ULTRASONIC SONOTHROMBOLYSIS TREATMENT PLANNING
1. An ultrasound system adapted to perform therapy on a subject comprising:
- an array of transducer elements, configured to transmit a plurality of therapeutic ultrasonic energy beams aimed at a therapeutic site;
a diagnostic imaging modality which is adapted to produce a vascular map of the therapeutic site, the vascular map comprising a volume rendering of flow signals acquired at the therapeutic site;
a therapy beam transmit controller, responsive to a treatment plan formulated in consideration of the flow signals, which is adapted to transmit a variable sequence of differently steered therapy beams to the therapeutic site during a plurality of transmission intervals.
An ultrasound system utilizes an array transducer to perform sonothrombolysis treatment. The system also produces a vascular map of flow characteristics in the vicinity of the therapy site in a subject. The vascular map is used to formulate a treatment plan which includes the number, focusing, timing, and steering of beams of a pattern of therapy beams transmitted during a transmission interval. Formulation of the treatment plan considers factors such as the direction of microbubble flow toward a therapy site, the flow velocity, the spacing between successive therapy beam transmissions, the number of therapy beams needed to “paint” a therapy region, and grating lobe locations, many of which can be determined from the vascular map.
- 1. An ultrasound system adapted to perform therapy on a subject comprising:
an array of transducer elements, configured to transmit a plurality of therapeutic ultrasonic energy beams aimed at a therapeutic site; a diagnostic imaging modality which is adapted to produce a vascular map of the therapeutic site, the vascular map comprising a volume rendering of flow signals acquired at the therapeutic site; a therapy beam transmit controller, responsive to a treatment plan formulated in consideration of the flow signals, which is adapted to transmit a variable sequence of differently steered therapy beams to the therapeutic site during a plurality of transmission intervals.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
This application claims the benefit of and priority to U.S. 62/430,963, filed Dec. 7, 2016, which is incorporated by reference in its entirety.
This invention relates to medical 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.
U.S. Pat. No. 8,211,023 (Swan et al.) describes an ultrasound system which provides microbubble-mediated therapy to a thrombus such as one causing ischemic stroke, a procedure referred to as sonothrombolysis. Microbubbles are infused, delivered in a bolus injection, or developed in the bloodstream and flow to the vicinity of a thrombus. Ultrasound energy is delivered to the microbubbles at the site of the thrombus to disrupt or rupture the microbubbles. This energetic microbubble activity can in many instances aid in dissolving or breaking up the blood clot and returning 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 Swan et al. patent shows the ultrasonic energy being delivered for sonothrombolysis by an ultrasound beam aimed at a blood clot from an ultrasound array probe controlled by an ultrasound system, e.g. via a single beam in a signal direction.
The present invention recognizes sonothrombolysis therapies (and other therapies utilizing ultrasound disruption of microbubbles or other vascular resonators) that involve merely targeting the treatment locale are often inefficient due to premature oscillation and destruction of microbubbles or other vascular resonators near or at the treatment site. For example, grating lobes from the ultrasound beam can cause enough pressure to lyse the microbubbles and reduce their quantity to a level which is not effective to disrupt a vessel occlusion. This often leads to longer treatment times (requiring multiple applications of microbubble delivery and sonication) and/or ineffective therapy.
The present invention solves these problem with an automated treatment plan that tailors timing and positioning of therapeutic ultrasound beams based on several vasculature parameters (e.g., vessel locale, locale of treatment site or clot in the vessel, blood flow direction) and vascular resonator disruption. This enables focused application of acoustic beams to a treatment zone at a time and position when microbubble disruption would be most effective. This invention enables a desired amount of acoustic therapy to be applied to a specific tissue target, in the presence of channels of flowing blood containing vascular resonators.
It is an object of the present invention to plan a sonothrombolysis procedure, including the location and timing of the beam pattern delivering the ultrasonic energy, in consideration of the physiological makeup of a thrombus and the physiology of the subject.
It is a further object of the present invention to plan a sonothrombolysis procedure from an understanding of the vasculature surrounding a thrombus and which delivers the flow of vascular resonators (e.g., gas-filled microbubbles, drug-filled microbubbles, phase-shift emulsions and polymeric cups) necessary for the procedure to the treatment site. While the description often refers to disruption of microbubbles, it is understood that the objects and principles described herein can be applied to any vascular resonator.
In accordance with the principles of the present invention, an ultrasound system is described which performs therapeutic ultrasound treatment using diagnostic imaging to generate a vascular map of the vasculature delivering a flow of vascular resonators to the site of a procedure. The vascular map reveals the topography of resonator flow, which guides the planning of the targeting of the therapy beam pattern in both timing and location. The resulting therapy plan is formulated in consideration of factors such as the direction of resonator flow toward a therapy site, the flow velocity, the spacing between successive therapy beam transmissions, the number of therapy beams needed to “paint” a therapy region, and grating lobe locations, many of which can be determined from the vascular map. The treatment procedure then proceeds in accordance with the planned therapy beam control which is executed by the system transmit controller, subject to updating as dictated by the progress of the procedure.
While the detailed description below specifies use of vascular mapping for sonothrombolysis ultrasound therapy, it is understood that the present invention enables focused application of acoustic therapy for targeted vascular resonator disruption that yields improved and efficient therapeutic results in a wide variety of therapeutic treatments. As such, the present invention is applicable to any application that relies on sonification of microbubbles or other vascular resonators in the vasculature to yield a therapeutic effect. For example, systems and methods described herein would also be relevant to technologies that use vascular resonators to elicit blood brain barrier disruption, sensitization of tissues to drug delivery (e.g. chemotherapy, stem cells, nanotherapeutics, antibodies, viruses, nuclear material, biomolecules, vasoactive compounds), or tissue ablation.
In the drawings:
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 aimed and focused at specific target locations in the body 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 and, for the present invention, fundamental frequency signals for detection of probe movement. 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 separation 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 fundamental and/or nonlinear (harmonic) 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 Doppler 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. This characteristic is useful when forming a vascular map of the flow of microbubbles in vessels in the body. The Doppler processor 28 processes temporally distinct signals from tissue and blood flow by fast Fourier transformation (FFT) or other Doppler detection techniques for the detection of motion of substances in the image field including blood cells and microbubbles. The Doppler processor may also include a wall filter to eliminate unwanted strong signal returns from tissue in the vicinity of flow such as vessel walls. The anatomic and Doppler flow 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, or a combined image of both 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 or pattern of transmit beams controllably steered by the user as described below. For this purpose the graphics processor receives input from the user interface 38. In the embodiment of
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 on the display, depicting the vector path of a therapeutic ultrasound beam with a graphic thereon which may be aimed at a blood clot. The therapeutic ultrasound beam is manipulated by a control on the user interface 38 until the tip of the vector graphic 110 and consequently the ultrasound beam 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 microbubbles in a single rupture 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. When vigorous activity of the microbubbles is desired to quickly lyse a blood clot or rapidly break up a large clot, it may be decided to induce cavitation at the site of the blockage to stimulate this activity. Inertial cavitation will produce the most vigorous activity, while stable cavitation will produce a lower level of microbubble agitation. The presence of cavitation at the site of the occlusion and its type is detected by a cavitation detector 50, which analyzes characteristics of r.f. echo signals to determine whether cavitation is occurring and, if so, the type of cavitation. The two different forms of cavitation produce ultrasonic backscatter of different characteristics. Stable cavitation produces a strong subharmonic response, while unstable, or inertial cavitation produces broadband noise. The cavitation detector analyzes returning echo signals, e.g., by spectral analysis, for indications of these characteristics and informs the clinician when cavitation is identified, for example by coloring the site of the therapy in an ultrasound image with a color where cavitation has been identified. If the signature for inertial cavitation is detected, for example, and stable cavitation is desired, the inertial cavitation detector 50 causes speaker 42 to issue an alarm. 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, then the output power of the sonothrombolysis array is increased until cavitation is detected. Typical in situ acoustic pressures used to elicit the desired microbubble activity are generally in the range of 200 kPa to 400 kPa. This output power scaling can be accomplished automatically without user intervention via an output power control loop, for instance. The treatment is continued at the appropriate 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.
In accordance with the principles of the present invention, a map is produced for display to the user of the vascular flow surrounding the thrombus 144 in the volumetric region 102. Any diagnostic imaging modality, such as a CT (computed tomography), CTA (computed tomography angiography), angiography, magnetic resonance imaging, or ultrasound imaging can be used to generate the vascular map in accordance with the invention.
In certain embodiments, low MI (non-destructive) ultrasound can also be used, and the echo returns monitored and/or recorded to track the vascular resonator flow over a plurality of imaging frames.
In some embodiments, ultrasound imaging can be used to generate a vascular map. The ultrasound probe used to generate the vascular map may be the same probe or different probe from the probe used for thrombolysis. In such embodiments, Doppler processing may be used. The Doppler processing can comprise power Doppler processing, in which the magnitudes of the flow signals at points inside the volume are estimated and displayed in a volume rendering in colors depicting the magnitudes of the flow signals. A 3D image is normally displayed in overlay with a B mode image of the vessel tissue so that the flow is shown inside the vessels carrying the flow. But in a 3D rendering the tissue will obscure much of the flow behind the outer surface of the volume, and so a preferred display technique is to display the flow alone, so that only the paths of the microbubble and blood flow are displayed, as described in U.S. Pat. No. 5,474,073 (Schwartz et al.) In a preferred implementation of the present invention, the Doppler processing used is colorflow Doppler, in which flow signals above a noise threshold are displayed in colors depicting the direction of flow at each point in a vessel, and color shading depicting the flow velocity. The resulting rendered 3D image, again displayed without the usual B mode tissue overlay, is a map appearing as a 3D web of flow paths of the cranial vasculature, with colors indicating the velocity and direction of flow in the vessels. The production of such a colorflow Doppler vascular map is described and illustrated in U.S. Pat. No. 6,682,483 (Abend et al.), for example. Such a 3D map of the flow around a thrombus will indicate the location of microbubbles in the vessel where the thrombus is lodged and, importantly for an implementation of the present invention, the flow and speed of flow of microbubbles toward thrombus, that is, the flow paths which are supplying fresh microbubbles to the therapy site.
In accordance with the principles of the present invention, the flow characteristics which conduct fresh microbubbles to the site of the thrombus, such as the speed and direction of the flow, information which is present in the vascular map of the blood and microbubble flow, are used to plan the pattern of therapy beams used to lyse a thrombus.
The therapy beam sequence of
Other factors revealed by the vascular flow map may also be taken into consideration when planning the sonothrombolysis therapy. For instance, the presence of grating lobes that undesirably disrupt microbubbles at target sites to which therapy beams have not yet been directed in a sequence can also be considered, as explained in conjunction with
The starting point for development of a treatment plan is generally a default treatment plan which has been predetermined and stored in memory in the ultrasound system. A default treatment plan is one which is composed of a large number of individual treatment sites such as that shown in
Starting from this default treatment plan and its beam pattern, the microbubble flow direction and vessel topography revealed by the vascular flow map indicate that a more effective treatment plan can be developed by considering these factors. One such treatment plan beam sequence is shown in
In a constructed implementation of the present invention, the formulation of the treatment plan and its therapeutic beam sequencing can be done manually by a clinician, or automatically by a therapy planning program or module of the ultrasound system which is programmed to do so. For instance, the clinician can aim the therapeutic beam vector 142, 110 at the thrombus to set the depth and location of the beam pattern transmitted under control of the transmit controller 18. Then the clinician can call up an image of the default treatment plan and, by observing flow characteristics in the vascular map such as the direction of microbubble flow to the thrombus, set the sequence in which selected beams are to be transmitted as illustrated in
It should be noted that an ultrasound system suitable for use in an implementation of the present invention, and in particular the component structure of the ultrasound system described in
As used herein, the term “computer” or “module” or “processor” or “workstation” 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 of an ultrasound system including those controlling the acquisition, processing, and transmission of ultrasound images as described above may include various commands that instruct a 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. For instance, the ultrasound system of
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.