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

Abstract

Systems and methods are provided for effectively 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 above method can be implemented using a transducer assembly comprising two or more transmit arrays each operating at a different frequency. An initial focus can be set and updated by transmitting focused ultrasound using a low frequency transmit array. Phase corrections determined from the first iteration can be applied to subsequent high frequency transmit arrays and received signals, with the process repeating until the desired focus or image resolution is achieved.

Description

[0001] This application is a divisional application of application number 201480011908.0, filed on March 4, 2014, entitled "System and method for measuring and correcting ultrasonic phase distortion caused by aberration media".

[0002] Cross-referencing of related patent applications

[0003] This application claims the benefit of U.S. Provisional Patent Application No. 61 / 771,992, filed March 4, 2013, entitled “System and method for measuring and correcting ultrasonic phase distortion caused by aberration media”.

[0004] Statement on Federally Funded Research

[0005] This invention was made with government support under National Institutes of Health licenses EB003268 and EB009032. The government holds specific rights to this invention. Background of the Invention

[0006] The field of this invention relates to systems and methods for focused ultrasound (FUS). Specifically, the invention relates to systems and methods for efficiently transmitting focused ultrasound waves through aberration media, including the skull and other tissues that can produce ultrasound aberrations.

[0007] Transcranial focused ultrasound (TCU) surgery has been clinically studied for the non-invasive treatment of brain disorders, including chronic pain, essential tremor, and primary brain tumors. While this is an attractive treatment option for brain imaging and therapy, TCU encounters poor ultrasound transmission through the skull, which attenuates and diverges the beam. At low frequencies, phase aberration is minimal due to the heterogeneity and irregularities of the skull; however, at high frequencies, phase correction is required to achieve focused ultrasound in the brain. The necessary phase delay for correction can be determined using geometric and bone density information obtained from preoperative computed tomography (CT) scans, based on computer simulations of sound wave propagation through the skull. However, even the simplest computational models can take hours to calculate the phase delay.

[0008] A simple and straightforward method for measuring phase delay through aberration media is to place the ultrasound source at the focal point and use time-of-flight measurements to calculate the phase delay between transducer elements. A non-invasive implementation of this method has used intracranial bubbles as acoustic beacons, generated through acoustic droplet vaporization or transient cavitation. In a study by Gateau et al., computational tomography-based phase correction was used for the initial focusing step, followed by bubble signature-based phase correction to improve transducer array focusing and for beam manipulation. The transducer array used by Gateau et al. had a frequency of 1 MHz, which was too high to create cavitation events without prior simulation-based phase correction. Furthermore, the receiver, a subset of the transmitting elements, is natively sensitive at its driving frequency.

[0009] A study by Haworth et al. proposed that bubble-based phase correction could be performed by first performing ultrasonic processing at low frequencies, then calculating the phase delay using harmonic imaging, and finally refocusing at high frequencies. However, the equipment and strategies for performing such phase correction were not mentioned. In particular, the problem that bubble motion at low frequencies can occur at arbitrary locations within a fairly large emission focusing area, thus complicating target localization errors, was not addressed.

[0010] Therefore, it is desirable to provide systems and methods for efficiently transmitting focused ultrasound through media such as bone. Summary of the Invention

[0011] This invention overcomes the aforementioned deficiencies by providing a system and method for efficiently transmitting focused ultrasound through a medium (such as bone) using an adaptive focusing scheme. The focusing region of the focused ultrasound is iteratively updated to provide an improved focus for penetration through the medium. This method can be achieved by using a transducer assembly comprising two or more transmitting arrays, each operating at a different frequency. An initial focus is set and updated by transmitting focused ultrasound using a low-frequency transmitting array. The phase correction determined in the first iteration is applied to subsequent higher-frequency transmitting arrays, and this process is repeated until the desired focus is obtained.

[0012] One aspect of the present invention provides a method for adjusting the focus of a focused ultrasound beam. An initial focusing region of an ultrasound transducer assembly comprising multiple transmitter arrays, each operating at a different frequency, is defined by setting an initial focus of the transmitter arrays. Ultrasonic energy is delivered to the initial focusing region using one of the transmitter arrays to excite a contrast agent within the initial focusing region. A signal in response to the excited contrast agent within the initial focusing region is then received using the ultrasound transducer array. An image is generated from the received signal, and the center of the initial focusing region is determined from this image. A phase correction value is calculated using the determined center of the initial focusing region and applied to the focused ultrasound transducer assembly to update the initial focus, thereby defining an updated focusing region that is more focused than the initial focusing region. This process is repeated iteratively until the updated focusing region corresponds to the desired focus. During each repetition of this process, ultrasonic energy is delivered to the updated focusing region to excite the contrast agent within the updated focusing region using a different transmitter array operating at a higher frequency than the previous transmitter array.

[0013] Another aspect of the 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 multiplexing circuitry communicating with the integrated transducer units. Each integrated transducer unit includes at least two transducer elements concentrically nested to form the integrated transducer unit. The multiplexing circuitry is configured to connect the transducer elements in each integrated transducer unit to at least one of a transmit line and a receive line.

[0014] Another aspect of the invention is to provide a focused ultrasound system comprising a transducer assembly and a processor in communication with the transducer assembly. The transducer assembly comprises a plurality of transducer arrays, each consisting of individual transducer elements, each 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 focusing region for the transducer assembly and iteratively update this focusing region for each transmitting array in the transducer assembly. In each iteration, the processor selects the transmitting array with the lowest remaining operating frequency and directs the selected transmitting array to excite the initial focusing region of that transmitting array, and directs at least one receiving array to receive signals from the initial focusing region. The processor then reconstructs an image of the focusing 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 transmitting array and the transmitting array with the next highest operating frequency.

[0015] The foregoing and other aspects and advantages of the present invention will be set forth in the following description. In this description, reference will be made to the accompanying drawings, which form part of the description and illustrate preferred embodiments of the invention by way of illustration. However, such embodiments do not necessarily represent the full scope of the invention; therefore, the scope of the invention is defined according to the claims. Attached Figure Description

[0016] Figure 1 This is a block diagram of an example focused ultrasound system;

[0017] Figure 2A This is an example of an integrated transducer unit that includes nested transmitting and receiving transducers;

[0018] Figure 2B This is an example of an integrated transducer unit array;

[0019] Figure 2C This is an example of a multiplexed circuit connected to an integrated transducer unit;

[0020] Figure 2D This is another example of a multiplexed circuit connected to an integrated transducer unit;

[0021] Figure 3 It is an example of a transducer assembly that includes sparsely distributed receiving sensing elements;

[0022] Figure 4 This is a block diagram of an example of a focused ultrasound system configured for transcranial applications;

[0023] Figure 5 This is a flowchart illustrating the steps of an example method for adaptively adjusting the focus of a transducer assembly, wherein the transducer assembly includes two or more emitter arrays operating at different frequencies. Detailed Implementation

[0024] Systems and methods are provided for effectively transmitting focused ultrasound waves through the skull using a focused ultrasound (FUS) system. In particular, designs and methods for adaptive ultrasound focusing through the skull are provided.

[0025] Reference Figure 1An 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 to the object 102, thereby allowing ultrasonic energy to be efficiently delivered from the ultrasonic transducer 106 to the object 102. For example, the housing 108 may be filled with an acoustic coupling medium 112, which 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 that 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 ultrasound transducer 106 is coupled to the positioning system 110 via a support 116. The positioning system 110 is advantageously a triaxial positioning system that provides precise positioning of the ultrasound transducer 106 in three dimensions, and generally may also be a multiaxial positioning system that provides precise positioning of the ultrasound transducer 106 in two or more dimensions or directions.

[0026] Controller 104 typically includes processor 118, signal generator 120, and radio frequency (RF) amplifier 122. Signal generator 120 may include a function generator and is configured to provide a drive signal for guiding the ultrasound transducer 106 to generate ultrasound energy. The drive signal generated by signal generator 120 is amplified by RF amplifier 122 before being received by ultrasound transducer 106. When the FUS system 100 is used during magnetic resonance-guided FUS (MRgFUS) applications, controller 104 may be located inside or outside the magnetic resonance imaging (MRI) system.

[0027] The processor 118 communicates with the signal generator 120 and directs the signal generator 120 to generate a drive signal, which is then transmitted to the ultrasonic transducer 106. As will be described in detail below, the processor 118 can be configured to adjust the nature of the drive signal in order to regulate the ultrasonic energy pressure generated by the transducer 106 according to embodiments of the invention.

[0028] Processor 118 receives acoustic signals from signal detector 114. As will be described in detail below, the feedback information provided by signal detector 114 is used by processor 118 to guide the appropriate adjustment of ultrasonic energy. Processor 118 also communicates with positioning system 110 and is configured to guide positioning system 110 to move the position of ultrasonic transducer 106 during ultrasonic processing. In the case that ultrasonic transducer 106 is a phased array transducer, controller 104 can adjust the phase and / or amplitude of the drive RF signal of each transducer unit to control the position of the focal point.

[0029] Generally, an ultrasonic transducer 106 can be considered as a transducer assembly comprising one or more arrays of ultrasonic transducer elements. Each transducer array may include only transmitting elements, only receiving elements, or both transmitting and receiving elements. For example, a transducer assembly may include multiple integrated transmitting and receiving arrays. For instance, a transducer array may include two or more transmitting arrays operating at different frequencies, and one or more receiving arrays resonating with harmonics or subharmonics of the transmitting arrays. Preferably, the transducer assembly is a complete hemisphere to provide optimal focusing capability. All these arrays may be either fully assembled or sparsely assembled, where a reduced number of transducer elements is preferred.

[0030] 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 such that they are coaxial. For example, the transmitting element 204 may be a circular transducer element nested within an annular receiving element 206. Although Figure 2A and 2B The diagram shows an integrated unit 202 consisting of only two transducer elements. However, it should be noted that the integrated unit 202 can also be constructed to include more than two nested transducer elements, each capable of transmitting, receiving, or both. The integrated unit 202 can be arranged over the transducer assembly 208, such as... Figure 2B As shown. Generally, the frequency of the integrated unit 202 increases from the external transducer elements to the internal transducer elements in order to maintain good directivity at higher frequencies. The lowest emitted ultrasound frequency is preferably about 100-300 kHz, at which the distortion caused by the skull is minimal.

[0031] Reference Figure 2C and 2DThe nested transducer elements in integrated unit 202 are connected to the multiplexer in multiplexing circuit 210. Under the guidance of the processor, the multiplexer can connect the RF transmit signal to any one of the transducer elements capable of emitting ultrasonic energy. Similarly, the multiplexer can connect receiver electronics to any one of the transducer elements capable of detecting acoustic signals. It is also possible to connect multiple transducer elements simultaneously to separate transmit and / or receive lines. 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 this configuration, each transducer element in each integrated transducer unit 202 is connected to a multiplexer that connects the transducer element to both the transmit and receive lines. Figure 2D In this configuration, each integrated transducer unit 202 includes a transducer element connected only to the transmit line via a multiplexing circuit and a transducer element connected to both the transmit and receive lines via 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 through a properly configured multiplexing circuit. It should also be noted that each integrated transducer unit 202 does not need to be connected to the transmit and receive lines in the same manner. Instead, a group of integrated transducer units 202 can be connected to the transmit and receive lines in one configuration (e.g., ...). Figure 2C (as shown in the configuration); another set of transducer units 202 is connected to the transmit and receive lines in another configuration (e.g., Figure 2D (The configuration method shown).

[0032] Reference Figure 3 The transmitting elements 302 and receiving elements 304 in the transducer assembly 304 can also be sparsely distributed across the entire array aperture. In some high-power applications, a large number of transmitting elements are required; however, far fewer receiving elements are needed to map the activity of the contrast agent. To reduce hardware requirements, receiving elements or integrated units can be more sparsely packed within a large number of transmitting elements. The phase delay calculated from the receiving elements can be applied to the surrounding array of transmitting elements propagating ultrasound across the same region on the skull.

[0033] Reference Figure 4 In some cases, the FUS system 400 can be more specifically configured for transcranial ultrasound applications in the human body. In such a system, the subject 402 receives ultrasound energy from a transducer 406 configured to surround the subject's head. For example, the transducer 406 may be an approximately hemispherical array of transducer elements. The 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 the subject 402 can be maintained at an appropriate temperature during treatment.

[0034] The FUS system 400 includes a processor 418 that can communicate with a multichannel amplifier 424 and a multichannel receiver 426. The multichannel amplifier 424 receives drive signals from the processor 418 and then directs transducer elements in the transducer 406 to generate ultrasonic energy. The multichannel receiver 426 receives acoustic signals during ultrasound processing and relays these signals to the processor 418 for processing according to embodiments of the invention. The processor 418 can also be configured to adjust the drive signals in response to acoustic signals received by the multichannel receiver 426. For example, the phase and / or amplitude of the drive signals can be adjusted so that ultrasonic energy is more effectively transmitted through the skull of the object 402 and into the target volume 430 of interest. Additionally, the acoustic signals can be analyzed to determine whether and how the range of the focused area should be adjusted.

[0035] The overall structure of the FUS system for implementing the present invention has been described, and now refers to Figure 5 The diagram illustrates a flowchart of steps illustrating an example method for improving the transmission efficiency of focused ultrasound waves through the skull or other bony structures. This example method is described below for transcranial applications.

[0036] By using geometric focusing and ignoring the contribution of the skull, ultrasound is initially focused onto the brain using low-frequency ultrasound, as shown in step 502. Due to the use of low frequency, the initial focal spot is relatively large. The patient can then be treated with an ultrasound contrast agent, as shown in step 504. This ultrasound contrast agent can be a microbubble contrast agent or a phase-change drop contrast agent, and is preferably applied at an extremely low concentration. For example, the contrast agent concentration is low enough to enable imaging of individual bubbles in the vascular system.

[0037] A low-frequency emission array is then used to excite a single bubble, as shown in step 506. The harmonic emission in response to this excitation is received by one of the receiver arrays and beamformed using phase and amplitude information to generate an initial image of the bubble, as shown in step 508. The initial beamforming only considers geometric delays, not delays caused by the skull. As noted in decision box 510, the excitation and image reconstruction steps are repeated to create an image time series describing bubble activity at the emission focal point. Further contrast agent is applied to the object to the extent necessary.

[0038] By examining the spatial extent of the activity and the intensity of the bubble response, an 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 that 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 transmitting element to improve the transmit focus, as shown in step 516. This process can be selectively repeated to improve the estimates of the transmit and receive phase corrections, as shown in decision box 518.

[0039] Phase correction can then be applied to the transmit array with the next lower frequency, creating an image timing series with the corresponding receive array to determine the spatial range of the transmit focus and finely tune the transmit and receive focus, as shown in step 520. This process can be iterated at each transmit frequency and repeated at increasing frequencies to create a sharp therapeutic focus at high frequencies, as shown in decision box 522.

[0040] In some embodiments, when the bubble signature recorded at the receiver is weak, image quality can be improved by fitting the desired bubble response to the raw data. One implementation may include finding the best fit by cross-correlating a template of the desired bubble response with the raw data on each line. Therefore, in some embodiments, the systems and methods of the present invention include providing one or more desired bubble response templates. Data captured at a low sampling frequency may be upsampled before template fitting to preserve location information.

[0041] This invention provides the ability to perform high-resolution vascular mapping of the brain for diagnostic purposes. This can be achieved by scanning the emission focus through the brain to simultaneously collect aberration signals from microvesicles injected into blood vessels. In this case, emission and reception signal corrections are first derived, and then a three-dimensional image of the vesicles (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 locations, or long ultrasound imaging using the methods described above can be used to form the image. The method of this 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 in brain imaging and therapeutic applications.

[0042] The invention has been described with respect to one or more preferred embodiments. It should be understood that, in addition to those expressly set forth, many equivalents, alternatives, variations and modifications are possible and fall within the scope of the invention.

Claims

1. A focused ultrasound system (100), comprising: Transducer assembly (106) includes: Multiple transmitting arrays consisting of transmitting transducer elements (204), each transmitting array operating at a different frequency; At least one receiving array consisting of receiving transducer elements (206); The processor (118), which communicates with the transducer assembly (106), is configured to: Set the focusing area for the transducer assembly; The focusing region is iteratively updated for each transducer array in the transducer assembly using the following steps: Select the transmitter array with the lowest remaining operating frequency; The selected emission array is guided to excite the contrast agent within its initial focusing region; At least one receiving array is guided to receive signals from the excited contrast agent from the initial focusing region; Reconstruct the image of the focused area from the received signal; Phase correction values ​​are calculated only from the reconstructed image of the focused region; The processor is configured to apply the calculated phase correction value to the selected transmit array and the transmit array having the next highest operating frequency.

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

3. The focused ultrasound system as described in claim 1, wherein, At least one receiver array is sparsely distributed among multiple transmitter arrays.

4. The focused ultrasound system as described in claim 1, wherein, The processor (118) is configured to: The calculated phase correction value is applied to the received signal to form a phase-corrected signal; and Reconstructing the image from the corrected signal.

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

6. The focused ultrasound system as described in claim 4, wherein, The processor (118) is configured to set multiple simultaneously generated focusing areas for the transducer assembly (106) in order to accelerate data acquisition.

7. A processor for adjusting the focal point of a focused ultrasound beam emitted through an aberration medium, the processor being configured to perform the following operations: A focusing region is provided for the transducer assembly (106), the transducer assembly having: Multiple transmitting arrays, each operating at a different frequency and composed of transmitting transducer elements (204); The receiving array is composed of receiving transducer elements (206); The focusing region is iteratively updated for each emitter array in the transducer assembly (106) using the following steps: Select the transmitter array with the lowest remaining operating frequency; The selected emission array is guided to excite the contrast agent within its initial focusing region; At least one receiving array is guided to receive signals from the excited contrast agent from the initial focusing region; Reconstruct the image of the focused area from the received signal; Phase correction values ​​are calculated only from the reconstructed image of the focused region; The calculated phase correction value is applied to the selected transmitter array and the transmitter array with the next highest operating frequency.

8. The processor of claim 7, further configured to perform the following operations: a) Define the initial focusing area of ​​the ultrasonic transducer assembly by setting the initial focus of the transmitting array, wherein the ultrasonic transducer assembly includes multiple transmitting arrays, each with a different operating frequency; b) By using one of a plurality of emission arrays, ultrasound energy is delivered to the initial focusing region to excite the contrast agent previously provided to the initial focusing region; c) Receive signals in response to the excited contrast agent in the initial focusing region by using an ultrasonic transducer array; d) Generate an image from the received signal; e) Determine the center of the initial focus area from the generated image; f) Calculate the phase correction value by using the center of the determined initial focus area; g) The calculated phase correction value is applied to the focused ultrasound transducer assembly to update the initial focus, thereby defining a more focused updated focus area than the initial focus area; h) Repeat steps b)–g) until the updated focus area corresponds to the required focus; In each repetition, different emission arrays from multiple emission arrays operating at higher frequencies than the previous emission array are used to deliver ultrasound energy to a newer focused region to excite the contrast agent in the newer focused region.

9. The processor of claim 8, further configured to perform the following operations: i) A phase-corrected signal is formed by applying the phase correction value calculated in step f) to the signal received in step c); and j) Reconstruct the image from the phase-corrected signal.

10. The processor of claim 9, wherein, The aberration medium is the skull, and the image reconstructed from the phase-corrected signal is a high-resolution image depicting the vascular system.

11. The processor of claim 10, wherein, Step b) includes: when the previously provided contrast agent is present at a sufficiently low concentration, delivering ultrasound energy to the initial focusing area to excite the previously provided contrast agent, 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 processor of claim 11, wherein, Steps b)-j) are repeated over a period of time, such that multiple time-resolved images describing the microbubble motion caused by blood flow are reconstructed in step j).

13. The processor of claim 12, further configured to perform the following operations: Using the time-resolved image reconstructed in step j), at least one of a dynamic blood flow map and a perfusion map is formed.

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