The present technology relates generally to high intensity focused ultrasound. In particular, several embodiments are directed toward methods and systems for non-invasive treatment of tissue using high intensity focused ultrasound therapy.
Minimally invasive and non-invasive therapeutic ultrasound treatments can be used to ablate, necrotize, and/or otherwise damage tissue. High intensity focused ultrasound (“HIFU”), for example, is used to thermally or mechanically damage tissue. HIFU thermal treatments increase the temperature of tissue at a focal region such that the tissue quickly forms a thermally coagulated treatment volume. HIFU treatments can also cause mechanical disruption of tissue with well-demarcated regions of mechanically emulsified treatment volumes that have little remaining cellular integrity.
A current trend in HIFU medical technologies is to use two-dimensional multi-element phased arrays with the elements distributed over a segment of a spherical surface. Each element of such an array is controlled independently, which makes it possible to electronically steer the focus in space, to create a complex field configuration in the form of several foci, and to minimize the heating of acoustic obstacles (for instance, ribs) while maintaining high intensities at the focus. The arrays can also be utilized to improve the quality of focusing in inhomogeneous tissue using time reversal methods, as well as to trace the region of treatment, which shifts due to respiration.
In many HIFU applications, the acoustic intensity in situ can reach several tens of thousands of watts per square centimeter (W/cm2), causing nonlinear propagation effects. Nonlinear effects can result in formation of weak shocks in the ultrasound waveform, which fundamentally change the efficiency of ultrasound thermal action on tissue, and can lead to new biological effects of a non-thermal nature. However, measurement of all the permutations of an array in water is time consuming and difficult to extrapolate to tissue. Numerical experimentation is an important tool in characterizing pressure fields created by HIFU radiators, in developing exposure protocols, and in predicting corresponding HIFU-induced biological effects in tissue. Simulations work for both water and tissue, but full 3D nonlinear modeling is difficult and computationally expensive. Therefore, there is a need to create reliable and effective methods to characterize three-dimensional fields of multi-element HIFU arrays and properly account for the formation of shocks.
The present technology is directed to methods for characterizing nonlinear ultrasound fields and associated systems and devices. In several embodiments, for example, a method of calculating output of a HIFU device comprises treating a target site with a HIFU array having nonlinear propagation effects. In some embodiments, the array comprises a generally spherical segment. The method can further include simulating a field of the array by setting a boundary condition for the array. Setting a boundary condition can include simplifying at least one geometrical aspect of the generally spherical segment (e.g., modeling a multi-element spherical array as a single-element flat transducer). By modeling the nonlinear effects using the simplified boundary condition, effects of the HIFU treatment parameters can be more readily discerned.
Certain specific details are set forth in the following description and in
Referring back to
During treatment, the HIFU source 102 can be positioned proximate to tissue 108, and the focus 120 of the HIFU source 102 can be aligned with at least a portion of a target site 122 within the tissue 108. For example, the HIFU source 102 can be positioned over a patient's kidney, heart, or liver, and the focus 120 can be aligned with infected or otherwise adverse tissue therein. In still other embodiments, a variety of other types of tissue may be treated using the HIFU system 100. Larger target sites 122 can be mechanically fractionated by scanning the HIFU source 102 over the treatment region using either mechanical or electronic scanning. Such scanning and the initial positioning of the HIFU source 102 can be performed manually or mechanically (e.g., using a three-axis positioning system, not shown). The function generator 104 can initiate the pulsing protocol to generate shock waves with amplitudes between approximately 10 MPa and approximately 100 MPa at the focus 120 with the HIFU source 102 having a frequency of approximately 2 MHz. In other embodiments, such as at lower or higher ultrasound frequencies, the shock wave amplitudes of the HIFU source 102 can be greater or smaller. Absorption of ultrasonic energy occurs primarily at the shock front and induces heating of the tissue 108 that can exceed boiling temperature in the tissue 108.
During each HIFU pulse, one or more boiling bubbles can be formed in the tissue. The superheated vapor of the boiling bubbles provides a force pushing outward from the bubble. This repetitive explosive boiling activity and interaction of the ultrasound shock waves with the boiling bubbles emulsifies the tissue 108 at the target site 122 to form a liquid-filled lesion, at least partially devoid of cellular structure, with little to no thermal coagulation within the treated region. The reflection of the shock wave from the surface of these millimeter-sized boiling bubbles can also form cavitation bubbles proximate to the boiling bubble that can also induce mechanical damage to tissue.
The HIFU system 100 can also include systems or devices that detect and monitor tissue ablation initiation and the activity (e.g., heating or bubble activity) in the tissue 108. In the embodiment illustrated in
The HIFU system 100 can also include a passive cavitation detector (“PCD”) 124 that monitors acoustic signals associated with tissue ablation. For example, the PCD 124 can include an acoustic receiver (e.g., an ultrasound transducer) separate from the HIFU source 102, but confocally aligned with the focus 120 of the HIFU source 102 such that the PCD 124 can receive real-time acoustic feedback during HIFU treatment. As shown in
Echogenic ablation activity and/or the thermal effects of the HIFU treatment can also be monitored using separate devices and systems. The HIFU system 100 illustrated in
In the embodiment shown in
The HIFU system 100 can also simulate the shock waves and heating in water or tissue. Resultant modeling can be used to calculate heating from the shock amplitude of the focal waveform, and for extrapolating pressure waveforms at the focus 120 in water to the equivalent waveforms in tissue. One such method for this extrapolation is called “derating,” and is useful for regulatory oversight and HIFU treatment planning. For example, derating can be used to determine values of the nonlinear acoustic field parameters in the tissue region exposed to HIFU (e.g., the target site 122 and the surrounding tissue 108). During the nonlinear derating process, pressure waveforms are measured and/or modeled in water at the focus 120 at various source outputs. The source outputs are then scaled to generate the same focal waveform with the same focal pressure and focal shape in tissue.
The HIFU system 100 can also include a testing apparatus 130 that can assess the extent of mechanical and/or thermal ablation and distinguish among lesion types. In some embodiments, for example, the testing apparatus 130 can send feedback to the function generator 104 or other components of the HIFU system 100 to cause the function generator 104 to select ultrasound parameters designed to achieve a particular type of mechanical or thermal ablation. In other embodiments, the HIFU system 100 can include a different arrangement and/or may not include a number of features recited above.
The present technology includes systems and methods for simulating nonlinear effects in a focal region of a multi-element array based on a simplified model (an “equivalent source”) with a single-element boundary condition.
As will be described in further detail below, the mathematical operations performed on the simplified model can take on various forms in different embodiments of the technology. For example, a “Westervelt model” can include substituting a single, uniformly vibrating (in terms of the pressure and magnitude), spherical element for the array component in the Westervelt equation, thereby decreasing the dimensions of the equation from three-dimensional in spatial coordinates to two-dimensional (axially symmetric). In another embodiment, a Khokhlov-Zabolotskaya-Kuznetsov (“KZK”) model can include substituting a single, uniformly vibrating, flat element (e.g., a single focused piston source) for the array element in the KZK equation. The effective dimensions are again decreased to two, and the KZK equation can be relatively easier/quicker to solve than the more complicated Westervelt equation.
A. The Westervelt Model
As discussed above, in some embodiments, the field of the array can be simulated according to the Westervelt equation, which in the accompanying system of coordinates can be written in the form
Here, p is acoustic pressure, z is the spatial coordinate along the beam axis, τ=t−z/c0, t is time, Δp=∂2p/∂z2+∂2p/∂y2+∂2p/∂x2, x and y are spatial coordinates lateral to z; ρ0, c0, β, and δ are the density, ambient sound speed, nonlinearity coefficient, and absorption coefficient of the medium, respectively. Calculations can be performed for water, and the corresponding physical parameters in Eq. (1) can be as follows: ρ0=1000 kg/m3, c0=1500 m/s, β=3.5, and δ=4.33×10−6 m2/s. The origin of the coordinates corresponded to the center of a spherical segment where individual elements of the array were located so that the point x=0, y=0, z=F corresponded to the geometric focus of the array. Equation (1), which governs the propagation of nonlinear waves in a thermoviscous medium in the positive direction of the z axis, can be used to simulate weakly nonlinear and weakly focused fields generated by diagnostic ultrasound transducers.
To solve the Westervelt equation (1), written in the evolution form in terms of the z coordinate, it is necessary to assign boundary conditions on some initial plane (x, y, z=z0). Since the elements of the array are distributed on the surface of a spherical cup, the field was first calculated on the plane z0=2 cm from the center of the array using the Rayleigh integral. This plane is located near the edge of the array cup, which is at a distance of z=1.85 cm from the array center.
where k=ω/c0 is the wavenumber, ω=2πf, f is the ultrasound frequency, and u({right arrow over (r)}′) is the complex amplitude of the vibration velocity of the radiator surface S. In other embodiments, the boundary condition is set by acoustic holography or other methods.
As discussed above, in several embodiments, multi-element three-dimensional HIFU arrays can induce complex, nonlinear effects in tissue.
To simplify the analysis of the nonlinear effects of the HIFU radiation, the array in the Westervelt equation is substituted by an equivalent single-element focused piston source 330, as illustrated in
B. The KZK Model
In both of the Westervelt and KZK models, at least two parameters must be determined for the single element models: effective aperture and initial pressure that corresponds to a certain output of the array.
In a further embodiment, the results of the KZK model can be used to create a data base or a look-up table with results for the cases that are within the range of typical HIFU sources. For example, the KZK equation can be rewritten in nondimensional form and all physical parameters of any equivalent source can be reduced to only two parameters: linear focusing gain (G) and proportion to the initial pressure amplitude (N). The KZK model can then be run in two parameter space for different G and N combinations, and the results can be stored in a database or look-up table, or presented as curves. A user can find the effective parameters N and G for their array transducer by measuring the axial field at low power and finding the effective aperture and amplitude. The aperture defines G. The low amplitude can be scaled back to the level of interest to find N. The look-up table can then provide information regarding the type and significance of nonlinear effects.
As will be discussed in further detail below with reference to
3. Validation
The accuracy of the numerical solutions obtained with the simplified equivalent source models may be examined by comparing the simulation results with known analytical solutions or numerical simulations performed using other methods.
The modeling systems and methods described herein can offer several advantages over existing technology. For example, the equivalent source models are expected to make it possible to simulate three-dimensional nonlinear fields of focused ultrasound radiators including formation of shocks in the focal region. Test results have shown high accuracy of the developed models, particularly for the focal lobe and several prefocal and postfocal lobes. It is further expected that the technology may be used to solve a broad class of practically important problems of nonlinear medical acoustics. For example, the disclosed technology may be used to perform nonlinear ultrasound characterization of pressure fields of ultrasound HIFU surgical devices in water and/or to calculate ultrasound-induced thermal effects in tissue. Generalization of the algorithm with account for smooth inhomogeneities in the propagation medium may enable more realistic simulations in soft tissues. It is also expected that the present technology will make it possible to model ultrasound exposures in tissue with the presence of acoustic obstacles, e.g., during irradiation through the rib cage. One feature of the algorithms described herein, for example, is the possibility of calculating three-dimensional fields of radiators with complex spatial configuration while maintaining reasonable requirements on the computing resources available.
From the foregoing, it will be appreciated that specific embodiments of the technology have been described herein for purposes of illustration, but that various modifications may be made without deviating from the disclosure. For example, the HIFU system 100 of
This application is a continuation of U.S. Non-Provisional application Ser. No. 13/479,067, filed May 23, 2012, which claims the benefit of pending U.S. Provisional Application No. 61/488,998, filed May 23, 2011, which is incorporated herein by reference in its entirety.
This invention was made with government support under EB007643, awarded by National Institutes of Health (NIH), and under SMST001601, awarded by National Space Biomedical Research Institute (NSBRI). The government has certain rights in the invention.
Number | Date | Country | |
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61488998 | May 2011 | US |
Number | Date | Country | |
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Parent | 13479067 | May 2012 | US |
Child | 15847765 | US |