Mapping cavitation activity

Abstract

A device for imaging cavitation in an object volume of an object comprises a plurality of transducer elements and a control device. The control device is configured to: control at least a first transducer element of the transducer elements to generate ultrasound with a focal region; receive passive detection signals from a first group of transducer elements and generate a cavitation image of cavitation in the focal region based on the passive detection signals; control at least a second transducer element of the transducer elements to generate reflection imaging ultrasound; receive reflection imaging detection signals from a second group of transducer elements and generate a reflection image based on the reflection imaging detection signals; align the reflection image with a 3D image of the object volume to obtain a transformation between a coordinate system of the first group of transducer elements and a coordinate system of the 3D image; and apply the transformation to the cavitation image to align the cavitation image with the 3D image.

Description

Technical Field

[0001] The present invention relates to therapeutic ultrasound systems and, in particular, to medical mapping and monitoring using acoustic (ultrasound-induced) cavitation. Background Art

[0002] The use of focused ultrasound (FUS) for cancer treatment has several major advantages over other more established treatment modalities: it is inexpensive, non-invasive, and has minimal side effects. However, widespread acceptance of FUS has been hampered by the lack of reliable real-time monitoring systems.

[0003] Above a certain pressure threshold, high-amplitude sound waves propagating through tissue can spontaneously nucleate and excite small bubbles of nanometer or micrometer size, a phenomenon known as acoustic cavitation. Adding or injecting exogenous bubbles as cavitation nuclei, whether they are shell bubbles on the surface of solid particles or stable bubbles [Stride, EP, & Coussios, CC (2010) Cavitation and contrast: The use of bubbles in ultrasound imaging and therapy. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 224 (2), pp. 171-191], low-amplitude sound waves will induce acoustic cavitation in the nuclei, thereby lowering the pressure threshold. Depending on the desired application, cavitation bubbles can be used to produce the desired biological effects. In the case of tissue ablation, these biological effects may lead to thermal necrosis or mechanical separation of tissue. In drug delivery, this could be cavitation-induced microfluidics or micropumping, vasculature permeation, and cell poration, all of which facilitate or enhance the transport of unmodified drugs across tissue membranes, or act directly to disrupt drug-loaded vehicles for targeted drug delivery.

[0004] The bubbles can also re-emit part of the incident ultrasound in a frequency range different from the FUS excitation frequency, which is useful for two reasons. First, the broadband acoustic emissions associated with this acoustic cavitation can serve as an indicator or surrogate marker of medical effectiveness for ablation and drug delivery. Second, the radiation has higher frequency components than the original FUS source and is more easily absorbed by the surrounding tissue, thereby enhancing heat deposition in thermal ablation [Coussios CC, Farny CH, Haar GT, Roy RA, "Role of acoustic cavitation in the delivery and monitoring of cancer treatment by high-intensity focused ultrasound (HIFU)", International Journal of Hyperthermia, Vol. 23, pp. 105-120, 2007]. Although the field of FUS broadly covers all biomedical applications and system configurations related to focused ultrasound, when the amplitude or intensity of the incident ultrasound is higher than that which can be achieved by diagnostic ultrasound imaging systems, a more specific term is often used: high-intensity focused ultrasound (HIFU).

[0005] WO20100052494 discloses a system for imaging acoustic cavitation areas during FUS treatment. However, while the system can effectively image cavitation in real time, it does not describe any way to determine the location of the cavitation in the patient's reference frame (i.e., relative to the patient's anatomy). Since cavitation activity is a predictor of drug delivery efficacy and safety in mechanical or thermal ablation situations, the ability to image and visualize cavitation in 3D has potential benefits in improved medical decision-making and post-treatment evaluation, particularly when 3D volumetric images of the patient (such as X-ray or MR images) typically have higher resolution and higher contrast than ultrasound imaging, allowing cavitation to be shown in high-quality 3D images. Summary of the invention

[0006] The present invention provides an apparatus for imaging cavitation in an imaging volume of an object. The apparatus includes a plurality of transducer elements and a control device. The control device is configured to: control at least a first transducer element of the transducer elements to generate ultrasound with a focal region, the ultrasound may be a therapeutic ultrasound; receive a passive detection signal from a first group of transducer elements, and generate a cavitation image of the cavitation in the focal region according to the passive detection signal; control at least a second transducer element of the transducer elements to generate reflection imaging ultrasound; receive a reflection imaging detection signal from a second group of the transducer elements, and generate a reflection image according to the reflection imaging detection signal; align the reflection image of the object volume with the 3D image to obtain a transformation between the coordinate system of the first group of transducer elements and the coordinate system of the 3D image; and apply the transformation to the cavitation image to align the cavitation image with the 3D image.

[0007] The reflection imaging may be pulse echo imaging, such as B-mode ultrasound imaging, contrast-enhanced ultrasound, pulse inversion ultrasound, or harmonic ultrasound imaging.

[0008] At least a first one of the transducer elements is configured to generate focused ultrasound, and may be a geometrically focused transducer, such as a geometrically focused transducer array with a fixed focus, a geometrically focused transducer array with a static focus that can be electronically moved or steered, or a linear or planar transducer array that may not be perfectly straight or flat, but in which all or substantially all of the electrons are focused. Thus, focusing may be provided geometrically, or electronically, or by a combination of both.

[0009] The first transducer element may be one of the first group of transducer elements, or one of the second group of transducer elements, or not one of either group. Similarly, the second transducer element may be one of the first group of transducer elements, or one of the second group of transducer elements, or not one of either group.

[0010] The first group of transducer elements may be in a fixed position relative to the second group of transducer elements.

[0011] The system may further comprise a probe, which may be hand-held or robotically manipulated.The first set of transducer elements and the second set of transducer elements may comprise a part of the probe, for example mounted within or on the probe.

[0012] The first group of transducer elements and / or the second group of transducer elements may be a linear array of transducer elements, in particular a straight or convex linear array. The first group of transducer elements and / or the second group of transducer elements may be a planar array of transducer elements, in particular a flat or convex planar array. Concave linear or concave planar transducer arrays, or other configurations such as annular arrays may also be used.

[0013] At least one of the first group of transducer elements may also be one of the second group of transducer elements.In fact, the first group of transducer elements may also be, ie comprise, the same transducer elements as the second group of transducer elements.

[0014] For example, if the relative positions of the first and second groups of transducers are known, or if the first and second groups of transducers are identical, the transformation can be obtained directly from the registration process. Alternatively, if the first and second groups of transducers are movable relative to each other, the transformation can also be obtained indirectly from the registration process based on measurements of the relative positions of the two groups of transducer elements.

[0015] The present invention further includes a method for imaging cavitation in an imaging volume of an object. The method may include: generating ultrasound having a focal region; receiving passive detection signals from a first group of transducer elements and generating a cavitation image of cavitation in the focal region based on the passive detection signals; generating reflection imaging ultrasound; receiving reflection imaging detection signals from a second group of transducer elements and generating a reflection image based on the reflection imaging detection signals;

[0016] The reflected image of the imaging volume is registered with the 3D image to obtain a transformation between a coordinate system of the first set of transducer elements and a coordinate system of the 3D image; and the transformation is applied to the cavitation image to align the cavitation image with the 3D image.

[0017] The present invention also provides a device for imaging cavitation in an imaging volume of an object, the device comprising a plurality of transducer elements and a control device, wherein the control device is configured to: control at least a first transducer element to generate focused ultrasound having a focal area; receive passive detection signals from a first group of transducer elements, and generate a cavitation image of the cavitation in the focal area based on the passive detection signals; control at least a second transducer element among the transducer elements to generate reflected imaging ultrasound; receive reflected imaging detection signals from the second group of transducer elements, and generate a reflected anatomical image from the reflected imaging detection signals; and combine the cavitation image and the reflected anatomical image to generate a 3D image of the cavitation in the imaging volume.

[0018] As will now be described, the system may further include any one or more features of the embodiments of the invention shown in the accompanying drawings in any feasible combination. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 is a schematic diagram of an ultrasound system according to an embodiment of the present invention;

[0020] Figure 2 yes Figure 1A schematic diagram of a system for transmitting ultrasound for anatomical imaging;

[0021] Figure 3 yes Figure 1 A schematic diagram of a system for transmitting ultrasound for medical treatment;

[0022] Figure 4 yes Figure 1 A schematic functional block diagram of an ultrasound system;

[0023] Figure 5 is a timing diagram illustrating the operation of a system according to an embodiment of the present invention;

[0024] Figure 6 It is shown in Figure 1 A flowchart of an imaging method performed on a system;

[0025] Figure 7 is a schematic diagram of an ultrasound system according to yet another embodiment of the present invention;

[0026] Figure 8 is a schematic diagram of an external ultrasound probe according to another embodiment of the present invention;

[0027] Fig. 9 is a schematic diagram of an internal ultrasound probe according to yet another embodiment of the present invention; and

[0028] Fig.10 is a schematic diagram of an ultrasound system according to another embodiment of the present invention, the ultrasound system including independent arrays for transmitting and receiving ultrasound waves for ultrasound imaging, transmitting ultrasound waves for therapeutic ultrasound, and receiving passive detection signals for cavitation imaging. DETAILED DESCRIPTION

[0029] refer to Figure 1 , the ultrasound system 200 may include a geometrically focused ultrasound transducer 201, with an array of ultrasound transducer elements 202 located in a hole 203 at the center of the transducer 201. Each transducer element 202 is operable to generate ultrasound and also detect ultrasound. Thus, they may be used in an active mode, in which they generate and detect ultrasound to generate a reflected (e.g., B-mode) ultrasound image, or in a passive mode, in which they only detect ultrasound. The array may be a linear or convex linear array, primarily in Figure 2 The direction shown in will be referred to as the x-direction. The direction along the transducer axis perpendicular to the x-direction will be referred to as the z-direction. Therefore, the imaging plane of the array is the xz plane. The direction perpendicular to both the x- and z-directions will be referred to as the y-direction.

[0030] The control unit 204 is configured to control the generation of ultrasound signals for each transducer element 202 and receive detection signals from each transducer element 202. The control unit 204 may include a preamplifier and filter block 206 and an oscillator 208. The control unit 204 is also configured to control the transducer 201 to control the power and frequency of ultrasound generated by the transducer 201, for example, using a signal from the oscillator 208 to control the frequency of ultrasound. It should be understood that although the control unit 204 is functionally described, the control unit 204 may be composed of a single processor or more than two discrete processors that perform different functions (e.g., control and analysis functions) within the system. The control unit is connected to a display screen 210, and data derived from the detection signal can be displayed on the display screen 210 in a suitable format. In this case, the treatment transducer 201 has a focus in a focal region 214, in which the treatment transducer 201 will generate ultrasound of the highest intensity.

[0031] Although Figure 1 The configuration can be implemented using a variety of components and systems, but in one embodiment, an ultrasound data acquisition system can be used that simultaneously allows raw radio frequency (RF) data or in-phase and quadrature (I / Q) data (which can be demodulated to RF) across a wide ultrasound bandwidth (e.g., 1 to 15 MHz) from multiple individual elements 202. If the array is to be used in a passive mode, pulse transmission can be turned off so that the array only acts to receive. In some modes, one set of transducer elements 202 is used in active mode and another set of transducer elements 202 is used in passive mode, so that active and passive detection can be used simultaneously. In order to make the system clinically applicable, a therapeutic ultrasound transducer transducer 201 can be used, which has a central hole 203 for a linear (straight or convex) detector array 202.

[0032] The theory behind the operation of passive acoustic mapping will now be briefly described, although there is a more detailed description in WO2010 / 052494. Active detection, including pulse echo (e.g., B-mode) imaging, requires an ultrasound generator and a detector or receiver, the ultrasound generator being configured to generate ultrasound typically in pulse form, and the detector or receiver detecting reflected ultrasound or re-emitted ultrasound from the cavitation region, and a processing system, the processing system using the time interval between the generation of ultrasound and the detection of ultrasound to determine the position of the detected cavitation. In contrast, in passive positioning and mapping, there is no direct information about the propagation time from the source to the receiver. Instead, the cross-correlation of the detection signals from a pair of receivers can provide an estimate of the differential arrival time (DTOA), that is, the difference in the arrival time of the signal from the source at the receiver. This enables the distance difference between the receiver and the source to be estimated. By using a set of cross-correlation pairs, single source positioning and extended source mapping are possible. It can be understood from this that a single detector can operate in active detection and passive detection, depending on the processing performed on the sensor signal. Further explanation of passive positioning and imaging is as follows.

[0033] Typically, where there are extended cavitation regions, spatial mapping of the cavitation is necessary. A commonly used approach is a passive beamforming approach, described by Coviello et al., “Passive acoustic mapping utilizing optimal beamforming in ultrasound therapy monitoring,” J. Acoust. Soc. Am, 137(5), May 2015. If a regular pixel grid is defined in the imaging plane in which the spatial mapping is created, each pixel is represented by a 3D coordinate x = [x, y, z] T The center of the bounds is defined, and the spacing in each dimension is [dx,dy,dz] T Given. The equation from pixel position x to position x is defined by j The distance of the receiver j at:

[0034]

[0035] For each pixel, the data at the receiver is pre-controlled and a time delay is applied to each receiver signal to compensate for the propagation time from the imaged pixel to the receiver. If we assume a total of N receivers, the acoustic field intensity at the pixel location is:

[0036]

[0037] Among them, S j(t) is the signal recorded at receiver (sensor) j, τ j (x) = d j (x) / c is the propagation time from position x to sensor j, a is the piezoelectric coefficient that is a characteristic of each receiver (sensor) element, and c is the propagation speed. j The product of (x) compensates for the reduction in source signal intensity caused by the spherical diffusion of the wavefront. An image of the source energy at a pixel is generated by integrating the square of the source intensity over a collection period of length T, assuming uniform detector weighting:

[0038]

[0039] Among them, ρ o is the density of the medium and c is the propagation speed. This energy is then calculated for each desired pixel location in the image.

[0040] Reference Figure 2 and Figure 3 , the control unit 204 can be configured to control the transducer elements 202 as a phased array. For example, the control unit can be configured to generate a transmit signal for each transducer element 202 to control the frequency and timing (i.e., relative phase) of the vibration, thereby controlling the ultrasound generated by each transducer element. Typically, the vibration frequency of each transducer element is controlled to be the same, and the phase or timing of each element is changed in order to manipulate the ultrasound generated by the array as a whole. The transducer elements can be configured to vibrate in phase with each other, which produces ultrasound with straight parallel wavefronts 220 all propagating in the same direction, such as Figure 2 This is suitable for anatomical ultrasound (B-mode or other reflection) imaging. If the vibration phase of the elements 202 is offset so that the vibrations of the elements at the outer ends of the array are in phase with each other and the delay increases towards the center of the array, as shown in FIG. Figure 3 As shown, this then generates ultrasound having a curved wavefront 222 that converges at a focal region 224.

[0041] It should be understood that, unlike having a separate transducer 201 for focused ultrasound transmission, the ultrasound element array 204 can be used to generate ultrasound for both anatomical imaging and therapeutic FUS by rapidly switching between two different phase configurations. In addition, since both the above-mentioned anatomical ultrasound imaging and passive acoustic mapping require detection of ultrasound reflected or generated by the tissue being imaged, in some embodiments of the present invention, this detection can also be accomplished by the same transducer element 202 used to transmit ultrasound. However, this requires further time division, and in many cases, it is preferred to have a separate transducer array to detect or receive ultrasound. Therefore, in the following description involving transmit and receive arrays, these arrays are generally separate arrays, but can also be the same array.

[0042] refer to Figure 4 ,exist Figure 1 In an actual implementation of the system, the transducer elements 202 are divided into two groups, each group of transducer elements is arranged into an array, a transmitting array 202a and a receiving array 202b, and they are all installed in a probe 230, which also includes a position sensor 232. Each of these arrays 202a, 202b can be a linear array as described above. Therefore, the position sensor 232 is omitted. Figure 1 The independent geometric FUS transducer 201 of the embodiment of the present invention is provided in a treatment group and an imaging group. In a modification of this arrangement, transducer elements are provided in a treatment group and an imaging group. The treatment group transducer elements can then be configured to generate focused ultrasound, while the imaging group transducer elements are configured to transmit and receive reflected imaging ultrasound, and receive passive cavitation mapping signals. The imaging group can be configured to transmit flat ultrasound or focused ultrasound, for example, subgroups of transducer elements are controlled to provide different respective focuses at a common focal depth, thereby giving a high quality image at that depth.

[0043] The position sensor may be adapted for use in any of a number of known position and orientation sensing systems. For example, it may be a sensor of an electromagnetic motion tracking system, which may include one or more markers that enable the position of the probe to be tracked with a stereo optical camera, an infrared camera, or a laser tracker.

[0044] The control unit 204 includes a main processor 204a and an ultrasound front-end processor 204b. The ultrasound front-end 204b includes a transmit side and a receive side. On the transmit side, it includes a generator configured to generate each ultrasound signal to be transmitted by the transmit array 202a. For example, these may include a treatment signal generator 240 and an imaging signal generator 242. Each of these signal generators 240, 242 is configured to output a transmit signal to be input to each transducer element of the transmit array 202a, so that they transmit ultrasound signals in the desired form for treatment FUS and for B-mode ultrasound imaging, respectively, such as Figure 2 and Figure 3 As shown. The ultrasound front end 204b further includes two amplifiers 244, 246, each of which is configured to amplify the transmit signal from a corresponding one of the signal generators 240, 242, and a multiplexer 248, which is configured to receive the two amplified transmit signals and send each of them to the correct transmit array 202a in a time-division multiplexed manner at the appropriate time. The timing controller 264 issues a trigger or synchronization signal to arrange the timing of the signal generator and the multiplexer, which will be described in more detail below.

[0045] The receiving side of the ultrasound front end 204b includes a multiplexer 250 that is configured to receive all detection signals from the receive array 202b and separate the anatomical ultrasound imaging signal (e.g., B-mode) from the passive acoustic mapping signal onto the anatomical ultrasound imaging channel and the PAM channel. This separation is based on timing because the received anatomical imaging signal is a reflection of the transmitted anatomical imaging signal and the received PAM signal is generated by the cavitation caused by the transmitted FUS signal. The anatomical imaging signal is time gain compensated by the TGC module 252, digitized by the ADC 254 and filtered by the digital filter 256. The PAM signal is filtered by the analog filter 258 to isolate the high frequency broadband signal for PAM and amplified by the low noise amplifier 260 before being digitized by the ADC 262.

[0046] The main processor 204a includes a timing controller 264 configured to provide timing inputs to the ultrasound signal generators 240, 242, the multiplexers 248, 250, and the ADCs 254, 262. The timing inputs to the ultrasound signal generators 240, 242 are configured to trigger the generation of therapeutic FUS signals and anatomical ultrasound imaging signals in an alternating manner, each signal lasting a corresponding series of brief time periods. The multiplexer 248 uses the timing signals it receives from the timing controller 264 to multiplex the two types of ultrasound generation signals onto the control input of the transmitter array 202a, so that the transmitter array 202a will generate alternating pulses of therapeutic FUS and focused or unfocused imaging ultrasound. The receive multiplexer 250 is controlled by the timing controller 264 to switch the signal from the receive array 202b between the B-mode channel and the PAM channel based on the transmission time of the two different types of ultrasound and the known or assumed delay between the transmission and reception of the relevant ultrasound signal. The timing controller 264 also provides timing inputs to the ADCs 254 , 262 to control the sampling rate of the analog signals by the ADCs.

[0047] See also Figure 5 As an example of different timings for transmitting and receiving ultrasound signals, one may wish to transmit a therapeutic FUS pulse of 1000 cycles with a frequency of 1 MHz every 1 s. One may also wish to maintain a sufficient imaging frame rate (>30 frames / s) until a depth of d=20 cm, but also wish to transmit several pulse-echo imaging pulses to constitute a single image frame to improve the imaging signal-to-noise ratio (assuming 50 pulses / frame). Given a 1 s therapeutic pulse rate, it is necessary to fit all pulse emission times, propagation times, and processing times into this 1 s.

[0048] Example:

[0049] Therapeutic ultrasound frequency = 1MHz,

[0050] Treatment pulse PRF = 1Hz or 1s period,

[0051] The number of cycles of each treatment pulse is N = 1000 cycles.

[0052] Each pulse treatment emission time T trans =1ms,

[0053] Treatment propagation time plus propagation time T trans+prop ~2ms,

[0054] A passive acoustic mapping (PAM) processing time T is added after each pulse. trans+prop+PAM proc =502ms,

[0055] Therefore, the time required to transmit a treatment pulse, detect the cavitation-generated US, and process it into PAM is half of the 1 s period.

[0056] Remaining time = 498ms.

[0057] If the system is synchronous, the remaining time can be used for B-mode imaging. If the system is asynchronous, the B-mode imaging pulse transmission can be immediately after T trans+prop After that. For simplicity, this example only covers the synchronous case.

[0058] Assume that the propagation velocity c = 1500 m / s, and that it takes 10 ms to reconstruct all imaging pulses into an image, and

[0059] Imaging US frequency = 5MHz,

[0060] The number of cycles of each imaging pulse is N = 2 cycles,

[0061] Imaging emission time T trans =0.4μs,

[0062] Add propagation time T trans+prop =26.4μs,

[0063] For each image frame with 50 pulses, T frame =50*26.4μs=1.3ms,

[0064] Plus the image frame reconstruction and processing time:

[0065] T frame +T recon =1.3ms+10ms=11.3ms,

[0066] Frame rate = 498ms / 11.3ms = 44 frames / s. The main processor 204a further includes an apodization unit 266 and an image reconstruction unit 268, which are configured to receive the filtered digital signals from the B-mode channel of the ultrasound front end 204b and generate anatomical ultrasound images therefrom, for example in the form of a 2D B-mode ultrasound imaging stream, which may include a sequence of time-stamped 2D image frames. The main processor 204a further includes a PAM imaging unit 270, which is configured to receive the digital signals from the PAM channel of the ultrasound front end 204b and generate PAM images therefrom, for example in the form of a 2D PAM imaging stream, which may also include a sequence of time-stamped PAM image frames.

[0067] The main processor 204a further includes a positioning unit 272, which is configured to receive position and orientation data (e.g., translation and rotation) from the position sensor 232 on the probe 230, and time stamp the data, and output a position / orientation data stream so that the position and orientation of the probe associated with each form of the image stream can be determined. This allows the probe to be moved to scan the imaging volume, and the 2D images generated from the receiving array of the probe are located in a 3D coordinate system.

[0068] The main processor 204a further includes a local memory 274 and a data processor 276. The local memory 274 is configured to receive and store image streams from the anatomical and PAM imaging channels and a position / orientation data stream from the positioning unit 272. It is also configured to receive and store 3D anatomical image data obtained from a previous scan of the patient, for example in the form of a set of 2D image slices obtained by a CT or MRI scan, which may be in DICOM format, for example. The data processor 276 is configured to process the data stored in the local memory in order to generate a combined image or image stream in which the PAM image of FUS-induced cavitation is superimposed on the 3D anatomical image of the patient, which may be a pre-scanned 3D image, or may be a 3D ultrasound image generated from a combined 2D B-mode ultrasound image slice. A processing method by which the combined image may be obtained will now be described.

[0069] refer to Figure 6, the local memory 274 is also configured to store position system calibration data that defines the position and orientation of a 2D ultrasound imaging plane of a B-mode image generated from the receiver array signals relative to the position and orientation of the probe determined by the position sensor 232. The calibration data may be obtained by imaging a known 3D structure at a known position and orientation relative to the probe 230, and registering the obtained 2D ultrasound image with the image data of the known structure to determine the position and orientation of the imaging plane relative to the probe. The processor 276 is configured at step 300 to apply the calibration defined by the calibration data to the position / orientation data stream to generate image position / orientation data that defines the position and orientation of the imaging plane for each image frame in a 3D coordinate system, which may be referred to as a probe coordinate system.

[0070] Since the PAM images are generated from the same receive array 202b of transducer elements as the 2D anatomical imaging, it can be assumed that the imaging planes of the 2D PAM images and the 2D anatomical images are consistent, and the same coordinate system can be used to determine positions in the imaging planes for both imaging methods. Therefore, the relative positions of the imaging features in the PAM images and the 2D anatomical images are known, and the positions of each type of image are defined and recorded in a common probe coordinate system. However, a further calibration step may be included in which structures where cavitation will occur at known locations are imaged with PAM and 2D reflection (e.g., 2D B-mode) ultrasound imaging, and the relative positions of the imaging planes and positions within these planes are calibrated for the two imaging methods.

[0071] At step 302, the frames of the 2D B-mode image stream and the frames of the 2D PAM image stream are aligned in time with each other. This is usually necessary because the frame rates of the two different imaging methods may be different, and due to the need to multiplex the imaging methods, the timing of the individual frames will not be the same. This temporal alignment together with the position calibration results in defining the position and orientation of each frame in the two image streams and time in the same 4D coordinate system, i.e., 3D spatial coordinate system and time.

[0072] At step 304, the 2D slices of 3D anatomical data are compounded into a 3D image data set for the complete 3D volume of the patient's anatomical structure. Of course, the anatomical data may already be stored in a 3D format, in which case this compounding step is unnecessary. Then at step 306, each 2D ultrasound anatomical image slice is registered with the 3D (typically high contrast) anatomical image. Various methods of registering images are known, such as Wein et al., "Automatic CT-ultrasound registration for diagnostic imaging and image-guided intervention" Medical Image Analysis, Volume 12, pages 577 to 585, 2008. This determines the spatial correction or transformation that can be applied to the coordinates of the 2D anatomical ultrasound images (and PAM images) to correctly position them in the coordinate system of the 3D anatomical image. At step 308, a spatial correction or transformation is applied to the coordinates of the PAM image to determine their position and orientation in the coordinate system of the 3D anatomical image. Therefore, the result of this image registration and coordinate transformation is a 2D anatomical ultrasound image stream defined in the coordinate system of the 3D anatomical image and a 2D PAM image stream defined in the coordinate system of the 3D anatomical image. This allows the 3D high contrast anatomical image and the 2D anatomical ultrasound image and the PAM image to be overlaid in various ways.

[0073] For example, at step 310, a 2D PAM image may be superimposed on a 3D high contrast anatomical image, and then at step 312, the image may be thresholded to identify key sites or reference points of activity, such as points of maximum, minimum or median cavitation. This provides an image of cavitation reference points located in the 3D high contrast anatomical image. Optionally, this image may be combined with a 2D US image stream at step 313 to produce an image including 3D PAM reference points superimposed on a 3D anatomical image, optionally also combined with a 2D reflectance US image.

[0074] Alternatively, at step 314, after overlaying at step 310, the 2D PAM image may be composited to generate a 3D PAM image of cavitation activity located in the 3D anatomical image. The composite 3D image may then also be thresholded at step 316 so that only pixels having a threshold level of cavitation activity or above are shown in the PAM component of the composite image. Optionally, the image may be combined with the 2D US image stream at step 317 to produce an image comprising a 3D PAM image superimposed on the 3D anatomical image, optionally also combined with a 2D reflectance image

[0075] Additionally, the 2D ultrasound image registered with the 3D anatomical image at step 306 may be overlaid with the 3D image at step 319 and displayed as a combined 2D ultrasound and CT or MRI image.

[0076] In another alternative embodiment, for example where a 3D high contrast anatomical image of the patient is not available, the temporally aligned and spatially aligned images from the 2D PAM image stream may be overlaid onto the 2D ultrasound image stream at step 318, thresholded at step 320, and displayed as a combined image showing the 3D PAM key sites superimposed on the 2D ultrasound image, but only when co-located in the 2D US image plane.

[0077] Optionally, the overlapping 2D images obtained at step 318 may be compounded at step 322 to generate a 3D image of cavitation imaged in a PAM image superimposed on the 3D anatomical ultrasound image. The PAM image may be a complete 3D image, or just the reference points as described above.

[0078] In theory, all three image types can be combined to generate an enhanced 3D anatomical image obtained from the 3D anatomical image and multiple anatomical ultrasound 2D images compounded to form a 3D reflection ultrasound image, with the 3D PAM image superimposed on the 2D image. However, such images can be difficult to interpret.

[0079] Of course, it should be understood that Figures 1 to 5 Various modifications can be made to the embodiments shown in . For example, although the transmit and receive arrays 202a, 202b are both 1D linear or convex arrays, one or both of them can be 2D planar arrays. This means that if a full 2D array is used for transmit and receive in anatomical ultrasound imaging, each image frame of the anatomical ultrasound image or ultrasound image stream can be a three-dimensional anatomical image. This also means that if a full 2D receive array is used for PAM imaging, the PAM image can be a full 3D image of the cavitation activity generated by FUS. This also means that a full 2D transmit array can be used to generate FUS.

[0080] refer to Figures 7 to 9 , Figures 2 to 6 The system can be combined in a variety of different probe configurations. For example, refer to Figure 6, the probe 230 may be connected to an electronically or manually controlled motion control system 600, such as a robotic arm or multi-axis motion system, configured to support the probe and control its motion in six degrees of freedom (three along orthogonal translational motion directions and three around orthogonal rotational axes) in response to input from the electronic control system or manual input. In this case, the position and orientation of the probe 230 may be determined by a position sensor 232 mounted on the probe as described above, or may be determined by the operation of the motion control system.

[0081] Reference Figure 8 , the probe may be a handheld external probe 730 having a contact surface 700 configured to contact the patient's skin and having a transmitting array 702a and a receiving array 702b mounted in or near the contact surface 700. In this case, a position sensor 732 is mounted in or fixed to the body of the probe 730 so that all manual movements of the probe can be recorded as described above.

[0082] Reference Fig. 9 , the probe may be a hand-held internal or intraoperative probe 830 having a contact surface 800 configured to contact the interior of a patient and having a transmit array 802a and a receive array 802b mounted in or near the contact surface 800. In this case, a position sensor 832 is again mounted in the body of the probe 830 so that all manual movements of the probe can be recorded as described above.

[0083] refer to Fig.10 Instead of all being mounted on a common probe, the system may include separate probes, each supporting a different set of transducer elements. For example, the system may include an anatomical imaging probe 900, on which an array 902 of transducer elements is supported. The array 902 may be a linear or convex array, and may be configured to transmit reflected imaging ultrasound, such as Figure 2 , and receiving reflected ultrasound, either using the same set of transducer elements within array 902, or using different sets of transducer elements within array 902, or using separate transducer element arrays. The system may include a FUS probe 904 having an array of transducer elements 906 configured, for example, as Figure 3The therapeutic FUS is generated as shown. The system may further include a PAM probe 908 having an array of transducer elements 910 configured to receive. Each of the probes 900, 904, 908 further includes a position sensor 912, 914, 916 so that the position of the probe and therefore the transducer array mounted on the probe can be monitored. The system can then operate in the same manner as the above-described system, except that the calibration step 300 for spatially aligning the PAM image with the anatomical ultrasound image is replaced by a transformation that varies over time and is determined for each image frame of the PAM image stream based on the relative position of the two probes 900, 908.

[0084] In another embodiment, the system includes a FUS ultrasound transmitter mounted on a probe or a robotic arm, and a movable probe having PAM imaging receiving transducer elements and transmitting elements and receiving elements of an anatomical ultrasound imaging system on the probe, either as independent arrays, or as a single common array, or as a transmitting array for anatomical ultrasound imaging and a receiving array for PAM imaging and anatomical ultrasound imaging.

Claims

1. A device for imaging cavitation in an object volume of an object, the device comprising a plurality of transducer elements and a control device, wherein: The control device is configured to: controlling at least a first one of the transducer elements to generate ultrasound having a focal region; receiving passive detection signals from a first set of transducer elements and generating a cavitation image of the cavitation in the focal region based on the passive detection signals; controlling at least a second one of the transducer elements to generate reflection imaging ultrasound; receiving a reflection imaging detection signal from a second group of transducer elements, and generating a reflection image based on the reflection imaging detection signal; registering the reflected image with the 3D image of the object volume to obtain a transformation between a coordinate system of the first set of transducer elements and a coordinate system of the 3D image; as well as The transformation is applied to the cavitation image to align the cavitation image with the 3D image.

2. The device according to claim 1, wherein The first group of transducer elements is in a fixed position relative to the second group of transducer elements.

3. The device according to claim 1 or 2, further comprising a probe, wherein: The first group of transducer elements and the second group of transducer elements are mounted on the probe.

4. The device according to claim 1 or 2, wherein: The first set of transducer elements is a straight or convex linear array of transducer elements.

5. The device according to claim 1 or 2, wherein: The second set of transducer elements is a straight or convex linear array of transducer elements.

6. The device according to claim 1 or 2, wherein: At least one of the first set of transducer elements is also one of the second set of transducer elements.

7. The device according to claim 6, wherein: The first set of transducer elements is also the second set of transducer elements.

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