System and method for measuring and correcting ultrasonic phase distortion caused by aberrant media

Abstract

Systems and methods are provided for efficiently transmitting and receiving focused ultrasound through a medium, such as bone. The focal region of the focused ultrasound is iteratively updated to provide an improved focus through the medium. The method can be implemented by using a transducer assembly comprising two or more transmit arrays each operating at a different frequency. The initial focus may be set and updated by delivering focused ultrasound using a low frequency transmit array. The phase correction determined by the first iteration may be applied to the subsequent high frequency transmit array and the received signal, the process repeating continuously until a desired focus or image resolution is obtained.

Description

This application is a divisional application with application date of March 4, 2014, application number of 201480011908.0, and title of “System and method for measuring and correcting ultrasonic phase distortion caused by aberration medium”. Cross-references to related patent applications

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 61 / 771,992, filed on March 4, 2013, and entitled “SYSTEM AND METHOD FOR MEASURING AND CORRECTING ULTRASONIC PHASE DISTORTION INDUCED BY ABRASIONAL MEDIA”. Statement Regarding Federally Sponsored Research

[0002] This invention was made with government support under Grants EB003268 and EB009032 from the National Institutes of Health. The government has certain rights in this invention. Background of the Invention

[0003] The field of the invention is systems and methods for focused ultrasound (FUS). In particular, the invention relates to systems and methods for efficiently transmitting focused ultrasound through aberrant media, including skull bones and other tissues that may cause ultrasound to aberrate.

[0004] Transcranial focused ultrasound surgery has been clinically investigated for the noninvasive treatment of brain disorders, including chronic pain, essential tremor, and primary brain tumors. Although this is an attractive treatment approach for brain imaging and treatment, transcranial ultrasound suffers from poor ultrasound transmission through the skull, which attenuates and scatters the beam. At low frequencies, phase aberration due to the inhomogeneous and irregular properties of the skull is minimal; at high frequencies, phase correction is required to achieve ultrasound focusing in the brain. The necessary phase delay for correction can be determined from computer simulations of sound wave propagation through the skull, using geometry and bone density information obtained from preoperative computed tomography scans. However, even the simplest computational models still take hours to calculate the phase delay.

[0005] A simple, direct method for measuring phase delay through an aberrated medium is to place an ultrasound source at the focal point and use time-of-flight measurements to calculate the phase delay between transducer elements. Noninvasive implementations of the above methods have used bubbles within the cranial cavity as acoustic beacons, where the bubbles are created by acoustic droplet vaporization or transient cavitation. In a study by Gateau et al., computed tomography-based phase correction was used for the initial focusing step, and then bubble signature-based phase correction was used to improve transducer array focusing and perform beam steering. The frequency of the transducer array used by Gateau et al. was 1 MHz, which is too high to create cavitation events without first using simulation-based phase correction. In addition, the receiver is a subset of the transmitting elements and is natively sensitive at its driving frequency.

[0006] In a study by Haworth et al., it was proposed that bubble-based phase correction could be performed by first sonicating at low frequency, then calculating phase delay using harmonic imaging, and refocusing at high frequency. However, the equipment and strategy for performing such phase correction were not described. In particular, the problem that bubble motion at low frequencies can occur anywhere within the rather large transmit focal zone, thus compounding target localization errors, was not addressed.

[0007]

[0006] It would therefore be desirable to provide systems and methods for effectively transmitting focused ultrasound through a medium, such as bone. Summary of the invention

[0008] The present invention overcomes the aforementioned deficiencies by providing a system and method for effectively transmitting focused ultrasound through a medium (such as bone) using an adaptive focusing scheme. The focal region of the focused ultrasound is iteratively updated to provide an improved focus through the medium. This method can be implemented by using a transducer assembly including two or more transmit arrays each operating at a different frequency. The initial focus is set and updated by delivering focused ultrasound using a low-frequency transmit array. The phase correction determined in the first iteration is applied to the subsequent higher-frequency transmit array, and the process is cycled until the desired focus is obtained.

[0009] One aspect of the present invention provides a method for adjusting the focus of a focused ultrasound beam. An initial focal region of an ultrasound transducer assembly including a plurality of transmit arrays each having a different operating frequency is defined by setting an initial focus of the transmit array. By using one of the plurality of transmit arrays, ultrasound energy may be delivered to the initial focal region to excite a contrast agent in the initial focal region. Then, by using the ultrasound transducer array, a signal responsive to the contrast agent excited in the initial focal region is received. An image is generated from the received signal, and the center of the initial focal region is determined by the image. A phase correction value is calculated by using the determined center of the initial focal region and applied to the focused ultrasound transducer assembly to update the initial focus, thereby defining an updated focal region that is more focused than the initial focal region. The process is iteratively repeated until the updated focal region corresponds to a desired focus. During each repetition of the process, ultrasound energy is delivered to the updated focal region to excite the contrast agent in the updated focal region by using a different transmit array of the plurality of transmit arrays operating at a higher frequency than the previous transmit array.

[0010] Another aspect of the present invention provides a transducer assembly that can be used in a focused ultrasound system. The transducer assembly includes a plurality of integrated transducer units and a multiplexing circuit that communicates with the integrated transducer units. Each integrated transducer unit includes at least two transducer elements that are concentrically nested to form the integrated transducer unit. The multiplexing circuit is configured to connect the transducer elements in each integrated transducer unit to at least one of a transmit line and a receive line.

[0011] Another aspect of the present invention is to provide a focused ultrasound system including a transducer assembly and a processor in communication with the transducer assembly. The transducer assembly includes a plurality of transducer arrays each consisting of transducer elements, each transducer array operating at a different frequency. The transducer assembly may include at least one additional receiving array consisting of receiving transducer elements. The processor is configured to set a focal region for the transducer assembly and iteratively update the focal region for each transmit array in the transducer assembly. In each iteration, the processor selects the transmit array with the lowest remaining operating frequency, and directs the selected transmit array to excite the initial focal region of the transmit array, and directs at least one receive array to receive signals from the initial focal region. The processor then reconstructs an image of the focal region from the received signals, and calculates a phase correction value from the reconstructed image. The processor then applies the calculated phase correction value to the selected transmit array and the transmit array with the next highest operating frequency.

[0012] The foregoing and other aspects and advantages of the present invention will be given in the following description. In the description, reference will be made to the accompanying drawings which form a part of the description and illustrate preferred embodiments of the present invention by way of illustration. However, such embodiments do not necessarily represent the full scope of the present invention and therefore the scope of the present invention is described in accordance with the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 is a block diagram of an example of a focused ultrasound system;

[0014] Figure 2A is an example of an integrated transducer unit including a nested transmitting transducer and a receiving transducer;

[0015] Figure 2B is an example of an integrated transducer unit array;

[0016] Figure 2C is an example of a multiplexing circuit connected to an integrated transducer unit;

[0017] Figure 2D is another example of a multiplexing circuit connected to an integrated transducer unit;

[0018] Figure 3 is an example of a transducer assembly including sparsely distributed receiving sensing elements;

[0019] Figure 4 is a block diagram of an example of a focused ultrasound system configured for transcranial applications;

[0020] Figure 5 is a flow chart setting forth the steps of an example method for adaptively adjusting the focus of a transducer assembly, wherein the transducer assembly includes two or more transmit arrays operating at different frequencies. DETAILED DESCRIPTION

[0021] Systems and methods are provided for efficiently transmitting focused ultrasound through the skull using a focused ultrasound (FUS) system. In particular, ultrasound transducer array designs and methods are provided for adaptive ultrasound focusing through the skull.

[0022] Reference Figure 1, an exemplary focused ultrasound ("FUS") system 100 for delivering focused ultrasound to an object 102 is shown. The FUS system includes a controller 104, an ultrasonic transducer 106, a housing 108, and a positioning system 110. The housing 108 houses the ultrasonic transducer 106 and provides an interface with the object 102 so that ultrasonic energy can be effectively transferred from the ultrasonic transducer 106 to the object 102. By way of example, the housing 108 can be filled with an acoustic coupling medium 112 that allows ultrasonic energy to propagate more efficiently than in air. An exemplary acoustic coupling medium 112 includes water, such as degassed water. Advantageously, the ultrasonic transducer 106 includes a signal detector 114, such as a hydrophone. For example, the signal detector 114 may include a broadband polyvinylidene fluoride (PVDF) hydrophone, such as described by MAO'Reilly and K. Hynynen in the article "A PVDF Receiver for Ultrasound Monitoring of Transcranial Focused Ultrasound Therapy", (IEEE Transactions on Biomedical Engineering, 2010; 57(9): 2286-2294). The ultrasonic transducer 106 is coupled to the positioning system 110 via a bracket 116. The positioning system 110 is advantageously a three-axis positioning system that provides precise positioning of the ultrasonic transducer 106 in three dimensions, and in general, can also be a multi-axis positioning system that provides precise positioning of the ultrasonic transducer 106 in two or more dimensions or directions.

[0023] The controller 104 generally includes a processor 118, a signal generator 120, and a radio frequency (RF) amplifier 122. The signal generator 120 may include a function generator and is configured to provide a drive signal that guides the ultrasound transducer 106 to generate ultrasound energy. The drive signal generated by the signal generator 120 is amplified by the RF amplifier 122 before being received by the ultrasound transducer 106. When the FUS system 100 is used during a magnetic resonance guided FUS (MRgFUS) application, the controller 104 can be positioned inside or outside a magnetic room of a magnetic resonance imaging (MRI) system.

[0024] The processor 118 is in communication with the signal generator 120 and directs the signal generator 120 to generate a drive signal that is delivered to the ultrasonic transducer 106. As will be described in detail below, the processor 118 may be configured to adjust properties of the drive signal in order to adjust the ultrasonic energy pressure generated by the transducer 106 in accordance with embodiments of the present invention.

[0025] The processor 118 receives the acoustic signal from the signal detector 114. As will be described in detail below, the feedback information provided by the signal detector 114 is used by the processor 118 to guide the appropriate adjustment of the ultrasonic energy. The processor 118 is also in communication with the positioning system 110 and is configured to guide the positioning system 110 to move the position of the ultrasonic transducer 106 during the ultrasonic treatment process. In the case where the ultrasonic transducer 106 is a phased array transducer, the controller 104 can adjust the phase and / or amplitude of the driving RF signal of each transducer element to control the position of the focus.

[0026] In general, the ultrasonic transducer 106 can be considered as a transducer assembly including one or more arrays of ultrasonic transducer elements. Each transducer array can include only transmitting elements, or only receiving elements, or both transmitting and receiving elements. For example, the transducer assembly can include multiple integrated transmitting and receiving arrays. For example, the transducer array can include two or more transmitting arrays operating at different frequencies, and one or more receiving arrays resonating with harmonics or sub-harmonics of the transmitting arrays. Preferably, the transducer assembly is a complete hemisphere to provide the best focusing capability. All of these arrays can be fully assembled or sparsely assembled in the case where a reduced number of transducer elements is preferred.

[0027] In one configuration, for example Figure 2A and 2B As shown, the transducer assembly 208 is composed of an integrated unit 202, which includes a transmitting element 204 and a receiving element 206. The transmitting element 204 and the receiving element 206 are arranged in the integrated unit 202 so that they are coaxial. For example, the transmitting element 204 can be a circular transducer element nested in the annular receiving element 206. Although Figure 2A and 2B The integrated unit 202 is shown as being comprised of only two transducer elements, but it should be noted that the integrated unit 202 may also be constructed to include more than two nested transducer elements, each transducer element being capable of transmitting, receiving, or both. The integrated unit 202 may be arranged within the scope of the transducer assembly 208, such as Figure 2B Generally speaking, the frequency of the integrated unit 202 increases from the external transducer element of the integrated unit 202 to the internal transducer element of the integrated unit 202 to maintain good directivity at higher frequencies. The lowest transmitted ultrasound frequency is preferably about 100-300kHz, at which the distortion caused by the skull is minimal.

[0028] Reference Figure 2C and 2D, the nested transducer elements in the integrated unit 202 are connected to a multiplexer in the multiplexing circuit 210, which, under the direction of the processor, can connect the RF transmit signal to any one of the transducer elements that can transmit ultrasonic energy. Similarly, the multiplexer can connect the receiver electronics to any one of the transducer elements that can detect acoustic signals. It is also possible to connect multiple transducer elements to separate transmit and / or receive lines simultaneously. Figure 2C and 2D Two example configurations of possible connections between the integrated transducer unit 202 and the multiplexing circuit 210 are shown. Figure 2C In each integrated transducer unit 202, each transducer element is connected to a multiplexer that connects the transducer element to both the transmit line and the receive line. Figure 2D , each integrated transducer unit 202 includes one transducer element connected to only the transmit line via a multiplexing circuit and one transducer element connected to both the transmit line and the receive line via a multiplexing circuit 210. It should be understood that any suitable combination of connections between the transducer elements in the integrated transducer unit 202 and the transmit and receive lines can be achieved by a suitably configured multiplexing circuit. It should also be noted that each integrated transducer unit 202 need not be connected to the transmit and receive lines in the same manner. Rather, a group of integrated transducer units 202 can be connected to the transmit and receive lines in a configuration (e.g., Figure 2C Another set of transducer units 202 is connected to the transmitting and receiving lines in another configuration (eg Figure 2D configuration shown).

[0029] Reference Figure 3 , the transmit elements 302 and receive elements 304 in the transducer assembly 304 can also be distributed in a sparse arrangement across the array aperture. In some high power applications, a large number of transmit elements are required, however, far fewer receive elements are required to map the activity of the contrast agent. To reduce hardware requirements, the receive elements or integrated units can be more sparsely populated within the large number of transmit elements. The phase delay calculated from the receive element can be applied to the surrounding transmit element group that propagates ultrasound through the same area on the skull.

[0030] Reference Figure 4 In some cases, FUS system 400 may be more specifically configured for transcranial ultrasound applications in humans. In such a system, subject 402 receives ultrasound energy from transducer 406, which is configured to be centered around the subject's head. For example, transducer 406 may be an approximately hemispherical array of transducer elements. FUS system 400 may include a cooling system, such as a sealed water system with active cooling and degassing capabilities, so that the skull and skin of subject 402 can be maintained at a suitable temperature during treatment.

[0031] The FUS system 400 includes a processor 418 that can communicate with a multi-channel amplifier 424 and a multi-channel receiver 426. The multi-channel amplifier 424 receives a drive signal from the processor 418 and then directs the transducer elements in the transducer 406 to produce ultrasonic energy. The multi-channel receiver 426 receives acoustic signals during the ultrasonic process and relays these signals to the processor 418 for processing according to embodiments of the present invention. The processor 418 can also be configured to adjust the drive signal in response to the acoustic signal received by the multi-channel receiver 426. For example, the phase and / or amplitude of the drive signal can be adjusted so that the ultrasonic energy is more effectively transmitted through the skull of the subject 402 and into the target volume of interest 430. In addition, the acoustic signal can be analyzed to determine whether the extent of the focal area should be adjusted and how to adjust it.

[0032] Having described the overall structure of the FUS system implementing the present invention, now refer to Figure 5 , shows a flow chart setting forth the steps of an example method for improving the transmission efficiency of delivering focused ultrasound through the skull or other bony structures. The example method is described below for transcranial applications.

[0033] By using geometric focusing and ignoring the skull contribution, low frequency ultrasound is initially used to focus ultrasound on the brain, as shown in step 502. Due to the use of low frequency, the initial focus is relatively large. The patient can then be administered an ultrasound contrast agent, as shown in step 504. The ultrasound contrast agent can be a microbubble contrast agent or a phase-change drop contrast agent, and is preferably administered at a very low concentration. For example, the contrast agent concentration is low enough to enable imaging of individual bubbles in the vasculature.

[0034] The low frequency transmit array is then used to excite individual bubbles, as shown in step 506. The harmonic emission in response to the excitation is received by one of the receiver arrays and beamformed using the phase and amplitude information to produce an initial image of the bubble, as shown in step 508. The initial beamforming takes into account only geometric delays, not delays caused by the skull. As indicated in decision box 510, the excitation and image reconstruction steps are repeated to create a time series of images describing the bubble activity at the transmit focus. To the extent additional contrast agent is needed, more contrast agent is applied to the subject.

[0035] By examining the spatial extent of the activity and the intensity of the bubble response, the approximate center of the transmit focus can be determined from the image time series, as shown in step 512. Using the radiation from one of the bubble events at this location, phase corrections for the transmit and receive beams can be calculated, as shown in step 514. These phase corrections are then applied to the transmit elements to improve the transmit focus, as shown in step 516. This process can be optionally repeated to improve the estimate of the transmit and receive phase corrections, as shown in decision block 518.

[0036] Phase correction may then be applied to the transmit array with the next lowest frequency, creating a time series of images through the corresponding receive array to determine the spatial extent of the transmit focus, and fine tune the transmit and receive focus, as shown in step 520. Such a process may be iterated at each transmit frequency, and repeated with increasing frequency, to create a sharp treatment focus at high frequencies, as shown in decision block 522.

[0037] In some embodiments, when the bubble signature recorded at the receiver is weak, the image quality can be improved by fitting the expected bubble response to the raw data. One implementation may include finding the best fit by cross-correlating a template of the expected bubble response with the raw data on each line. Thus, in some embodiments, the systems and methods of the present invention include providing one or more expected bubble response templates. Data captured at a low sampling frequency may be upsampled prior to template fitting in order to preserve position information.

[0038] The present invention provides the ability to perform high resolution vascular mapping of the brain for diagnostic purposes. This can be achieved by scanning the transmit focus through the brain while collecting aberration signals from microbubbles injected into the blood vessels. In this case, transmit and receive signal corrections are first derived, and then a three-dimensional image of the bubbles (and thus the vascular system) is formed and tracked in a time-dependent manner. For such imaging, standard short ultrasound imaging can be used to provide time-resolved echo positions, or long ultrasound imaging using the above-mentioned methods can be used to form the image. The method of the present invention can also improve ultrasound imaging of other aberration media, such as the chest, heart, prostate, etc. For example, chest imaging can be performed using a hemispherical array design similar to that used for brain imaging and therapeutic applications.

[0039] Having described the invention in terms of one or more preferred embodiments, it should be understood that many equivalents, alternatives, variations and modifications besides those explicitly set forth are possible and fall within the scope of the invention.

Claims

1. A focused ultrasound system (100), comprising: A transducer assembly (106) comprising: A plurality of transmit arrays formed by transmit transducer elements (204), each transmit array operating at a different frequency; at least one receive array comprised of receive transducer elements (206); A processor (118) in communication with the transducer assembly (106) is configured to: setting a focal region for the transducer assembly; The focal region is iteratively updated for each transducer array in the transducer assembly by the following steps: Selecting the transmit array with the lowest residual operating frequency; directing the selected transmit array to excite an initial focal region of the transmit array; directing at least one receiving array to receive signals from the initial focal region; reconstructing an image of the focused area from the received signals; calculating a phase correction value from the reconstructed image; The calculated phase correction value is applied to the selected transmit array and the transmit array having the next highest operating frequency.

2. The focused ultrasound system of claim 1, further comprising a multiplexing circuit (210) in communication with the transducer assembly (106) and configured to allow switching between the plurality of transmit arrays and the at least one receive array.

3. The focused ultrasound system of claim 1, wherein: At least one receiving array is sparsely distributed among the plurality of transmitting arrays.

4. The focused ultrasound system of claim 1, wherein: The processor (118) is configured to: applying the calculated phase correction value to the received signal to form a phase corrected signal; and An image is reconstructed from the corrected signal.

5. The focused ultrasound system of claim 4, wherein: The processor (118) is configured to scan a focal region of the transducer assembly (106) through a volume of interest while receiving signals from the volume of interest.

6. The focused ultrasound system of claim 4, wherein: The processor (118) is configured to set a plurality of simultaneously generated focal regions for the transducer assembly (106) to expedite data acquisition.

7. A method for adjusting the focus of a focused ultrasound beam transmitted through an aberrated medium, the method comprising: A focal region is provided for a transducer assembly (106), the transducer assembly having: a plurality of transmit arrays, each operating at a different frequency and comprised of transmit transducer elements (204); a receiving array, composed of receiving transducer elements (206); The focal region is iteratively updated for each transmit array in the transducer assembly (106) by: Selecting the transmit array with the lowest residual operating frequency; directing the selected transmit array to excite an initial focal region of the transmit array; directing at least one receiving array to receive signals from the initial focal region; reconstructing an image of the focused area from the received signals; calculating a phase correction value from the reconstructed image; as well as The calculated phase correction value is applied to the selected transmit array and the transmit array having the next highest operating frequency.

8. The method of claim 7, further comprising: a) defining an initial focusing region of an ultrasonic transducer assembly by setting an initial focus of the transmit array, the ultrasonic transducer assembly comprising a plurality of transmit arrays each having a different operating frequency; b) delivering ultrasound energy to the initial focal region by using one of the plurality of transmit arrays to excite a contrast agent previously provided to the initial focal region; c) receiving, by use of an ultrasound transducer array, a signal responsive to the excited contrast agent in the initial focal region; d) generating an image from the received signal; e) determining the center of an initial focus area from the generated image; f) calculating a phase correction value by using the determined center of the initial focus area; g) applying the calculated phase correction value to the focused ultrasound transducer assembly to update the initial focus, thereby defining an updated focus region that is more focused than the initial focus region; h) repeating steps b)–g) until the updated focus area corresponds to the desired focus; During each repetition, ultrasound energy is delivered to a newer focal region using a different one of the plurality of transmit arrays operating at a higher frequency than a previous transmit array to excite contrast agent in the newer focal region.

9. The method of claim 7, further comprising: i) forming a phase corrected signal by applying the phase correction value calculated in step f) to the signal received in step c); as well as j) Reconstruct the image from the phase-corrected signal.

10. The method of claim 9, wherein: The aberrated medium is the skull, and the image reconstructed from the phase-corrected signal is a high-resolution image depicting the vasculature.

11. The method of claim 10, wherein: Step b) comprises delivering ultrasound energy to the initial focal region to excite the previously provided contrast agent when the previously provided contrast agent is present at a sufficiently low concentration such that the signals received in step c) are spatially separated and each signal corresponds to a single microbubble in the contrast agent.

12. The method of claim 11, wherein: Steps b)-j) are repeated over a period of time such that a plurality of time-resolved images describing the movement of the microbubbles due to the blood flow are reconstructed in step j).

13. The method of claim 12, further comprising forming at least one of a dynamic blood flow map and a perfusion map using the time-resolved image reconstructed in step j).

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