to recover the vibration structure of source surfaces up to order of the wavelength scales.     

A multiple focused probe approach for high intensity focused ultrasound based surgery

To produce deep-seated surgical lesions using ultrasound requires high power and intensity levels at the target sites. Conventionally, large transducers are used which require big apertures and so are generally suitable only for extra-corporeal access. Such transducers also result in strong off-focus maxima, where the resulting hot spots can destroy normal tissue whilst deep-seated large tissue volumes are being ablated. This paper describes a new approach in which it is proposed that multiple probes are used simultaneously, each at a relatively low power, to result in an overlapping focused region of high temperature without strong off-focus hot spots. Robotic techniques could be used to move the individual probes in coordination to sweep out the desired region of tissue ablation. Simulation and planning are the key to quality prediction for high intensity focused ultrasound (HIFU). Simplified two-dimensional and three-dimensional models of HIFU probes have been developed to study the characteristics of various multi-probe configurations. Preliminary simulation results show that the multi-probe system can be arranged successfully to minimise off-focus hot spots. Experimental results are presented which validate the modality and confirm this positive finding. Further prediction studies and planning will be necessary to achieve the most appropriate desired treatment, by varying the pulse duration and spacing.     

Nonlinear absorption in biological tissue for high intensity focused ultrasound

In recent years the propagation of the high intensity focused ultrasound (HIFU) in biological tissue is an interesting area due to its potential applications in non-invasive treatment of disease. The base principle of these applications is the heat effect generated by ultrasound absorption. In order to control therapeutic efficiency, it is important to evaluate the heat generation in biological tissue irradiated by ultrasound. In his paper, based on the Khokhlov-Zabolotkaya-Kuznetsov (KZK) equation in frequency-domain, the numerical simulations of nonlinear absorption in biological tissues for high intensity focused ultrasound are performed. We find that ultrasound thermal transfer effect will be enhanced with the increasing of initial acoustic intensity due to the high harmonic generation. The concept of extra absorption factor is introduced to describe nonlinear absorption in biological tissue for HIFU. The theoretical results show that the heat deposition induced by the nonlinear theory can be nearly two times as large as that predicated by linear theory. Then, the influence of the diffraction effect on the position of the focus in HIFU is investigated. It is shown that the sound focus moves toward the transducer compared with the geometry focus because of the diffraction of the sound wave. The position of the maximum heat deposition is shifted to the geometry focus with the increase of initial acoustic intensity because the high harmonics are less diffraction. Finally, the temperature in the porcine fat tissue changing with the time is predicated by Pennes' equation and the experimental results verify the nonlinear theoretical prediction.     

Preliminary investigations of ultrasound induced acoustic streaming using particle image velocimetry

Particle image velocimetry was used to investigate ultrasound-induced acoustic streaming in a system for the enhanced uptake of substances from the aquatic medium into fish. Four distinct regions of the induced streaming in the system were observed and measured. One of the regions was identified as an preferential site for substance uptake, where the highest velocities in proximity to the fish surface were measured. A positive linear relationship was found between the ultrasound intensity and the maximum streaming velocity, where a unitless geometric factor, specific to the system, was calculated for correcting the numerical relationship between the two parameters. The results are part of a comprehensive study aimed at improving mass transdermal administrations of substances (e.g. vaccines, hormones) into fish from the aquatic medium.     

Spatial structure of high intensity focused ultrasound beams of various geometry

The influence of nonlinear and diffraction effects on distortion of the spatial structure of peak positive and negative pressures in focused acoustic beams was studied for a weakly dissipative propagation medium. The problem was solved numerically based on the Khokhlov-Zabolotskaya-Kuznetsov equation for beams with uniform and Gaussian distributions of the harmonic signal amplitude at the source.     

A derating method for therapeutic applications of high intensity focused ultrasound

Current methods of determining high intensity focused ultrasound (HIFU) fields in tissue rely on extrapolation of measurements in water assuming linear wave propagation both in water and in tissue. Neglecting nonlinear propagation effects in the derating process can result in significant errors. A new method based on scaling the source amplitude is introduced to estimate focal parameters of nonlinear HIFU fields in tissue. Focal values of acoustic field parameters in absorptive tissue are obtained from a numerical solution to a KZK-type equation and are compared to those simulated for propagation in water. Focal wave-forms, peak pressures, and intensities are calculated over a wide range of source outputs and linear focusing gains. Our modeling indicates, that for the high gain sources which are typically used in therapeutic medical applications, the focal field parameters derated with our method agree well with numerical simulation in tissue. The feasibility of the derating method is demonstrated experimentally in excised bovine liver tissue.     

高频聚焦换能器声场的激光测量法

本文描述了一种使用激光测振技术测量高频聚焦换能器声场布的方法，并给出了使用该方法对一种高频聚换能器进行测量的结果，通过理论计算对结果的正确性进行了验证。     

Acoustic power calibration of high-intensity focused ultrasound transducers using a radiation force technique

To address the challenges associated with measuring the ultrasonic power from high-intensity focused ultrasound transducers via radiation force, a technique based on pulsed measurements was developed and analyzed. Two focused ultrasound transducers were characterized in terms of an effective duty factor, which was then used to calculate the power during the pulse at high applied power levels. Two absorbing target designs were used, and both gave comparable results and displayed no damage and minimal temperature rise if placed near the transducer and away from the focus. The method yielded reproducible results up to the maximum pulse power generated of approximately 230 W, thus allowing the radiated power to be calibrated in terms of the peak-to-peak voltage applied to the transducer.     

The use of a micro-bubble agent to enhance rabbit liver destruction using high intensity focused ultrasound

Liver tissues in New Zealand rabbits were ablated using high intensity focused ultrasound (HIFU, 14300 W/cm(2), 1.0 MHz). The animals were intravenously administered 0.2 ml of micro-bubble agent in the experimental (n=20) group and an isovolumetric normal saline solution in the control (n=27) group before HIFU treatment which was performed as a linear scan. In both groups, the preselected tissue volumes were destroyed without harming the overlying tissues. Necrosis rate (NR, cm(3)/s) was used to reflect the ablation efficiency, which was the tissue volume of occurring coagulative necrosis per 1s HIFU exposure. NR was improved in the experimental group (0.0570+/-0.0433 vs 0.0120+/-0.0122, P=0.0002). Pathological studies confirmed that there were no residual intact targets within the exposed volume. These findings suggested that the introduction of the micro-bubble agent enhanced HIFU liver destruction.     

高强度聚焦超声在医学超声领域中的发展与应用

高强度聚焦超声(high intensity focused ultrasound,简称HIFU)作为一种非侵入性、无毒副作用、具有巨大潜力的治疗肿瘤的手段,近年来已经越来越受到国内外学者的广泛关注。HIFU技术能将超声能量聚焦到人体组织的肿瘤内,产生高温,使肿瘤组织温度迅速上升至65℃以上,而发生不可逆转的凝固性坏死,从而达到消融肿瘤组织的目的。目前中国的HIFU肿瘤治疗技术和临床居国际领先。文章对HIFU在医学超声领域中的发展历史、现状和前景进行了探讨。     

Sub-array patterns of spherical-section phased array for high intensity focused ultrasound surgery

The sub-array field patterns of spherical-section phased array were implemented for noninvasive ultrasound surgery of liver-tumor. The sub-array approach included field calculation, pseudo-inverse method and genetic algorithm. The sub-arrays uncovered by ribs according to scanned images normally emitted ultrasound. The results from different sub-arrays demonstrated quite satisfied acoustic performances, which included qualified focus size and intensity level for ultrasound surgery with single-focus and multi-foci patterns. Moreover, the patterns could decrease power accumulation on the ribs, and avoid damaging normal tissues. Thus the sub-array method provides a promising tool for phased array ultrasound propagating through strong obstacles like human rib cage, and it may broaden the therapeutic area, make the surgery safer and more flexible.     

Accurate depth-independent determination of acoustic backscatter coefficients with focused transducers

The accuracy of a method of data reduction for determining acoustic backscatter coefficients was tested using focused transducers and narrow-band pulses. Two phantoms with well-defined scattering properties were the bases of the tests, one having low attenuation and one with tissue-mimicking attenuation. The experimentally determined backscatter coefficients were found to be independent of transducer-to-scattering-volume distance and to agree very well with theoretical values, typically within 10%.     

Measurement of high intensity focused ultrasound fields by a fiber optic probe hydrophone

The acoustic fields of a high intensity focused ultrasound (HIFU) transducer operating either at its fundamental (1.1 MHz) or third harmonic (3.3 MHz) frequency were measured by a fiber optic probe hydrophone (FOPH). At 1.1 MHz when the electric power applied to the transducer was increased from 1.6 to 125 W, the peak positive/negative pressures at the focus were measured to be p(+) = 1.7-23.3 MPa and p(-) = -1.2(-) -10.0 MPa. The corresponding spatial-peak pulse-average (I(SPPA)) and spatial-average pulse-average (I(SAPA)) intensities were I(SPPA) =77-6000 W/cm2 and I(SAPA) = 35-4365 W/cm2. Nonlinear propagation with harmonics generation was dominant at high intensities, leading to a reduced -6 dB beam size (L x W) of the compressional wave (11.5 x 1.8-8.8 1.04 mm) but an increased beam size of the rarefactional wave (12.5 x 1.6-13.2 x 2.0 mm). Enhancement ratio of absorbed power density in water increased from 1.0 to 3.0. In comparison, the HIFU transducer working at 3.3 MHz produced higher peak pressures (p(+) = 3.0-35.1 MPa and p(-) = -2.5(-) - 13.8 MPa) with smaller beam size (0.5 x 4 mm). Overall, FOPH was found to be a convenient and reliable tool for HIFU exposimetry measurement.     

Nonlinear pulsed ultrasound beams radiated by rectangular focused diagnostic transducers

A numerical model for simulating nonlinear pulsed beams radiated by rectangular focused transducers, which are typical of diagnostic ultrasound systems, is presented. The model is based on a KZK-type nonlinear evolution equation generalized to an arbitrary frequency-dependent absorption. The method of fractional steps with an operator-splitting procedure is employed in the combined frequency-time domain algorithm. The diffraction is described using the implicit backward finite-difference scheme and the alternate direction implicit method. An analytic solution in the time domain is employed for the nonlinearity operator. The absorption and dispersion of the sound speed are also described using an analytic solution but in the frequency domain. Numerical solutions are obtained for the nonlinear acoustic field in a homogeneous tissue-like medium obeying a linear frequency law of absorption and in a thermoviscous fluid with a quadratic frequency law of absorption. The model is applied to study the spatial distributions of the fundamental and second harmonics for a typical diagnostic ultrasound source. The nonlinear distortion of pulses and their spectra due to the propagation in tissues are presented. A better understanding of nonlinear propagation in tissue may lead to improvements in nonlinear imaging and in specific tissue harmonic imaging. Published in Russian in Akusticheskiĭ Zhurnal, 2006, Vol. 52, No. 4, pp. 560–570. This article was translated by the authors.     

Energetic balance in an ultrasonic reactor using focused or flat high frequency transducers

In order to undertake irradiation of polymer blocks or films by ultrasound, this paper deals with the measurements of ultrasonic power and its distribution within the cell by several methods. The electric power measured at the transducer input is compared to the ultrasonic power input to the cell evaluated by calorimetry and radiation force measurement for different generator settings. Results obtained in the specific case of new transducer types (composites and focused composites i.e., HIFU: high intensity focused ultrasound) provide an opportunity to conduct a discussion about measurement methods. It has thus been confirmed that these measurement techniques can be applied to HIFU transducers. For all cases, results underlined the fact that measurement of radiation pressure for power evaluation is more adapted to low powers (<15 W) and that measurement by calorimetry is a valid technique for global energy measurements. Composites and monocomponent transducers were compared and it appears that the presence of an adaptation glass plate reduces the efficiency of the monocomponent transducers. The distribution of ultrasonic intensity is qualitatively depicted by sono-chemiluminescence of luminol. Finally, the quantity of energy absorbed by samples placed in the sound field is determined and the temperature distribution monitored as a function of wall distance. This energetic balance allows us to understand the global behaviour of all experimental set-ups made up of a generator–transducer–liquid and sample.     

Differential ultrasonic imaging for the characterization of lesions induced by high intensity focused ultrasound

High intensity focused ultrasound (HIFU) is an effective technique for noninvasive local creating coagulative necrotic lesions in deep target volumes without damage to the overlaying or surrounding tissues. It is very important to detect and evaluate lesions generated by HIFU during treatment procedures. This study describes the development of several differential ultrasonic imaging techniques to characterize lesions based on estimation of relative changes in tissue properties derived from backscattered RF data. A single, spherical HIFU transducer was used to produce lesions in soft tissues. The RF signals were recorded as outputs from a modified diagnostic ultrasound system. After some preprocessing, the integrated backscatter values, which can be used as an indicator of the microstructure and backscattering property of tissues, were calculated before and after HIFU treatment. The differential integrated backscatter values were subsequently used to form images revealing the lesion areas. The differential attenuation imaging with the same RF data was also performed, which has been proposed by a few researchers. The results of the differential integrated backscatter imaging were compared with that of the differential attenuation imaging and the former method offers some advantages over the latter method. The two methods above are both based on spectrum analysis and would spend much computational time. Therefore, some simple digital differential imaging methods, including absolute difference (AD), sum absolute differences (SAD), and sum squared differences (SSD) algorithms, were also proposed to detect HIFU-induced lesions. However, these methods cannot provide the information of the degree of tissue damage. Experiments in vitro bovine muscle and liver validated the method of differential integrated backscatter imaging for the characterization of HIFU-induced lesions. And the AD, SAD, and SSD algorithms can be implemented in real-time during HIFU therapy to visualize the lesions.