Systems that emit electromagnetic or sonic waves have powered critical diagnostic and interventional applications. A defining feature of many of these systems, including radar and ultrasonic transducers, is that their dimensions are limited by spatial or hardware constraints. In particular, a dimension D of the transmitting aperture is often relatively small with respect to the distance f within which the system operates. The limited aperture size has led to a fundamental problem of an elongated depth of focus. This problem is severe because the depth of focus is proportional to
Therefore, a reduction in the aperture size leads to a squared increase in the length of the focal region.
Optical imaging systems have overcome this problem by using opposing objective methods with increased aperture size or methods that label or otherwise alter the imaged target or region. However, increasing the aperture size of the system or labeling the targets can be impractical or impossible, especially in domains other than optical imaging. Moreover, interventional or therapeutic applications require a wave-based minimization of the focal volume to specifically manipulate the desired target while sparing surrounding regions.
Accordingly, a method that substantially sharpens the depth of focus without increasing the aperture size of the system would be desirable.
To address this fundamental problem, the disclosure provides a method that substantially sharpens the depth of focus for limited apertures. The method is related to opposing objective methods in that the method uses two opposing apertures but does not require an increase in aperture size. Instead, the method described herein tightens the focal region by superimposing a range of frequencies in space and time as shown in
In one embodiment, the disclosure provides a method for sharpening a focal volume of a therapeutic system or an imaging system. The method comprises applying a plurality of arrays to a target, each array including a plurality of transducers, selecting a group of frequencies, the group of frequencies including a plurality of unique frequencies, assigning one of the frequencies in the group of frequencies to two or more of the plurality of transducers, driving the plurality of transducers to generate a plurality of beamlets, each beamlet including a wave of one of the frequencies in the group of frequencies, and emitting the plurality of beamlets toward the target thereby generating a field of reduced focal volume, wherein the focal volume is improved multifold. In some embodiments, the focal volume is improved by a factor of 10 or more.
In another embodiment, the disclosure provides a therapeutic system comprising a plurality of arrays, each array including a plurality of transducers and a controller electrically coupled to the plurality of transducers. The controller is configured to select a group of frequencies, the group of frequencies including a plurality of unique frequencies, assign one of the frequencies in the group of frequencies to two or more of the plurality of transducers, drive the plurality of transducers to generate a plurality of beamlets, each beamlet including a wave, and emit the plurality of beamlets toward a target thereby generating a focused beam, wherein a focal volume of the beam is improved multifold, and the improvement scales with a frequency bandwidth of the system. In some embodiments, the focal volume of the beam is improved by a factor of 10 or more.
Other aspects of the disclosure will become apparent by consideration of the detailed description and accompanying drawings.
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Before any embodiments are explained in detail, it is to be understood that the embodiments are not limited in application to the details of the configuration and arrangement of components set forth in the following description or illustrated in the accompanying drawings. The embodiments are capable of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein are for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof are meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms “mounted,” “connected,” “supported,” and “coupled” and variations thereof are used broadly and encompass both direct and indirect mountings, connections, supports, and couplings.
In addition, it should be understood that embodiments may include hardware, software, and electronic components or modules that, for purposes of discussion, may be illustrated and described as if the majority of the components were implemented solely in hardware. However, one of ordinary skill in the art, and based on a reading of this detailed description, would recognize that, in at least one embodiment, the electronic-based aspects may be implemented in software (e.g., stored on non-transitory computer-readable medium) executable by one or more processing units, such as a microprocessor and/or application specific integrated circuits (“ASICs”). As such, it should be noted that a plurality of hardware and software-based devices, as well as a plurality of different structural components, may be utilized to implement the embodiments. For example, “servers” and “computing devices” described in the specification can include one or more processing units, one or more computer-readable medium modules, one or more input/output interfaces, and various connections (e.g., a system bus) connecting the components.
The present disclosure provides a wave-based method to overcome the fundamental issue of elongated beams produced by systems with a limited aperture. As disclosed herein, a method, according to an embodiment, is described that enables operators to use existing ultrasonic hardware to greatly sharpen treatment precision. As demonstrated below, no additional hardware is necessary and the improvement in spatial focus is dramatic. The method can be implemented with many of the emerging ultrasonic therapies of the brain, which all need high spatial precision—neuromodulation, local drug release, and transient opening of the blood brain barrier for delivery of large drugs, genes, or stem cells.
MFS is based on a timed emission of waves to achieve constructive interference at the target of interest. Even a small variation in the frequencies emitted from the individual transducers is sufficient to amplify destructive interference near the target, thus leading to substantial sharpening of the depth of focus. The multifrequency emission is necessary for this effect; using the highest frequency within the bandwidth alone produces a much less focal effect as shown in
The multifrequency nature of MFS distinguishes it from previous label-free methods. Nonetheless, MFS incorporates an important concept that has been harnessed in optics on several occasions. Specifically, MFS uses two apertures that oppose each other, akin to opposing objective methods in optical imaging. However, unlike in optics, MFS does not require an increase in the aperture or the solid angle to improve the depth of focus. The improvement is achieved for a fixed, limited aperture by emitting waves of multiple frequencies at defined times to achieve constructive interference at the target while amplifying destructive interference elsewhere. For single frequencies, this geometry produces standing waves (
Label-free improvement in spatial focus can also be achieved using superoscillation. Superoscillation applies complex, optimized lenses to focus waves into focal regions whose size evades the Rayleigh criterion. However, the focal benefit comes at the cost of efficiency—the main lobe receives only a few percent of the total energy, while a large portion of energy is dissipated in side lobes. Therefore, although the concept of superoscillation may prove useful for imaging applications, it is unlikely to serve a major role in therapeutic applications. Compared with superoscillation, in MFS, side lobes are smaller than the main lobe (
Several previous studies, within ultrasonics, have used multiple frequencies to improve spatial resolution. However, these methods, including frequency compounding in elasticity imaging, apply or receive the individual frequency components in separation. The improvement in spatial resolution follows the standard diffraction-limited resolution, in which sharper focus is obtained using higher frequencies. MFS differs fundamentally from these approaches in that MFS emits the distinct frequency components in a controlled spatiotemporal pattern to achieve a specific superposition pattern at the target.
MFS is particularly useful for interventional and therapeutic applications, which generally require a circumscribed beam. For example, ultrasonic transducers produce a characteristic, cigar-shaped beam. When applied for therapeutic purposes such as thermal or mechanical lesioning, opening of the blood-brain barrier, or neuromodulation, this beam geometry poses a risk of harm to unintended targets. MFS overcomes this limitation (
MFS harnesses the available bandwidth of wave-emitting systems. The focal volume improves exponentially with increased bandwidth (
Although the example of
As illustrated in the example of
With continued reference to
As described in further detail below, the controller 101 is configured to selectively and controllably cause the ultrasound transducers 107 in the array(s) to transmit an ultrasound wave and to define/control the parameters of the transmitted ultrasound wave. The controller 101 is also configured to receive output data from other ultrasound transducers 107 in the arrays. In this way, the ultrasound transducers 107 are operated by the controller 101 to transmit and receive ultrasound waves. In some implementations, the controller 101 is configured to electronically communicate with each ultrasound transducer 107 directly while, in other implementations, the controller 101 is indirectly coupled to the plurality of ultrasound transducers 107 through a data acquisition and/or signal routing device (not pictured) that is either incorporated into the controller 101 or provided as a separate additional device.
The controller 101 is also configured to control the operations of other system components of the imaging system 100. The controller 101 includes combinations of hardware and software that are operable to, among other things, control the operation of the system 100, control the output of the transducers 107, etc. The controller 101 includes a plurality of electrical and electronic components that provide power, operational control, and protection to the components and modules within the controller 101 and/or the system 100.
A user interface 109 is included to provide user input to the system 100 and controller 101. The user interface 109 is operably coupled to the controller 101 to control, for example, the output of the arrays 108, 110 (
According to an embodiment, the present disclosure provides a method of sharpening focal volume in electromagnetic- and sonic-based systems.
The MFS concept using simulations that compare the fields produced by MFS with those of traditional, single-frequency approaches was validated. Two spherically focused emitter arrays (as shown in
The ultrasonic arrays 108, 110 were made of the PMN-PT material (e.g., available from Doppler Electronic Technologies, Guangzhou, China), and operated at a fundamental frequency of 650 kHz. The individual elements of the arrays were driven by a programmable system (e.g., Vantage256, available from Verasonics, Kirkland, WA).
The available bandwidth was discretized into an arbitrarily high number of frequencies. Five sets of frequencies were tested. In all cases, the frequencies were equally spaced across the transducers' bandwidth, which ranged from 500 kHz to 800 kHz. The effects of single frequency (650 kHz), three frequencies (500, 650, 800 kHz), five frequencies, ten frequencies, and 252 frequencies (
Each element of the array was randomly assigned one frequency from the set. It was found that randomizing the frequency assignment across the array geometry minimizes the focal volume. Moreover, assigning the frequencies to the elements randomly produced multiple realizations and multiple measurements, which were key for statistical valuations (i.e., producing the confidence error bars in all figures).
Each element was driven for 153 s, i.e., the duration of 100 cycles at 650 kHz. For the elements of the actual hardware, the amplitude output was normalized by the frequency characteristic of each element. This way, all frequencies across the 500-800 kHz bandwidth had comparable amplitude.
Ultrasonic transducers require a certain number of cycles to reach maximum amplitude. To take this hardware constraint into account, the transmission of the waveforms was delayed such that their 10th peak arrived at the target at the same time.
The simulations were performed using Field II. The output was recorded over a 10 mm×40 mm grid in the XY and XZ planes with 0.15 mm spacing. The waveform at each point in the grid was recorded and saved. Since field amplitudes are additive, the total pressure was computed as the sum of the contributions of the individual elements.
The ultrasonic pressure fields were measured using hydrophone field scans. Specifically, the fields were measured using a capsule hydrophone (e.g, HGL-0200, available from Onda) secured to 3-degree-of-freedom programmable translation system (e.g., Aims III, available from Onda). In accord with the simulations, the hydrophone scanned both the XZ and YZ planes, each within 10 mm×40 mm in 0.15 mm steps. Compared to the simulations, which computed the resulting field element-wise, during the actual measurements, all transducers were excited at once to produce the total field.
The maximal pressure P over the time of the simulation was registered at each location, and this value was converted into intensity I using
where Z=1.5 MPa is the acoustic impedance of water. The intensity values were peak-normalized in all plots.
The focal volume was quantified by measuring the total size of the intensity field above half the maximum value. Specifically, the convex hull of the voxels just exceeding the half-maximum intensity was used in both the XY and XZ planes. For each position on the x-axis, the full width half max—the width of the focal volume at half-maximum intensity—in the Y and Z dimension were calculated. Then, these products were integrated over the x axis to get the total volume. In particular, let the functions FWHMy(x) and FWHMz(x) denote the full width half max at position x in the Y and Z dimension, respectively. The focal volume then equals ∫FWHMy(x)FWHMz(x)dx.
All cases used spherically focused phased arrays of 126 elements as shown in
Next, the effect of opposing apertures was tested. The opposing apertures produced the expected standing wave pattern, and reduced the focal volume by a modest 5.3%, to 106.89 mm3 as shown in
These simulations were implemented in ultrasonic hardware and the produced fields were measured using a hydrophone. The resulting fields are shown in
MFS used a ±23% bandwidth (500 kHz to 800 kHz) with respect to the central frequency (650 kHz) used by the single-frequency approaches. The improvements in the focal volume were tested to ensure they were not simply due to the presence of higher frequencies (i.e., frequencies over 650 kHz) in the bandwidth.
Next, the MFS improvements of focus scale with the available bandwidth.
Finally, how the MFS effect depends on specific selections of the frequency distribution within the available bandwidth (
This application is a non-provisional of and claims the benefit of U.S. Provisional Patent Application No. 63/334,277, filed on Apr. 25, 2022 and U.S. Provisional Patent Application No. 63/432,344, filed on Dec. 13, 2022, the entire content of both applications incorporated herein by reference.
This invention was made with government support under NS100986 awarded by the National Institutes of Health (NIH). The government has certain rights in the invention.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2023/019759 | 4/25/2023 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63334277 | Apr 2022 | US | |
| 63432344 | Dec 2022 | US |