The histotripsy spectrum: differences and similarities in techniques and instrumentation.

Since its inception about two decades ago, histotripsy - a non-thermal mechanical tissue ablation technique - has evolved into a spectrum of methods, each with distinct potentiating physical mechanisms: intrinsic threshold histotripsy, shock-scattering histotripsy, hybrid histotripsy, and boiling histotripsy. All methods utilize short, high-amplitude pulses of focused ultrasound delivered at a low duty cycle, and all involve excitation of violent bubble activity and acoustic streaming at the focus to fractionate tissue down to the subcellular level. The main differences are in pulse duration, which spans microseconds to milliseconds, and ultrasound waveform shape and corresponding peak acoustic pressures required to achieve the desired type of bubble activity. In addition, most types of histotripsy rely on the presence of high-amplitude shocks that develop in the pressure profile at the focus due to nonlinear propagation effects. Those requirements, in turn, dictate aspects of the instrument design, both in terms of driving electronics, transducer dimensions and intensity limitations at surface, shape (primarily, the F-number) and frequency. The combination of the optimized instrumentation and the bio-effects from bubble activity and streaming on different tissues, lead to target clinical applications for each histotripsy method. Here, the differences and similarities in the physical mechanisms and resulting bioeffects of each method are reviewed and tied to optimal instrumentation and clinical applications.

Superharmonic Imaging for Medical Ultrasound: a Review.

Ultrasound with harmonics has emerged as an exceptional alternative to competitively low resolution fundamental ultrasound imaging. The use of second harmonic is already a trend now but higher harmonics are also being seen as even better option due to its improved resolution. The resolution improved with frequency but achieves penetration of reduced energy. The cumulative addition of higher harmonics during propagation yields higher harmonics giving better resolution with adequate penetration. This paper summarizes the progress of such similar decade old harmonic ultrasound imaging technique i.e., superharmonic imaging (SHI) geared towards medical field. It comprises of harmonics higher than second harmonic preferably up to 5th harmonic. We conclude that SHI can be an advanced ultrasound imaging with comprehensive high resolution and adequate penetration depth on sole and coded modes.

Derivation of acoustical streaming equations for nonlinear and dispersive fluids.

The equations of streaming generated by an acoustic mod propagating in a nonlinear dispersive medium (exhibiting absorption and dispersion of phase sound speed) are derived with an arbitrarily shaped incident acoustical field assumed. This field may be periodic or non-periodic. A general dispersion model represented by a convolution operator taking into account relaxation effects was taken into account. Making the assumption of a periodic acoustic field from the general streaming equation. The quasi-stationary flow is driven by a force given by the average value of the dispersion operator with respect to the velocity and acoustic pressure fields. In the spectral representation, it is given by the weighted spectral power density distribution of the acoustic field. The weight of the distribution is the dispersion coefficient - the eigenvalue of the dispersion operator. A new result also reveals the effect of the refractive index deviation on the driving force of streaming. The possibility of generalizing the description of streaming in the simplest case of a non-Newtonian fluid was analyzed. The Reiner-Revlin model of a simple liquid was assumed. It was also noted that the streaming model in the Maxwell liquid is analytically solvable. It was found that asymptotic states of streaming in this model and the Navier-Stokes model are identical. The derivations use new methods different from those used so far. They are based on the separation of nonlinear modes in the momentum transport equation and on the properties of the Gauss-Weierstrass function for the Fick diffusion operator. So far, the method of successive approximations has been used. The consistency of the obtained equations with the assumptions was checked. The obtained formulas generalize the known descriptions of the form of forces driving streaming and extend their application to the case of nonlinear propagation.

Analytical solution of the nonlinear equations of acoustic in the form of Gaussian beam.

The nonlinear acoustics equation for a dissipative medium is analytically solved. Continuous wave stimulation and an axisymmetric Gaussian spatial profile of the boundary conditions were assumed. The approximation of the D'Alambert operator by the wave diffusion operator was applied and justified. In this approximation and assuming classical absorption (dispersion), the equation to be solved is presented by the Khokhlov-Zabolotskaya-Kuznetsov model. A sequence of functions describing the spatial distribution of the harmonic components of the disturbance was determined. They are the form of spatially modulated Gauss functions for harmonic wave numbers (frequencies). For a lossless medium a universal numerical sequence describing non-linear interactions and harmonic generations was determined. In other cases, the description of the cooperation of dispersion and non-linear interactions in the harmonic generation process is given by a sequence of functions dependent on the dispersion coefficient and with boundary values given by the universal sequence mentioned above. It was unexpectedly discovered that the influence of geometrical parameters of the beam on nonlinear interactions depends on dispersion, and component of the dispersion, absorption may strengthen harmonic generation. In general, dispersion spatially modulates the amplitude and phase of nonlinear interactions. This is not against the law of conservation of energy. The energy exchange between the fundamental (initiating) component and other harmonics is described. The analytical solution was compared with the numerical one. The numerical solution was obtained in the scheme implementing the full Helmholtz operator (no axial - wave diffusion- approximation).

Experimental and simulation study of harmonic components generated by plane and focused waves.

Although there is increasing interest in the use of plane waves (PW) in high-frame-rate imaging, not much experimental data is available about their behavior in terms of nonlinear propagation. This paper presents a detailed study of fundamental and harmonic components of the ultrasound beam associated to PW transmission from a linear array. Simulations and hydrophone measurements of PW propagation in water were performed and compared to the results obtained for focused waves (FWs) at various levels of peak negative pressure (PNP). Experimental results confirm that, at comparable PNP, the amplitudes of the harmonics reached by PWs are always higher, over extended regions, than those achieved with FW. For example, at MI = 0.2 the PW second harmonic turns out to be 9 dB higher at 25 mm depth (i.e. in the focal region), and 20 dB higher at 40 mm depth. Simulations additionally show that when ultrasound waves propagate through blood or muscle, the situation is in general reversed but, at low MI, the second harmonic amplitude can still be higher in PW than in FW. Furthermore, it is shown that increasing the array aperture size yields higher harmonic growth in PW compared to FW.

Multiple-frequency ultrasonic imaging by transmitting pulsed waves of two frequencies.

PURPOSE: The aim of this study was realization of a broadband measurement system that is capable of effectively carrying out a frequency compound method. In the present method, the secondary wave components of difference and sum frequencies are generated along with the higher harmonic components through the nonlinear interaction of two-frequency ultrasound. A multiple-frequency beam is generated together with the initially radiated frequency components. METHODS: For the structure of a transducer capable of simultaneously radiating two sound waves with different frequencies, a coaxial arrangement of a circular-disc piezoelectric transducer and a ring piezoelectric transducer was designed. The radiating frequencies chosen were 2 and 8 MHz. In addition to the 4-MHz second harmonic sound of the 2-MHz primary sound, sounds of the 6-MHz difference frequency and the 10-MHz sum frequency can be generated. RESULTS: By measuring the acoustic pressure distribution, the formation of a multiple-frequency beam was confirmed. The signal-to-noise ratio in an agar-gel phantom image was increased by 5-6 dB with application of the frequency compound method. The validity of the proposed method was demonstrated through the generation of a human finger image. Further, it was found that the influence of the Doppler effect was small enough that almost all the secondary waves were attributable to the nonlinear propagation of sounds. CONCLUSIONS: A multiple-frequency sound beam was realized by radiating a two-frequency sound. The effectiveness of the presented method was demonstrated through actual imaging.

Numerical simulation of the nonlinear ultrasonic pressure wave propagation in a cavitating bubbly liquid inside a sonochemical reactor.

We investigate the acoustic wave propagation in bubbly liquid inside a pilot sonochemical reactor which aims to produce antibacterial medical textile fabrics by coating the textile with ZnO or CuO nanoparticles. Computational models on acoustic propagation are developed in order to aid the design procedures. The acoustic pressure wave propagation in the sonoreactor is simulated by solving the Helmholtz equation using a meshless numerical method. The paper implements both the state-of-the-art linear model and a nonlinear wave propagation model recently introduced by Louisnard (2012), and presents a novel iterative solution procedure for the nonlinear propagation model which can be implemented using any numerical method and/or programming tool. Comparative results regarding both the linear and the nonlinear wave propagation are shown. Effects of bubble size distribution and bubble volume fraction on the acoustic wave propagation are discussed in detail. The simulations demonstrate that the nonlinear model successfully captures the realistic spatial distribution of the cavitation zones and the associated acoustic pressure amplitudes.

Characterization of nonlinear ultrasound fields of 2D therapeutic arrays.

A current trend in high intensity focused ultrasound (HIFU) technologies is to use 2D focused phased arrays that enable electronic steering of the focus, beamforming to avoid overheating of obstacles (such as ribs), and better focusing through inhomogeneities of soft tissue using time reversal methods. In many HIFU applications, the acoustic intensity in situ can reach thousands of W/cm2 leading to nonlinear propagation effects. At high power outputs, shock fronts develop in the focal region and significantly alter the bioeffects induced. Clinical applications of HIFU are relatively new and challenges remain for ensuring their safety and efficacy. A key component of these challenges is the lack of standard procedures for characterizing nonlinear HIFU fields under operating conditions. Methods that combine low-amplitude pressure measurements and nonlinear modeling of the pressure field have been proposed for axially symmetric single element transducers but have not yet been validated for the much more complex 3D fields generated by therapeutic arrays. Here, the method was tested for a clinical HIFU source comprising a 256-element transducer array. A numerical algorithm based on the Westervelt equation was used to enable 3D full-diffraction nonlinear modeling. With the acoustic holography method, the magnitude and phase of the acoustic field were measured at a low power output and used to determine the pattern of vibrations at the surface of the array. This pattern was then scaled to simulate a range of intensity levels near the elements up to 10 W/cm2. The accuracy of modeling was validated by comparison with direct measurements of the focal waveforms using a fiber-optic hydrophone. Simulation results and measurements show that shock fronts with amplitudes up to 100 MPa were present in focal waveforms at clinically relevant outputs, indicating the importance of strong nonlinear effects in ultrasound fields generated by HIFU arrays.