This invention relates to medical diagnostic ultrasound systems and, in particular, to ultrasound systems which perform imaging and therapy by sonothrombolysis.
Ischemic stroke is one of the most debilitating disorders known to medicine. The blockage of the flow of blood to the brain can rapidly result in paralysis or death. Attempts to achieve recanalization through thrombolytic drug therapy such as treatment with tissue plasminogen activator (tPA) has been reported to cause symptomatic intracerebral hemorrhage in a number of cases. Advances in the diagnosis and treatment of this crippling affliction are the subject of continuing medical research.
International patent publication WO 2008/017997 (Browning et al.) describes an ultrasound system which provides microbubble-mediated therapy to a thrombus such as one causing ischemic stroke. Microbubbles are infused, delivered in a bolus injection, or developed into the bloodstream and flow to the vicinity of a thrombus. Ultrasound energy is delivered to the microbubbles at the thrombus to disrupt or rupture the microbubbles. This microbubble activity can in many instances aid in dissolving or breaking up the blood clot and return a nourishing flow of blood to the brain and other organs. Such microbubble activity can be used to deliver drugs encapsulated in microbubble shells, and well as microbubble-mediated sonothrombolysis.
The Browning et al. publication shows the ultrasonic energy being delivered for sonothrombolysis from an ultrasound array probe controlled by an ultrasound system. For sonothrombolysis treatments to be clinically safe and effective, the ultrasound array probe delivering the ultrasound energy to the clot target region should meet various requirements. First, the probe must be capable of adequate ultrasound energy delivery at the clot site, sufficient to stimulate sonothrombolytic activity in arteries within the brain. Second, the energy delivery should be directionally controllable, providing the capability to target the tissue surrounding the clot. The energy delivered should be controllable, providing the ability to reach both deep and shallow clots. The array should be sized and shaped to fit an acoustic window of the skull, and preferably have the ability to indicate correct placement on the patient's temporal bone window. Finally, the system should provide the capability to estimate the in-situ pressure for proper ultrasound dose delivery and enhanced treatment safety.
In accordance with the principles of the present invention, a transducer array and ultrasound system are described which provide the ability to perform sonothrombolytic treatment using a standard 128-channel beamformer. The transducer array in the probe is a two dimensional array so that the energy delivery can be controllably directed in three dimensions. The array is generally rounded and shaped to fit the temporal bone window of a patient's head. Exemplary transducer arrays are described which can be powered by a standard system beamformer, capable of delivering sufficient energy to stimulate sonothrombolysis. Implementations are described with imaging transducer elements that are, in combination with the ultrasound systems, optimized for functionality other than therapeutic energy delivery, such as A-line imaging, Doppler detection, skull thickness ranging, or sensitivity to signals characteristic of cavitation.
In the drawings:
In some aspects, the present invention includes an ultrasonic therapy system comprising instructions thereon that when executed cause the system to transmit therapeutic ultrasound energy from a two dimensional array of therapy transducer elements toward an occlusion in a cranial vascular system, and transmit other than therapeutic ultrasound energy from imaging transducer elements positioned with the two dimensional array of therapy transducer elements. The two dimensional array can include rectilinearly diced transducer elements arranged in a pattern with corner elements missing to provide a generally rounded array shape.
In certain aspects, a number of therapy transducer elements in the two dimensional array is 128, and the ultrasonic therapy system further includes a 128-channel beamformer. The imaging transducer elements can be centrally positioned in the two dimensional array of therapy ultrasound elements. In some aspects, the imaging transducer elements are peripherally positioned around the two dimensional array of therapy transducer elements. The number of imaging elements can range, and can be generally less than the number of therapy transducer elements. For example, a number of the imaging transducer elements is four. In some aspects, twenty imaging transducer elements arranged in groups of five elements, each group being located on a side of the two dimensional array of therapy transducer elements In certain aspects, the imaging transducer elements (e.g., four elements) can be coupled together for operation in parallel as a transducer patch. In certain aspects, the imaging transducer elements can be peripherally positioned around the two dimensional array of therapy transducer elements, and, alternatively, the imaging transducer elements are coupled together for operation in parallel.
In certain aspects, the system can include instructions that when executed cause the imaging transducer elements to transmit ultrasound at a higher frequency than the therapy transducer elements, and/or the imaging transducer elements can be structurally configured to operate at a higher frequency than the therapy transducer elements. For example, the imaging transducer elements can include a smaller height than the therapy transducer elements. In some aspects, the imaging transducer elements can also include a heavier backing for wider bandwidth and/or a different acoustic matching layer for different energy coupling into a body. As described further herein, the imaging transducer elements and the ultrasound system can be configured for one of A-line imaging, Doppler detection, or skull thickness ranging. The imaging transducer elements can also have a bandwidth sensitive to sub- or ultraharmonic frequencies characteristic of cavitation. In certain aspects, the ultrasonic therapy system can include a cavitation detector, responsive to signals produced by the imaging transducer elements, and amplifier electronics that are coupled to the two dimensional array and configured to control the ultrasonic energy produced by the therapy transducer elements.
Referring to
The echo signals received by elements of the array 10 are coupled to the system beamformer 20 where the signals are combined into coherent beamformed signals. For example, the system beamformer 20 in this example has 128 channels, each of which drives an element of the array to transmit energy for therapy or imaging, and receives echo signals from one of the transducer elements. In this way the array is controlled to transmit steered beams of energy and to steer and focus received beams of echo signals.
The beamformed receive signals are coupled to a fundamental/harmonic signal separator 22. The separator 22 acts to separate linear and nonlinear signals so as to enable the identification of the strongly nonlinear echo signals returned from microbubbles or tissue. The separator 22 may operate in a variety of ways such as by bandpass filtering the received signals in fundamental frequency and harmonic frequency bands (including super-,sub-, and/or ultra-harmonic signal bands), or by a process for fundamental frequency cancellation such as pulse inversion or amplitude modulated harmonic separation. Other pulse sequences with various amplitudes and pulse lengths may also be used for both linear signal suppression and nonlinear signal enhancement. A suitable fundamental/harmonic signal separator is shown and described in international patent publication WO 2005/074805 (Bruce et al.) The separated signals are coupled to a signal processor 24 where they may undergo additional enhancement such as speckle removal, signal compounding, and noise elimination.
The processed signals are coupled to a B mode processor 26 and a cavitation processor 28. The B mode processor 26 employs amplitude detection for the imaging of structures in the body such as muscle, tissue, and blood cells. B mode images of structure of the body may be formed in either the harmonic mode or the fundamental mode. Tissues in the body and microbubbles both return both types of signals and the stronger harmonic returns of microbubbles enable microbubbles to be clearly segmented in an image in most applications. A cavitation processor 28 detects signal characteristics of cavitation and produces cavitation image and alert signals as described below. The system may also include a Doppler processor which processes temporally distinct signals from tissue and blood flow for the detection of motion of substances in the image field including red blood cells and microbubbles. The anatomic and cavitation signals produced by these processors are coupled to a scan converter 32 and a volume renderer 34, which produce image data of tissue structure, flow, cavitation, or a combined image of several of these characteristics. The scan converter converts echo signals with polar coordinates into image signals of the desired image format such as a sector image in Cartesian coordinates. The volume renderer 34 converts a 3D data set into a projected 3D image as viewed from a given reference point as described in U.S. Pat. No. 6,530,885 (Entrekin et al.) As described therein, when the reference point of the rendering is changed the 3D image can appear to rotate in what is known as kinetic parallax. This image manipulation is controlled by the user as indicated by the Display Control line between the user interface 38 and the volume renderer 34. Also described is the representation of a 3D volume by planar images of different image planes, a technique known as multiplanar reformatting. The volume renderer 34 can operate on image data in either rectilinear or polar coordinates as described in U.S. Pat. No. 6,723,050 (Dow et al.) The 2D or 3D images are coupled from the scan converter and volume renderer to an image processor 30 for further enhancement, buffering and temporary storage for display on an image display 40.
A graphics processor 36 is also coupled to the image processor 30 which generates graphic overlays for displaying with the ultrasound images. These graphic overlays can contain standard identifying information such as patient name, date and time of the image, imaging parameters, and the like, and can also produce a graphic overlay of a beam vector steered by the user as described below. For this purpose the graphics processor received input from the user interface 38. In an embodiment of the present invention the graphics processor can be used to overlay a cavitation image over a corresponding anatomical B mode image. The user interface is also coupled to the transmit controller 18 to control the generation of ultrasound signals from the transducer array 10 and hence the images produced by and therapy applied by the transducer array. The transmit parameters controlled in response to user adjustment include the MI (Mechanical Index) which controls the peak intensity of the transmitted waves, which is related to cavitational effects of the ultrasound, and steering of the transmitted beams for image positioning and/or positioning (steering) of a therapy beam as discussed below.
When the site of the treatment such as a thrombus 144 is being imaged in the volume 102, a microbubble contrast agent is introduced into the patient's bloodstream. In a short time the microbubbles in the bloodstream will flow to the vasculature of the treatment site and appear in the 3D image. Therapy can then be applied by agitating or breaking microbubbles at the site of the stenosis in an effort to dissolve the blood clot. The clinician activates the “therapy” mode, and a therapy graphic 110 appears in the image field 102, depicting the vector path of a therapeutic ultrasound beam with a graphic thereon which may be set to the depth of the thrombus. The therapeutic ultrasound beam is manipulated by a control on the user interface 38 until the vector graphic 110 is focused at the site of the blockage. The energy produced for the therapeutic beam can be within the energy limits of diagnostic ultrasound or in excess of the ultrasound levels permitted for diagnostic ultrasound. The energy of the resulting microbubble ruptures will strongly agitate a blood clot, tending to lyse the clot and dissolve it in the bloodstream. In many instances insonification of the microbubbles at diagnostic energy levels will be sufficient to dissolve the clot. Rather than breaking in a single event, the microbubbles may be vibrated and oscillated, and the energy from such extended oscillation prior to dissolution of the microbubbles can be sufficient to lyse the clot.
Existing transcranial probes are designed for imaging and flow diagnostic purposes. As such, these probes tend to be higher-frequency (center frequency generally in the range of 1.6 to 2.5 MHz) probes, utilizing wide bandwidth piezoelectric transducer elements meeting the λ/2 size requirement. These probes generate reasonable ultrasound images of the brain and its vasculature, but at a cost of penetration depth, efficiency, and output power. Furthermore, most of these probes are also not specifically designed to be used transcranially, thus not taking advantage of the full (either mostly circular or ellipsoidal) aperture (typically 2-2.5 cm) that the temporal bone window provides, resulting in further reduced output power due to a smaller probe aperture. In accordance with the principles of the present invention, the array transducer 10 is formed as a generally rounded array 10 of 128 therapy elements 70 as shown in
A basic array 10 of the present invention is shown in
In the manufacture of a transducer array of the present invention, a 2D ultrasound array is fabricated in the usual manner (e.g., lapping, dicing, etc.) with the characteristics of each of the elements fine-tuned for the sonothrombolysis therapeutic application, e.g., 1 MHz, 2-6 cm depth focusing, +/−27o off-axis steering capability, narrow bandwidth, high efficiency, high output power, circular aperture. A subset of the elements of the array is set aside and fine-tuned so their electrical and acoustic characteristics match a special application, e.g., 1.6-2.0 MHz, wide bandwidth, high sensitivity for A-line imaging, Doppler detection, or skull thickness ranging. Alternatively, the electrical and acoustic characteristics of the subset of elements are fine-tuned to be sensitive to sub- or ultraharmonic frequencies of the main therapeutic frequency to enable better detection of these frequencies for implementing a passive cavitation detection functionality. The specialized elements are combined electrically or acoustically to form an element patch which, while narrowing their directivity, increases their sensitivity to the desired signals.
In use, the therapeutic elements are powered to deliver the sonothrombolysis therapy, focusing the array on the clot target and surrounding tissue. The subset of specialized elements is used to
a. Gauge the quality of the temporal bone window by examining the amplitude of the echo reflected from the contralateral side of the skull. A larger amplitude implies a thinner temporal bone window, and/or a better position for the entire array on the temporal bone window.
b. Determine the flow and/or absence of flow of the middle-cerebral artery by operating the patch in Doppler mode, to help in targeting the sonothrombolysis beam to the occlusion.
c. Determine the thickness of the temporal bone window directly by use of a high-frequency patch, e.g., 10-20 MHz. This information is used to modulate the output power of the sonothrombolysis therapeutic array: a thinner temporal bone window would require a lower sonothrombolysis output pressure in order to achieve the same in-situ pressure as compared to a thicker temporal bone window. Or,
d. Determine the in-situ pressure by listening to the signal emanating from the microbubbles while being subjected to the sonothrombolysis treatment frequency, via detection/classification of the spectrum of the returning signal by the cavitation processor 28. If the signature for inertial cavitation is detected, for example, and stable cavitation is desired, the inertial cavitation detector 50 produces an alarm by a speaker 42. The user responds to this information by reducing the ultrasound output power (MI) being generated by the sonothrombolysis array. If cavitation is not detected at all, for example, by no indication of cavitation coloring of the site of the occlusion in the image by the cavitation processor 28, then the output power of the sonothrombolysis array is increased until cavitation is detected. This output power scaling can also be accomplished automatically without user intervention via an output power control loop, for example. The treatment is continued at this setting. Such usage allows the system to compensate for the attenuation generated by different temporal bone windows and any varying attenuation due to different acoustic properties of brain tissue.
The transducer array of
The concepts of the present invention can be extended to patches consisting of more or less than four elements and overall matrix array geometries with more than 128 elements. Geometries such as that shown in
It should be noted that the various embodiments described above and illustrated by drawings may be implemented in hardware, software or a combination thereof. The various embodiments and/or components, for example, the modules, or components and controllers therein, also may be implemented as part of one or more computers or microprocessors. The computer or processor may include a computing device, an input device, a display unit and an interface, for example, for accessing the Internet. The computer or processor may include a microprocessor. The microprocessor may be connected to a communication bus, for example, to access a PACS system. The computer or processor may also include a memory. The memory may include Random Access Memory (RAM) and Read Only Memory (ROM). The computer or processor further may include a storage device, which may be a hard disk drive or a removable storage drive such as a floppy disk drive, optical disk drive, solid-state thumb drive, and the like. The storage device may also be other similar means for loading computer programs or other instructions into the computer or processor.
As used herein, the term “computer” or “module” or “processor” may include any processor-based or microprocessor-based system including systems using microcontrollers, reduced instruction set computers (RISC), ASICs, logic circuits, and any other circuit or processor capable of executing the functions described herein. The above examples are exemplary only, and are thus not intended to limit in any way the definition and/or meaning of these terms. The computer or processor executes a set of instructions that are stored in one or more storage elements, in order to process input data. The storage elements may also store data or other information as desired or needed. The storage element may be in the form of an information source or a physical memory element within a processing machine.
The set of instructions may include various commands that instruct the computer or processor as a processing machine to perform specific operations such as the methods and processes of the various embodiments of the invention. The set of instructions may be in the form of a software program. The software may be in various forms such as system software or application software and which may be embodied as a tangible and non-transitory computer readable medium. Further, the software may be in the form of a collection of separate programs or modules, a program module within a larger program or a portion of a program module. The software also may include modular programming in the form of object-oriented programming. The processing of input data by the processing machine may be in response to operator commands, or in response to results of previous processing, or in response to a request made by another processing machine.
Furthermore, the limitations of the following claims are not written in means-plus-function format and are not intended to be interpreted based on 35 U.S.C. 112, sixth paragraph, unless and until such claim limitations expressly use the phrase “means for” followed by a statement of function devoid of further structure.
This application claims priority to U.S. Prov. Appl. No. 62/140,018, filed on Mar. 30, 2015, which is incorporated by reference herein in its entirety.
Filing Document | Filing Date | Country | Kind |
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PCT/IB2016/051758 | 3/29/2016 | WO | 00 |
Number | Date | Country | |
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62140018 | Mar 2015 | US |