Multi-faceted movement management system

Abstract

A multiplanar motion management system to assist in the administration of non-invasive radiation therapy. The disclosed devices and techniques allow the clinician to accurately monitor the position and motion of the heart with respect to the reference situation of the simulation phase. In addition, information is provided about possible drifts of the patient's respiratory phase and anatomical structures. This information can be used by the clinician to manually interrupt the radiation therapy if necessary. The information can also be used to automatically and in real time provide appropriate gating signals to the treatment machine. The disclosed system can be configured to cover all motion aspects required during a typical radiation therapy workflow, from patient set-up (inter-treatment motion monitoring) to cardiac and respiratory motion monitoring during treatment (intra-treatment motion monitoring) with only one device.

Description

[Technical field]

[0001] The present disclosure relates generally to devices and techniques for external beam therapy, and more particularly to the non-invasive treatment of cardiac arrhythmias.

[0002] Related Applications This patent application claims the benefit of U.S. Provisional Patent Application No. 63 / 129,694, filed December 23, 2020, the disclosure of which is incorporated by reference in its entirety. [Background technology]

[0003] Cardiac arrhythmias are disruptions to the normal heartbeat. They affect more than 2 percent of the general European population and are expected to at least double in the next 50 years as the population ages. The occurrence of cardiac arrhythmias is strongly associated with an increased risk of heart attacks and strokes.

[0004] More specifically, cardiac arrhythmia is a problem with the rate or rhythm of the heartbeat. The heart beats too fast, too slow, or in an irregular pattern. A heart rate faster than normal at rest, more than 100 beats per minute in an adult, is called tachycardia. A heart rate that is too slow, less than 60 beats per minute, is called bradycardia. A common type of cardiac arrhythmia is atrial fibrillation, which causes an irregular and fast heartbeat. Many factors can affect the heart rhythm, such as having a heart attack, smoking, congenital heart disease, and stress. Some substances or drugs can also cause cardiac arrhythmia.

[0005] Treatment may include medications, ablation therapy, or medical procedures such as implantation of a pacemaker or defibrillator and surgery. Medications for fast heart rates may include drugs such as beta blockers or procainamide that attempt to restore normal heart rhythm. Medication may have more serious side effects, especially if taken over a long period of time. Pacemakers are often used for slow heart rates. People with irregular heart rates are often treated with anticoagulants to lower the risk of complications. People with serious symptoms from cardiac arrhythmias may receive emergency treatment with controlled electrical shock in the form of cardioversion or defibrillation.

[0006] Ablation therapy is often used to treat cardiac arrhythmias. Ablation therapy involves burning or freezing specific cardiac tissues with an invasive instrument, such as a catheter, to stop the conduction of disturbed electrical signals in these specific tissues. Invasive catheter ablation procedures are manually performed surgical interventions with highly variable cure rates, ranging from 50% to 80%, depending on the technique used and the skill of the surgeon. Furthermore, the procedure may involve several medical staff members and may take a long time, during which the patient is exposed to the risk of serious complications such as tissue perforation, venous stenosis, or thrombus formation. The nature of the injuries caused by catheter ablation leads to procedures that are often repeated over successive periods of time, increasing the complexity for the medical staff and the risk to the patient. Summary of the Invention [Problem to be solved by the invention]

[0007] Therefore, there is a need for a method of treatment using a non-invasive device that treats cardiac arrhythmias via non-invasive ablation. The use of external treatment beams, including but not limited to charged particle beams, photon beams, proton beams, and carbon and helium ions, provides a non-invasive technique for cardiac ablation. Improvements in devices and methods for such external beam treatments that take into account the real-world motion of the patient's body would be welcome. [Means for solving the problem]

[0008] Various embodiments of the present disclosure allow for accurate patient setup and beam delivery for an external treatment beam based on the position of the patient's heart. This may be beneficial not only for patients with cardiac disease, but also for example, lung cancer patients undergoing radiation therapy, where the heart may be an organ at risk to be tracked during treatment. The disclosed devices and techniques are an extension of International Patent Application PCT / US2020 / 060054, entitled "Cardiac Phase Gating System for Radiation Therapy," filed on November 11, 2020, and issued to Garonna et al. and owned by the present owner. The present disclosure extends from Gronna et al. by providing an improved method for identifying respiratory motion phases and locating absolute heart position in a known coordinate system in three-dimensional space. Various embodiments of the present disclosure track the heart to identify target motion phases and positions without segmentation of any anatomical landmarks (or fiducials) in the image. Such techniques also do not require co-registration or fusion of MRI or CT images with ultrasound, thereby avoiding the inaccuracies and run-time requirements associated with registration across different modalities. Thus, the devices and techniques disclosed herein are advantageous in that image processing and motion measurement are fully automated (no operator or clinician intervention), reproducible, and faster than conventional motion control systems.

[0009] In some embodiments, the external motion of the patient's chest detected using the surrogate is combined with the internal motion of the heart detected by a multiplanar probe generating multiplanar (non-parallel) images to better understand how the heart moves due to respiratory motion. The combination of external and internal motion detection allows for the extraction of respiratory motion patterns from images of the heart. The disclosed devices and techniques are further capable of locating cardiac structures in a known three-dimensional coordinate system by combining the multiplanar images with a probe localization system. In addition, the disclosed techniques are robust enough to use the images to detect and quantify cardiac drift that may occur during external beam therapy.

[0010] Some embodiments provide robustness in terms of image quality (e.g., ultrasound) by allowing imaging from different chest positions (particularly parasternal and apical viewing windows) depending on the patient's anatomy. Image processing methods are also designed with image quality robustness in mind. This can be beneficial for patients with advanced age or high BMI, common in arrhythmia patients, whose low echogenicity can lead to lower contrast ultrasound images.

[0011] Various embodiments of the present disclosure include redundancy that is an inherent part of the design. For example, if the imaging system fails to recognize the cardiac phase, the ECG signal can still be used to perform cardiac phase gating. In another example, in the event of such a failure of the imaging system, localization markers on the multiplanar probe may be utilized to track external motion and enable respiratory phase gating.

[0012] Various embodiments of the present disclosure enhance the alignment of the treatment patient with the particle beam. Standard clinical practice involves alignment with bony anatomy. In some embodiments, this bony anatomy alignment is supplemented with a cardiac alignment setup using ultrasound imaging.

[0013] Various embodiments of the present disclosure present systems and methods for cardiac ultrasound three-dimensional motion management. A multi-planar ultrasound probe is utilized, and dedicated image processing methods are disclosed for accurate and rapid identification of cardiac position and motion in three dimensions before and during external beam therapy. In some embodiments, methods are disclosed that allow accurate patient positioning based on cardiac position, monitoring of patient cardiac position drift during extended therapy sessions, and monitoring of respiratory motion during therapy.

[0014] The disclosed device and method are beneficial for the non-invasive treatment of cardiac arrhythmias. However, their use can also be advantageously applied to cancer treatment in the mediastinal and thoracic regions (breast, lung, among others), because in these cases, especially in the case of pencil beam scanning particle therapy, the treatment accuracy is affected by the position and motion of the heart. Indeed, in these clinical applications, the heart is not the target, but an important and delicate organ that clinicians do not want to harm in order to avoid serious side effects associated with radiation.

[0015] The disclosed devices and methods can also be applied outside the field of external beam radiation therapy, for example in radiology and interventional cardiology. In the case of radiology, it can provide a means to obtain better image quality using magnetic resonance imaging (MRI), computed tomography (CT) or other medical imaging modalities where cardiac motion can affect image quality (due to breathing and heart pulsation) and thus the derived measurements and diagnoses. This can, for example, avoid the use of breath-holding or forced ventilation techniques to limit respiratory motion. In the case of interventional cardiology, it can provide a means to monitor cardiac motion during an intervention. This allows the interventional cardiologist to, for example, only acquire X-ray images used for visualization of the catheter at the specific cardiac or respiratory state (motion phase) of interest. This allows a more efficient use of X-ray imaging, lowering the radiation dose delivered to both the patient and the medical staff and the operating costs.

[0016] In some embodiments, the disclosed devices and methods utilize B-mode ultrasound imaging. However, other imaging techniques are also contemplated, such as Doppler, elastography, M-mode imaging, and several other ultrasound imaging modalities. The present disclosure is also based on biplane ultrasound imaging utilizing orthogonal planes, but those skilled in the art, in light of the present disclosure, can more generally incorporate and employ imaging techniques such as non-orthogonal biplane images, triplane imaging, full volumetric imaging, or any other multi-planar ultrasound imaging geometry in three-dimensional space.

[0017] Conventional systems and procedures for extending and performing external beam radiotherapy treatments (radiotherapy, proton therapy, carbon ion therapy, among others) have certain drawbacks. Examples of drawbacks that are limitations in today's systems include patient set-up, organ drift during treatment, accounting for respiratory motion, and tracking anatomical structures in three-dimensional space.

[0018] Consider the problem of patient positioning in an external beam radiotherapy treatment of the heart. Before starting the course of an external beam radiotherapy treatment, a computed tomography (CT) scan of the patient is typically acquired in a so-called simulation phase. Subsequently, a patient-specific treatment plan is designed based on this CT scan, after which the treatment phase can begin, but generally not on the same day. During the treatment phase, the patient's position during the simulation phase is reproduced in the treatment room to ensure the validity of the treatment plan and the programmed beam parameters for the treatment delivery. Typically, immobilization devices such as thermoplastic masks, standard size wedges, wingboards and grabbers are used to assist in positioning the patient for a chest treatment. Currently available technologies to assist in this patient setup include biplane X-ray images, cone beam CT or CT on rails. Patient alignment in the treatment room is mainly based on the match of bony anatomical structures (using both manual and (semi)automated image registration) and of any soft tissues close to the target that have sufficient contrast in these images (e.g. tomographic imaging). The contrast of soft tissues such as the heart in these images is typically insufficient. The position of the heart also does not always correlate well with the bony anatomical structures. In addition, the patient's cardiac and respiratory movements further degrade the image quality. Image quality can also be affected by image artifacts caused by metal objects (especially pacemaker leads, implanted defibrillator leads) that are commonly present in the area of ​​interest. Thus, in arrhythmia and chest patient setups, there is generally limited anatomical information available in the acquired images, and as a result, there is a high degree of reliance on the judgment of the medical staff member.

[0019] The phenomenon and effects of cardiac drift are also considered. During external beam therapy treatment of cardiac arrhythmias, radiation doses in the range of 25-40 Gy can be delivered to a single treatment fraction. This is at least 2-3 times the typical stereotactic ablative radiotherapy dose for small thoracic lesions. In addition, special methods can be used to mitigate the effects of respiratory and cardiac motion on treatment accuracy during treatment. Both aspects (high dose requirements and motion mitigation) lead to fairly long treatment times with the patient typically immobilized in supine position. Thus, anatomical structures in the thorax / abdomen can relax, leading to a drift in the target position over time, referred to herein as "cardiac drift". Although methods of efficient intra-fraction motion management, such as MR-LINAC, are emerging, there is no standard method to monitor this drift during treatment without interrupting radiation beam delivery, which would further extend treatment time.

[0020] The influence of the respiratory cycle must also be managed. Periodic cardiac motion is characterized by two main components: cardiac (0.5-1.5 s period) and respiratory (3-5 s period). Previous work directed at such characterization includes Garonna et al., who outline the respiratory component but focus on cardiac motion aspects. For respiratory motion monitoring, systems are commercially available that indirectly monitor the internal motion of anatomical structures with the heart by tracing an external surrogate. These systems are based either on airflow into and out of the lungs (e.g., using a spirometer such as that utilized by the Active Breathing Regulator or ABC, a device supplied by Elekta AB, Stockholm, Sweden) or mechanical abdominal / thoracic motion resulting from contraction of the diaphragm, such as pressure belts (e.g., the ANZAI BELT (AZ-733VI) supplied by Anzai Medical Co., Ltd., Tokyo, Japan), optical tracking of chest motion (e.g., the RGSC system supplied by Varian Medical Systems, Inc., Palo Alto, California, USA) and X-ray tracking systems (e.g., the tracking system in the VERO® SBRT supplied by Brainlab AG, Munich, Germany). These approaches make assumptions about how the motion of the surrogate correlates with the internal motion of the anatomical structures and thus the behavior of the treatment target. If this correlation is weak, the accuracy of monitoring the target respiratory motion will be poor. Robotic radiosurgery systems (e.g., the CYBERKNIFE® supplied by Accuray Inc., Sunnyvale, Calif., USA) are capable of managing respiratory motion during radiation treatment. However, their use on the heart requires the implantation of fiducial clips.

[0021] Several techniques have been described in the literature that facilitate tracking of treatment targets on acquired three-dimensional ultrasound volumes of a particular anatomical structure or region of interest. Examples of clinically available systems are the CLARITY® and CLARITY® AUTOSCAN systems (supplied by Elekta AB, Stockholm, Sweden). In certain applications, volumetric imaging is required to track targets in three-dimensional space. Such requirements arise, for example, when the target may move outside the imaging plane, which is not necessarily detected in two-dimensional imaging, thereby leading to erroneous tracking. However, tracking of targets in three-dimensional space on three-dimensional ultrasound volumes has several limitations: · Existing commercial and research grade 3D ultrasound systems have inadequate spatial and temporal resolution. · It is sometimes necessary to manually identify targets or target surrogates whose motion correlates well with the motion of the target within the ultrasound volume. - 3D ultrasound imaging technology is bulky and expensive. At best, systems consisting of conventional techniques for tracking internal cardiac anatomy in three-dimensional space are estimated to have the following performance characteristics: The reaction time (the time between the appearance of an event and the final response of the system) is approximately 250 milliseconds (ms), which consists of 200 ms for 3D ultrasound volume acquisition, beamforming, and streaming of data from the ultrasound device to the host computer, and 50 ms for data interpretation. The spatial uncertainty of target localization is approximately 6.5 mm, which is a combination of 1 mm for ultrasound image localization in absolute room coordinates; 2.5 mm for surrogate segmentation and tracking accuracy in cases where the target or the target itself cannot be tracked appropriately; 2 mm for kinematic correlation between the target and target surrogate; and 1 mm for anatomy visualization differences between the planning CT scan and the ultrasound volume. Such performance characteristics are inadequate for cardiac external beam therapy procedures where reaction times of 100 ms or greater and spatial accuracy of 3 mm are expected.

[0022] This disclosure presents hardware and software components and methods that overcome certain present day limitations. Additionally, various clinical workflows are disclosed.

[0023] In some embodiments, an ultrasound imaging probe is disclosed that provides real-time non-invasive image acquisition without the use of ionizing radiation that can be potentially harmful to the patient. In addition, it is cost-effective, typically provides good soft tissue contrast, and is often the diagnostic tool of choice for cardiac patients.

[0024] Structurally, various embodiments of the present disclosure include a multiplanar motion management system for non-invasive cardiac ablation, the system including a multiplanar imaging probe configured to acquire live multiplanar images within a probe volume, the multiplanar images being non-parallel, a probe localization system configured to acquire position data of the multiplanar imaging probe, an input / output (I / O) management system configured to simultaneously receive the live multiplanar images and the position data and establish an acquisition time of the multiplanar images and the position data, and a gating system configured to receive and process the live multiplanar images, the position data, and the acquisition time. The gating system includes a processor, which may be configured to identify a cardiac phase corresponding to the live multiplanar image, define a set of reference coordinates from the position data that most closely corresponds in time to the live multiplanar image, and perform a rigid body registration of the live multiplanar image to the reference multiplanar image, the reference multiplanar image representing the cardiac phase. Some embodiments include a heartbeat detection system for generating cardiac cycle data, the heartbeat detection system configured to generate a trigger signal based on the cardiac cycle data, an I / O management system configured to receive the trigger signal contemporaneously with the multi-planar image and position data and generate trigger signal information including an acquisition time corresponding to the trigger signal, and a gating system configured to receive and process the trigger signal information to identify a start of a cardiac cycle. The gating system may be configured to utilize the trigger signal information to ascertain a cardiac phase. In some embodiments, the heartbeat detection system is an electrocardiogram (ECG) system, and the cardiac cycle data is generated from the ECG signal. The position data may be relative to a reference coordinate system, and the position data may identify a position and orientation of the multi-planar imaging probe in three-dimensional space. The multi-planar imaging probe may be configured to simultaneously acquire multi-planar images and may include a shape configured to be attached to a patient's chest. In some embodiments, the multi-planar imaging probe acquires multi-planar images at a rate in the range of 20 Hz to 50 Hz, inclusive.In some embodiments, the multi-planar imaging probe is a multi-planar ultrasound probe and the reference multi-planar image is an ultrasound image.

[0025] Various embodiments of the present disclosure embody a method including: (a) acquiring a series of reference multi-planar images of a beating heart in a patient using a multi-planar imaging probe; (b) acquiring a reference position of the imaging probe for each of the reference multi-planar images of the reference series of multi-planar images during step (a); (c) identifying a cardiac phase of each reference multi-planar image of the reference series of multi-planar images; (d) acquiring live multi-planar images using the multi-planar imaging probe during a beam therapy treatment of the patient; (e) acquiring a live position of the multi-planar imaging probe during step (d); (f) identifying a cardiac phase of the live multi-planar images; and (g) performing rigid body registration of the live multi-planar images and live positions to corresponding reference images of the reference series of multi-planar images and corresponding reference positions associated with the corresponding reference images, wherein the corresponding reference images represent cardiac phases of the live multi-planar images, and the rigid body registration provides a live cardiac position of the beating heart during the beam therapy treatment of the patient relative to a three-dimensional coordinate system to provide a live displacement of the beating heart relative to the reference positions.

[0026] In some embodiments, the method includes configuring steps recited as instructions on a tangible, non-transitory medium. The instructions in the configuring step include generating a status condition based on a comparison of the displacement to a predetermined threshold. The method may also include fastening a multiplanar imaging probe to the patient's chest for use during execution of a reference simulation. In some embodiments, the method includes fastening a multiplanar imaging probe to the patient's chest for use during execution of a simulation phase. The method may include instructing the patient to hold their breath for at least one cardiac cycle to achieve a known respiratory state. The known respiratory state may be an end-expiratory respiratory phase. The reference series of multiplanar images may be acquired at the beginning of a treatment process. In some embodiments, the reference series of multiplanar images may be acquired during a simulation phase prior to a treatment phase.

[0027] In some embodiments, the method includes coupling the multi-planar imaging probe and the probe localization system to a gating controller, the gating controller including a set of instructions for execution in real time preconfigured on a non-transitory computer readable medium. The instructions for the gating controller may include generating a status condition based on a comparison of the displacement to a predefined threshold. In some embodiments, the method includes configuring a non-transitory computer readable medium with instructions.

[0028] Various embodiments of the present disclosure include a method of locating a cardiac structure in a known three-dimensional coordinate system, the method including providing a multi-planar imaging probe and a location system for tracking the multi-planar imaging probe in three-dimensional space, and providing instructions on a tangible, non-transitory medium, the instructions including acquiring a first sequence of multi-planar images of the heart with the multi-planar imaging probe for the duration of a plurality of cardiac beats while the patient is in a known respiratory state and the heart is in a first position, locating the multi-planar imaging probe with the location system during acquiring the first sequence to define a first set of reference coordinates at the first position, acquiring a second sequence of multi-planar images of the heart with the multi-planar imaging probe for the duration of a plurality of cardiac beats while the patient is in a known respiratory state and the heart is in a second position, and locating the multi-planar imaging probe with the location system during acquiring the second sequence to define a first set of reference coordinates at the first position. , defining a second set of reference coordinates at the second position; identifying a first representative set of multiplanar images from the first sequence of multiplanar images and a second representative set of multiplanar images from the second sequence of multiplanar images, where the first representative set of multiplanar images and the second representative set of multiplanar images correspond to a known combination of cardiac motion phase and respiratory motion phase; aligning the second set of reference coordinates with the first set of reference coordinates; and quantifying translational and rotational displacements of the second representative set of multiplanar images relative to the first set of multiplanar images within the aligned first and second sets of reference coordinates. In some embodiments, the known combination of cardiac motion phase and respiratory motion in the identifying step corresponds to end-expiration of the respiratory motion phase. The instructions in the providing step include displacing the patient support according to the translational and rotational displacements. In some embodiments, the instructions in the step of providing instructions include instructing the patient to hold their breath for at least one cardiac cycle during the step of acquiring the first sequence of multiplanar images to achieve a known respiratory state. The step of acquiring the first sequence of multiplanar images of the instructions may be performed during an end-expiratory breathing phase to achieve a known respiratory state.

[0029] Various embodiments of the present disclosure include a method of inferring cardiac displacement resulting from respiratory motion from a multiplanar imaging probe attached to a patient's chest, the method including providing a multiplanar imaging probe and providing instructions on a tangible, non-transitory medium, the instructions including acquiring a reference series of multiplanar images with the multiplanar imaging probe, the multiplanar imaging probe being secured to the patient's chest, identifying a cardiac phase of each multiplanar image of the reference series of multiplanar images, acquiring live multiplanar images with the multiplanar imaging probe during a patient irradiation treatment, the multiplanar imaging probe being secured to the patient's chest, identifying a cardiac phase of the live multiplanar images, and performing rigid body registration of the live multiplanar images to corresponding images of the reference series of multiplanar images, the corresponding images of the reference series representing the cardiac phase of the live multiplanar images. [Brief description of the drawings]

[0030] [Figure 1] FIG. 1 is a perspective view of an ultrasound probe for acquiring multi-planar images in two non-parallel imaging planes according to an embodiment of the present disclosure. [Diagram 2] FIG. 1 is a perspective view of an ultrasound probe for acquiring multi-planar images in two non-parallel imaging planes according to an embodiment of the present disclosure. [Diagram 3] FIG. 1 is a simplified perspective view of a non-invasive cardiac ablation system according to one embodiment of the present disclosure. [Figure 4] FIG. 4 is a schematic diagram of the non-invasive cardiac ablation system of FIG. 3 according to one embodiment of the present disclosure. [Diagram 5] FIG. 1 is a workflow diagram illustrating the simulation stages of creating a treatment plan, according to one embodiment of the present disclosure. [Figure 6] FIG. 1 is a workflow diagram illustrating the treatment steps for delivering radiation therapy, according to one embodiment of the present disclosure. [Figure 7] 13 illustrates alignment of a treatment stage image with a simulation stage image according to one embodiment of the present disclosure. [Figure 8] 13 illustrates alignment of a treatment stage image with a simulation stage image according to one embodiment of the present disclosure. [Figure 9] 13 illustrates alignment of a treatment stage image with a simulation stage image according to one embodiment of the present disclosure. [Figure 10] 11 is a plot illustrating live-simulation registration and cardiac displacement localization characteristics for analysis of respiratory cycle and cardiac drift, according to an embodiment of the present disclosure. [Figure 11] 11 is a flowchart of a method for extracting respiratory cycle and cardiac drift information of FIG. 10 according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0031] 1 and 2, the operation of a multiplanar ultrasound probe 50 according to an embodiment of the present disclosure is illustrated. The multiplanar ultrasound probe 50 is configured to acquire images in two non-parallel imaging planes 52 and 54. In some embodiments, the non-parallel imaging planes 52 and 54 are orthogonal to each other and are arbitrarily referred to as the xy plane (FIG. 2) and the xz plane (FIG. 3). The multiplanar ultrasound probe 50 includes a two-dimensional array of sensors (not shown) that can be scanned to provide an active probe volume 56. The multiplanar ultrasound probe 50 can image each of the multiplanar images with similar resolution characteristics as a single two-dimensional ultrasound image. Such multiplanar ultrasound probes are commercially available, for example the XMATRIX® X5-1 or X7-2t array transducers provided by Koninklijke Philips Electronics NV, Eindhoven, The Netherlands.

[0032] In some embodiments, the probe design is configured to reduce the number of metal components inside the case, thereby reducing the appearance of artifacts, for example, in CT imaging or cone-beam CT imaging. The multiplanar ultrasound probe 50 may have a shape (not shown) adapted for positioning on the chest of a patient 58 (FIG. 4). In some embodiments, the multiplanar images are acquired at an image refresh rate in the range of at least 10 to 30 Hertz, inclusive. In some embodiments, the image refresh rate is in the range of 10 to 50 Hertz, inclusive. In some embodiments, the image refresh rate is in the range of 10 to 100 Hertz, inclusive. As used herein, ranges written as "inclusive" include the endpoints of the stated range.

[0033] Functionally, multiplanar ultrasound probe 50 allows for simultaneous or sequential live acquisition of non-parallel images (FIG. 4), where "live" is defined as real-time acquisition or near real-time acquisition sufficient for image monitoring. Non-parallel images acquired with multiplanar ultrasound probe 50 allow for monitoring of cardiac motion in three-dimensional spatial coordinates within active probe 56. Non-parallel imaging planes 52 and 54 provide information in three dimensions about the imaged anatomical structures.

[0034] 3 and 4, a non-invasive cardiac ablation system 100 according to one embodiment of the present disclosure is shown. The non-invasive cardiac ablation system 100 includes a treatment beam delivery system 102, a patient positioning system 104, a multi-planar imaging system 106, a probe localization system 108, and a heartbeat detection system 110. The systems 106, 108, and 110 are controlled by a real-time data acquisition system or DAQ 112, which are all part of an input / output (I / O) management system 114. The I / O management system 114 interfaces with a beam gating system 116 to present a multi-planar motion management system 118. The I / O management system 114 may also include an auxiliary interface 120 for interfacing with other components of the non-invasive cardiac ablation system 100, such as the patient positioning system 104.

[0035] The I / O management system 114 acquires data sets from different data streams simultaneously and establishes an acquisition time ("timestamp") corresponding to each data set. In some embodiments, the I / O management system 114 includes components for acquiring three types of data: ultrasound data, electrocardiogram (ECG) data, and optical localization data. The I / O management system 114 may be physically located within the treatment room 122 and, in some embodiments, may be housed or based within an I / O cabinet 124.

[0036] The multiplanar imaging system 106 is coupled to a multiplanar imaging probe 126 (e.g., a multiplanar ultrasound probe 50) to generate non-parallel multiplanar images 128 in real time or near real time for visualization of the heart. The multiplanar imaging system 106 may include a multiplanar ultrasound probe 50, a probe holder 142, and a beamformer (not shown). The beamformer generates timed electrical signals that send ultrasound waves into the patient, collects electrical signals from the probe elements based on reflections of acoustic waves off the patient, and processes the input signals to generate an ultrasound image.

[0037] The multiplanar image 128 may directly resolve the target area 146 or may otherwise allow for inference of the location of the target area 146. The multiplanar imaging probe 50, 126 and / or the probe holder 142 may include or be fitted with one or more localization markers 144. The multiplanar imaging system 106 may be configured to withstand a certain level of radiation exposure, such as indirect emissions of neutrons, protons and gamma rays from nearby particle beams. Alternatively, some components of the multiplanar imaging system 106 (e.g., data processor) may be remote or signals transmitted via analog or digital transmission cables.

[0038] The use of a multiplanar ultrasound probe 50 as the multiplanar imaging probe 126, which is prevalent throughout this disclosure, is non-limiting. Those skilled in the art will recognize in light of this disclosure that the concepts disclosed herein are not limited to ultrasound imaging, but may incorporate other non-parallel imaging devices and techniques, which may be incorporated mutatis mutandis. Other multiplanar imaging systems 106 and associated multiplanar imaging probes 126, such as X-ray, MRI and ECGI systems, are also contemplated for the noninvasive cardiac ablation system 100.

[0039] The probe localization system 108 may be an optical system, such as a camera 152, fixed to view the localization marker 144. In one embodiment, the camera 152 is an infrared (IR) camera, such as a FUSIONTRACK® 500 available from Atracsys, SARL, Puidoux, Switzerland, or a POLARIS VEGA® XT available from Northern Digital Inc., Waterloo, Canada. This type of camera can locate, for example, infrared reflective or LED markers with six degrees of freedom in three-dimensional space in the form of position data that establishes the position and rotational orientation of the marker relative to the camera 152. Alternatively, the probe localization system 108 may operate by other principles, including electrical, magnetic, or acoustic. The probe localization system 108 may also include surface tracking capabilities, for example, using laser or thermal imaging.

[0040] In some embodiments, the localization markers 144 are located in a CT room (not shown) during the simulation phase 200 (FIG. 5) and in the treatment room 122 during the treatment phase 300 (FIG. 6). The CT room and the treatment room may include a common room or reference coordinate system 154 that generates reference pixel coordinates 156′, 156 relative to a treatment isocenter (not shown) of the non-invasive cardiac ablation system 100, the reference pixel coordinates 156′ referencing the simulation phase 200 and the reference pixel coordinates 156 referencing the treatment phase 300. A calibration procedure using a dedicated calibration phantom (not shown) may be used so that the probe localization system 108 provides the position and orientation of the multiplanar imaging probe 50, 126 in the matching room coordinate system 154. Such calibration phantoms are known in the art, for example as used by Lachaine et al., “Intrafractional prostate motion management with the Clarity Autoscan system”, Medical physics international, 1 (2013).

[0041] The heartbeat detection system 110 generates cardiac cycle data 158, such as an ECG, that measures electrical activity generated by the heart. The heartbeat detection system 110 monitors the cardiac signal acquisition and outputs a trigger signal, which is received by the I / O management system 114. In some embodiments, the I / O management system is configured to receive the trigger signal simultaneously with the multi-planar image 128. The ECG system may monitor both the amplitude of the electrocardiogram signal and an R-peak trigger. The ECG system outputs a trigger pulse upon R-peak detection, which is received and time-stamped by the I / O cabinet. The ECG system may also control switching between ECC leads.

[0042] The DAQ 112 controls at least the systems 106, 108 and 110 and may include a programmable logic controller (PLC) 162 and various I / O modules 164. The PLC 162 and I / O modules 164 perform start and stop triggering and precise time stamping of the imaging, cardiac and localization data streams.

[0043] The treatment beam delivery system 102 and the patient positioning system 104 are optionally coupled to the I / O management system 114. The treatment beam delivery system 102 may include a particle emitter 166 and a beam controller 168 that selectively generate a particle beam 170 that is delivered to the target region 146. The patient positioning system 104 may include a patient support 172 and a positioner system 174. In some embodiments, the non-invasive cardiac ablation system 100 includes a patient localization system 176 that may also be coupled to the I / O management system 114. The patient localization system 176 may include a dual x-ray or cone beam computed tomography (CBCT) imaging system to verify patient position. Further details of the treatment beam delivery system 102, the patient positioning system 104 and the patient localization system 176 can be found in Garonna et al.

[0044] The beam gating system 116 includes hardware control and signaling capabilities coupled to a gating controller 178. The target motion management system 118 may include a control console 180 for user interfacing with the gating controller 178. The control console may include a graphical user interface (GUI) 182 to facilitate user input and information display. The gating controller 178 is operatively coupled to receive input from and / or send output to the treatment beam delivery system 102, the patient positioning system 104, and the multiplanar imaging system 106. The gating controller 178 may interface with the I / O management system 114 via the DAQ 112. In addition to controlling and coordinating the hardware components of the non-invasive cardiac ablation system 100, the gating controller may include computer memory for storing and executing various required computational tasks of the beam gating system 116, including, but not limited to, multiplanar image registration, cardiac phase identification (e.g., according to Garonna et al.).

[0045] The beam gating system 116 processes the data and generates updates to the user and the non-invasive cardiac ablation system 100. The beam gating system 116 may be used, for example, to process the image, heartbeat, and localization data streams in real-time or near real-time using a graphics processing unit (GPU) 184. Alternatively, the GPU 184 may be located in the treatment room 122 and housed in the I / O cabinet 124 as part of the I / O management system 114. The GPU 184 may communicate with a GUI 182 and an auxiliary display monitor 186 that display data such as the multi-planar images 128 and cardiac cycle data 158. The beam gating system 116 may also receive information from an operator through the GUI 184. The beam gating system 116 may be remotely located in a control room 188 separate from the treatment room 122 and, in some embodiments, is housed in or based on a workstation platform 192.

[0046] The beam gating system 116 may also include an interface 194 that communicates with the beam controller 168 via a communication channel 196. The communication channel 196 may be an analog or digital cable or a wireless channel. The beam gating system 116 transmits a gating signal via the communication channel 192 to enable or gate the particle emitter 166. As used herein, "enabling" the treatment beam delivery system 102 is to allow the particle beam 170 to irradiate the patient 58, while "gating" the treatment beam delivery system 102 is to prevent the particle beam 170 from irradiating the patient 58. More generally, the term "beam gating" refers to transmitting a signal to the beam controller 168 to pause or resume delivery of the treatment beam 170 as planned. The manner in which such enabling and gating is accomplished is system specific. Some systems enable the particle beam 170 by activating an accelerometer of the treatment beam delivery system 102 and gate the particle beam 170 by deactivating the accelerometer. Other systems leave the accelerometer activated and gate the particle emitter 166 by blocking or delivering the particle beam 170 so that the patient 58 is not irradiated.

[0047] Functionally, the probe localization system 108 enables tracking of the multi-planar imaging probe 50, 126 in three-dimensional space in order to associate the localization markers 144 with anatomical structures in the multi-planar image 128. The probe localization system 108 enables localization and continuous monitoring of the localization markers 144 in a room coordinate system 154.

[0048] The probe localization system 108 can be used for monitoring respiratory motion. The multiplanar imaging probe 50, 126 and / or the probe holder 142, equipped with localization markers 144, is placed on the chest to image the heart and appropriately positioned to follow the tidal motion of breathing. The localization markers 144 can thus act as external surrogates for respiratory motion. The probe localization system 108 can thereby provide external information about the respiratory motion in the vicinity of the heart and the target region 146.

[0049] In operation, the multiplanar motion management system 118 can be used during a simulation phase 200 (FIG. 5) prior to treatment delivery and / or during a treatment phase 300 (FIG. 6) in which treatment delivery is performed. The multiplanar imaging probe 50, 126 can be secured to the patient 58 using a probe holder 142, for example, on the patient's 58 chest for parasternal and apical viewing windows. The multiplanar imaging probe 50, 126 is immobilized on the patient's 58 chest using the probe holder 142 to allow hands-free operation. In some embodiments, signal processing of the beamformer of the multiplanar ultrasound probe 50 is utilized to reconstruct the image for visualization.

[0050] The multiplanar imaging system 106 may provide continuous visualization of the heart transperitoneally (through the diaphragm or liver) or transthoracic (between the ribs). The multiplanar imaging probes 50, 126 may be non-parallel, may be placed in apical or parasternal positions, and / or may image long-axis or short-axis cardiac structures affected by cardiac motion.

[0051] The non-invasive cardiac ablation system 100 also delivers the particle beam 170 to the target region 146 at predetermined phases of certain body motion cycles. Such body motion cycles may include respiratory and cardiac cycles. The multiplanar imaging system 106 provides multiplanar images 128 from real-time imaging to the target motion management system 118. The target motion management system 118 utilizes the multiplanar images 128 to deliver the particle beam 170 at predetermined respiratory and cardiac phases, for example, as described by Garonna et al. The multiplanar images 128 may also include information regarding desired properties of the particle beam 170, which may also be determined by a gating controller 178.

[0052] The multi-planar images 128 and cardiac cycle data 158 can be continuously acquired and updated to the target motion management system 118, providing a live stream of information to the operator. The multi-planar images 128 and cardiac cycle data 158 can be stored in a storage medium and later analyzed to assess the accuracy of the phase prediction process, employing patient 58 specific software parameters as needed.

[0053] With reference to FIG. 5, a workflow of a simulation stage 200 according to an embodiment of the present disclosure is shown. During the simulation stage 200, all data and anatomical information (e.g., medical images) required for treatment planning are collected, from which a patient-specific treatment plan is created. The simulation stage 200 may include a series of processes, each of which is illustrated in FIG. 5 by a reference letter beginning with the letter "p". The processes of the simulation stage 200 may include a localization system calibration process (p210), which in some cases may only be performed intermittently; a subject setup process (p220); a reference imaging process (p230); a planning CT scan process (p240); a contouring process (p250); and a treatment planning process (p260). The various processes are illustrated as including one or more steps illustrated in FIG. 5 by a reference letter beginning with the letter "s".

[0054] In some embodiments, the localization calibration process (p210) of the simulation stage 200 is performed in a CT imaging room and includes calibration (s211) of the probe localization system 108 using a specifically designed calibration phantom. The calibration phantom step (s211) enables the multiplanar imaging probe 50, 126 to be localized in the room coordinate system 154 (e.g., of the CT imaging room) in subsequent processes and stages. A patient or subject setup process (p220) is performed in which the patient 58 is positioned on the CT table according to an oncological radiation treatment procedure. The subject setup process (p220) may include the use of standard immobilization and patient support devices.

[0055] A reference imaging process (p230) is performed, and reference multiplanar images are acquired with a multiplanar imaging probe 50, 126 (s231) fixed to the patient's chest using a probe holder 142 (s234). During image acquisition, the multiplanar imaging probe 50, 126 may be located by the probe localization system 108 using the localization markers 144 (s232). In this way, the position of the multiplanar imaging probe 50, 126 during acquisition of each reference multiplanar image (referred to herein as the "reference position") may be identified with respect to the room coordinate system 154 (s235). The cardiac phase of each reference multiplanar image acquired in the reference imaging process p230 is identified (s233). During acquisition of the reference multiplanar images, skin markers may be placed on the skin of the patient 58 (s236) to assist in repositioning the multiplanar imaging probe 50, 126 during the treatment phase 300 (FIG. 6). In some embodiments, cardiac cycle data 158 is acquired during the simulation phase (s237). Additionally, the time resolved positions of the localization markers 144 can be used as a respiration signal (s238).

[0056] In some embodiments, the planning CT scan process (p240), the contouring process (p250) and the treatment planning process (p260) of the simulation stage 200 may implement standard oncology radiation therapy procedures. The planning CT scan process (p240) may include planning a four-dimensional (three spatial dimensions plus time) computed tomography (4D-CT) scan acquisition. In some embodiments, a dummy probe is utilized during the acquisition of the CT acquisition plan (s241) to avoid undesirable artifacts on the CT scan generated by metallic parts of the multiplanar imaging probe. The dummy probe may also be localized by the probe localization system 108 using localization markers (s242). Additional cardiac cycle data and respiratory data may also be acquired (s244-s247). In the 4D-CT scan, both respiratory gating and cardiac gating may be performed. During the contouring process (p250), the radiation target is contoured and generally, the organs at risk near the target region 146 are also contoured. One example of a relevant contouring process can be found in Blanck et al., “Radiosurgery for ventricular tachycardia: preclinical and clinical evidence and study design for a German multi-center multi-platform feasibility trial (RAVENTA)”, Clin Res Cardiol 109, 1319-1332 (2020).

[0057] In some embodiments, during the planning CT scan process (p240), two heartbeat signals are acquired. The planning CT scan is typically reconstructed using data from heartbeat signal #1 (s244), acquired by a first heartbeat detection system directly connected to the CT scanner. Treatment delivery is based on heartbeat signal #2 (s245), acquired by the heartbeat detection system 110 of the I / O management system 114. In ECG systems, the start of the cardiac cycle is typically identified using R-peak information, but different ECG suppliers typically have their own way of identifying the R-peak (e.g., just before or just after the actual peak). Thus, the disclosed embodiments include the provision of simultaneously acquiring signals from both heartbeat detection systems to establish a correlation between the R-peak identifications of each heartbeat detection system. Alternatively, the CT scanner may use heartbeat signal #2 from the heartbeat detection system 110 instead of its own heartbeat signal #1, or the I / O management system 114 may use heartbeat signal #1 from the CT scanner instead of its own heartbeat signal #2, thereby eliminating the need for correlation.

[0058] Similarly, in some embodiments, two respiratory signals RESP#1 and RESP#2 may be acquired during the planning CT scan process (p240). The planning CT scan is reconstructed using data from RESP#1 (s247) (or any other respiratory motion surrogate signal), which may be acquired by a first localization system available in the CT imaging room. Treatment delivery is based on RESP#2 (s246), which may be acquired by the probe localization system 108 of the I / O management system 114. Each localization system may have peculiarities that require correlation. For example, when localization is performed with multiple optical tracking systems, aspects of one optical tracking system may differ from the characteristics of the other optical tracking systems. Such aspects include the position of the optical tracking system relative to the tracked object, acquisition rate, and acquisition latency. Thus, the disclosed embodiments include simultaneously acquiring signals from both localization systems to establish correlation between the respiratory motion detected by each localization system. Alternatively, the CT imaging room may use RESP#2 from the probe localization system 108 instead of its own RESP#1, or the I / O management system 114 may use RESP#1 from a localization system used in the CT imaging room instead of its own RESP#1, eliminating the need for correlation.

[0059] In some embodiments, the treatment planning process (p260) includes determining three input characteristics of the treatment phase 300: (1) the desired location of the treatment isocenter (s261) in coordinates provided by the room coordinate system 154, (2) a cardiac gating window (s262) provided by the treatment plan that determines when the radiation beam should be enabled or disabled based on cardiac motion, and (3) a respiratory gating window (s263) provided by the treatment plan that determines when the radiation beam should be enabled or disabled based on respiratory motion. Additionally, the treatment planning process generates contours of the target and all associated organs on at least one reference CT.

[0060] Referring to FIG. 6, a workflow of a treatment stage 300 according to an embodiment of the present disclosure is shown. The treatment stage 300 facilitates precise delivery of radiation dose to a target while sparing as much surrounding normal tissue as possible. The treatment stage 300 includes a series of processes, each of which is indicated in FIG. 6 by a reference letter beginning with the letter "p". The processes may include a localization system calibration process (p310), which in some cases may only be performed intermittently; a subject setup process (p320); a multiplanar probe setup process (p330); a bone alignment process (p340); a cardiac alignment process (p350); a treatment initiation process (p360); and a gating process (p370). Various processes are indicated as including one or more steps indicated in FIG. 6 by a reference letter beginning with the letter "s".

[0061] In some embodiments, the treatment phase 300 begins with a calibration (p310) of the probe localization system 108, again using a calibration phantom (s311). During the subject setup process (p320), the patient 58 is positioned on the table in the same manner as in the simulation phase 200. In some embodiments, an initial alignment of the skin marks with the treatment room isocenter is performed during the subject setup process (p320), for example, using a laser system available in the treatment room or using a surface imaging system. The multiplanar imaging probe 50, 126 is positioned and immobilized on the chest of the patient 58 using the probe holder 142 (s333). Information from the skin marks and localization markers (s332) can be utilized to facilitate positioning the multiplanar imaging probe 50, 126 on the patient 58 in the same position as during the simulation phase.

[0062] With the multiplanar imaging probe 50, 126 in a fixed position, the patient 58 is aligned using the room coordinate system 154. In some embodiments, the bone alignment process (p340) includes aligning the patient 58 based on the bone anatomy, for example using cone beam CT (s341). During the table alignment step (s342), the alignment misalignment is calculated based on a comparison of the bone anatomy from the simulation phase 200 and the treatment phase 300, identified, for example, using CT, CBCT or X-ray images. The alignment misalignment is corrected by scanning the patient support 172 using the patient positioner 174 to align the patient 58 with the simulation orientation. In some embodiments, the correction is performed using the multiplanar motion management system 118 via one of the auxiliary interfaces 120 to control the patient positioning system 104.

[0063] During the cardiac alignment process (p350), live multiplanar images are acquired and registered with the reference multiplanar images acquired during the simulation phase 200 (at s235 of p230 of FIG. 5). This rigid registration (s351) is generally referred to as "live-simulation" image registration and is performed between images of the same data type. For example, when using a multiplanar ultrasound probe 50, the live and simulated images are both ultrasound images and can be referred to as "inter-ultrasound" or "inter-US" image registration. The process is generally applied regardless of whether the multiplanar images 128 are ultrasound images or not. In some embodiments, the inter-ultrasound image registration serves as a final check of the patient setup. In a table fine-tuning step (s353), the alignment misalignment is calculated based on a comparison of the cardiac soft tissue contrast from the simulation phase 200 and the treatment phase 300 identified using the multiplanar images 128. The translations and rotations required to correct the alignment misalignment are performed using the positioner system 174, optionally using the multiplanar motion management system 118.

[0064] At the start of the treatment and gating processes (p360 and p370), live multiplanar images are continuously acquired in real-time or quasi-real-time (s371) while the probe localization system 108 simultaneously tracks (s372) the multiplanar imaging probe 50, 126. Cardiac phases are identified live in each reference multiplanar image acquired in the reference imaging process p230 (s233). Based on the live multiplanar images, four different outputs are generated: (1) cardiac displacement information for drift monitoring (p374), (2) respiratory gating signal (s375), (3) cardiac gating signal (s376) (e.g., as disclosed in Garonna et al.), and (4) associated warnings and interlocks (s377), such as patient physiological changes requiring treatment and interruption of treatment.

[0065] 7-9, a patient setup method 400 is shown that enhances alignment of the patient to the correct position in the room coordinate system 154, according to one embodiment of the present disclosure. The patient setup method assists in setting up the patient 58 in the treatment phase 300 in the same position and orientation as in the simulation phase 200 by supplementing the bone alignment setup with a cardiac alignment setup using multiplanar imaging. The patient setup method 400 may be accomplished during the cardiac alignment process (p350) of the treatment phase 300. Aspects of the method are outlined below.

[0066] During the simulation phase 200, during localization of the multiplanar imaging probe 50, 126 (FIG. 5), a simulation phase image sequence SIM is acquired over the duration of one or more cardiac beats and one or more respiratory cycles. Similarly, during the treatment phase 300, during localization of the multiplanar imaging probe 50, 126 (FIG. 6), a treatment phase image sequence TX is acquired over the duration of one or more cardiac cycles and respiratory cycles.

[0067] From both the SIM and TX sequences, multi-planar images 128 belonging to a particular combination of cardiac and respiratory motion phases are extracted (step 400a in FIG. 7 ), and simulation phase reference pixel coordinates 156′ and treatment phase reference pixel coordinates 156 are defined. For example, images correlating with end-expiration respiratory phase and end-systolic cardiac phase can be extracted from each sequence. In this way, cardiac and respiratory motions are in the same physiological state in the images extracted from the SIM and TX sequences. The identification of a known respiratory state can be performed by a gating controller. Such known respiratory states include, but are not limited to, breath-hold or end-expiration situations. The identification of an end-systolic cardiac phase or other preferred cardiac phase can also be identified by the gating controller.

[0068] A coarse rigid registration is performed in step 400b (FIG. 8). The coarse rigid registration overlaps images 402 and 402' from the SIM and TX sequences. The coarse rigid registration is based on the position of the active probe volume 56 at the time of image acquisition (step 400b in FIG. 8). The coarse rigid registration 400b is performed without regard to the content of the SIM and TX images 402 and 402'.

[0069] A fine rigid registration is also performed (at step 400c in FIG. 9) based on the content of the SIM image 402 and the TX image 402'. The combination of the coarse and fine registration quantifies the translational and rotational displacement of the heart in the treatment phase 300 relative to the simulation phase 200. Thus, the patient setup method (processes p320, p340 and p350 of the treatment phase 300 in FIG. 6) may provide translational and rotational instructions to the patient positioning system 104 for displacing the patient support 172 of the non-invasive cardiac ablation system 100 on which the patient 58 is positioned in order to properly align the heart of the patient 58 with respect to the simulation phase setup (steps s342 and S353 in FIG. 6). The basic concepts of coarse rigid registration and fine rigid registration are disclosed in Khalil et al., “An Overview on Image Registration Techniques for Cardiac Diagnosis and Treatment”, Cardiology research and practice, 2018 (2018) and Che et al., “Ultrasound registration: A review”, Methods, 115, 128-143 (2017).

[0070] The above techniques can also be used to monitor cardiac displacement or "drift" at the reference pixel coordinates 156 during the treatment phase 300. That is, cardiac drift can also be measured with respect to the SIM image 402. The information can be visualized in the GUI 182, allowing the operator to halt the treatment if they deem it necessary. In some embodiments, based on input provided by the operator prior to treatment delivery, the non-invasive cardiac ablation system 100 can automatically trigger a warning and / or interlock and halt the particle beam 170, for example if the heart moves outside the planned target margin (taking into account motion uncertainties) for too long.

[0071] In some embodiments, external and internal information are combined to monitor cardiac motion due to respiration. The placement of the multiplanar imaging probe 50, 126 and associated localization markers 144 on the patient's chest (s332, s333 in FIG. 6) provides external information, as described above. The multiplanar image 128 provides internal information about cardiac motion due to respiration. In effect, the multiplanar image 128 contains information about the cardiac motion and the motion of the multiplanar imaging probe 50, 126 at the reference pixel coordinates 156.

[0072] The combination of both extrinsic and intrinsic information provides an accurate representation of cardiac motion, whereas relying on extrinsic information can only inaccurately estimate cardiac motion based on the movement of surrounding anatomical structures such as the lungs. The combination of intrinsic and extrinsic information for respiratory motion management is an improvement over conventional systems and techniques that are often limited to extrinsic information provided by an external surrogate.

[0073] With reference to Fig. 10, various aspects of respiratory motion information according to an embodiment of the present disclosure will be discussed. The multiplanar image 128 inherently captures both the displacement of the heart relative to the multiplanar imaging probe 50, 126 (resulting from the displacement of anatomical structures inside the chest) and the displacement of the multiplanar imaging probe 50, 126 itself (resulting from the expansion and contraction of the chest). These combined displacements can be separated and extracted from the multiplanar image 128 by a rigid registration process. Probe localization allows the two contributions to be separated. The registration process allows the cardiac displacement to be identified.

[0074] In some embodiments, at the start of treatment (e.g., during treatment start process p360 of FIG. 6), a series of reference multiplanar images of the patient's beating heart are acquired when the patient is in a known respiratory state. The patient may be asked to hold his / her breath for one or more cardiac cycles, for example, as shown in breath-hold situation 412. For each reference multiplanar image in this breath-hold or reference sequence 412, no motion due to breathing is present, and periodic motion due to cardiac motion may be extracted based on cardiac cycle data 158 or with respect to cardiac phase as described in Garonna et al. Alternatively, instead of generating a reference multiplanar image at the start of treatment, a SIM image 402 (acquired at s235 of p230 of FIG. 5) generated during the simulation phase 200 may be used.

[0075] During the treatment phase 300, a series of live multiplanar images are acquired. A rigid registration of each live multiplanar image to a reference multiplanar image of the corresponding cardiac phase is performed. For example, if the cardiac phase of a given live multiplanar image is identified as 0.3, then the live multiplanar image is registered to a reference multiplanar image that corresponds to or represents the same cardiac phase as 0.3. This rigid (live-simulation) image registration may be similar to the steps of TX-SIM registration described in conjunction with FIGS. 7-9 and may include fine and coarse registration.

[0076] During the procedure, the patient is allowed to breathe normally, as shown in the fine rigid registration time trace 414 during normal breathing situation 416. The fine registration time trace 414 of the live-simulation images indicates the displacement of the heart relative to the probe, since the images themselves do not provide an indication of the spatial location of the probe volume 56 during acquisition. A localization marker time trace 418 is also presented in FIG. 10, presenting the displacement of the localization markers 144 during normal breathing situation 416. The localization marker time trace 418, in contrast, only provides an indication of the positional displacement of the probe volume relative to room coordinates. The live multiplanar images acquired during normal breathing 416 are registered to a reference multiplanar image of the corresponding cardiac phase. Due to the cardiac phase correlation of the reference and live multiplanar images, any relative displacement due to cardiac activity is substantially cancelled by the rigid registration, such that any displacement indication after rigid registration of the live-simulation (inter-ultrasound) images is primarily due to respiratory motion and / or cardiac drift relative to the multiplanar imaging probe 50, 126. Therefore, cardiac motion due to respiration can be inferred from the difference between the rigid body registration time trace 414 and the localization time trace 418.

[0077] Estimation of cardiac motion due to respiration is achieved by full (coarse and fine) registration, which is also illustrated in FIG. 10. The full registration procedure is as follows: The difference Δ between the fine rigid registration time trace 414 and the localization (coarse registration) time trace 418 is illustrated in graph 410 at time t=30 seconds. The difference Δ may be with reference to the registration time trace 414, in which case the value of Δ illustrated at t=30 seconds is negative or inverted (represented by a downward arrow in graph 410). A subplot 420 presenting a difference time trace 422 of the difference Δ as a function of time is also provided in FIG. 10. The cyclical aspect of the difference time trace 422 represents cardiac motion due to respiration, providing a reliable dynamic indication of the respiratory cycle for purposes of respiratory gating or motion monitoring.

[0078] Detection of cardiac drift is also shown in subplot 420. In general, an upward transition of the fine registration time trace 414 relative to the localization time trace 418 in the graph 410 indicates cardiac drift. Cardiac drift is indicated in subplot 420 by a downward transition of the difference time trace 422. The cause of the opposite transition of the time traces 414 and 422 is a magnitude reversal of the difference Δ. Over the initial respiratory cycle of the normal respiratory phase 416, a median data line 424 may be established that represents the difference Δ being zero. An operating band 430 is bounded by a lower threshold 426 and an upper threshold 428 of the difference Δ on the subplot 420. The operating band represents an acceptable range of difference Δ within which the noninvasive cardiac ablation system 100 can operate. The difference time trace 422 is shown exceeding the lower threshold 426 of the operating band 430 at an exit point 432 and returning within the operating band 430 at a re-entry point 434. Thus, there is a hole 436 in the operating zone 430 between the exit point 432 and the re-entry point 434 .

[0079] In some embodiments, the beam gating system 116 is configured to gate or disable delivery of the treatment beam 170 when the difference Δ is outside the operating band 430. The beam gating system 116 can also be configured to enable delivery of the treatment beam 170 when the difference Δ re-enters the operating band 430. In some embodiments, the beam gating system 116 is configured to gate delivery of the treatment beam 170 only if the hole 436 exceeds a predetermined amount of time. Similarly, the beam gating system 116 is configured to enable delivery of the treatment beam 170 only if the re-entry into the operating band exceeds a predetermined amount of time. In some embodiments, the upper and lower thresholds 426 and 428 are entered by a system operator using, for example, the control console 180.

[0080] Graph 410 of Figure 10 is included for illustrative purposes and presents one-dimensional displacement data along a single coordinate. In light of this disclosure, one skilled in the art will recognize that multi-planar imaging probes 50, 126 provide information in three dimensions and therefore can provide displacement information in three dimensions.

[0081] The time traces 414 and 418 have the same time pattern because they are both the result of patient respiration. Thus, the localization marker time trace 418 may provide redundancy to act as a check to the live-simulation image registration. If the live-simulation (e.g., US-to-US) registration fails to monitor the localization markers 144, the localization may also provide a backup to identify the respiratory phase. Additionally, the information provided by the localization markers may provide additional information that can be used to further understand how the anatomical structures around the heart are located.

[0082] 11, a method for extracting respiratory motion information from a multi-planar image 128 based on the respiratory motion aspects discussed in FIG. 10 is shown according to an embodiment of the present disclosure. A reference multi-planar image of a beating heart in a patient is acquired using a multi-planar imaging device (s451); a reference position of an imaging probe at the reference multi-planar image of step 451 is simultaneously acquired (s452); a cardiac phase of the reference multi-planar image of step s451 is identified (s453); steps s451-s453 are repeated to acquire a series of reference multi-planar images and corresponding probe positions and cardiac phases (s454). The series of reference multi-planar images are stored, for example in a computer-readable storage medium of the gating controller 178, for access during a treatment process p460.

[0083] The treatment process 460 continues: during the patient's beam therapy treatment, acquire live multiplanar images using the multiplanar imaging probe (s466); simultaneously acquire live positions of the multiplanar imaging probe (s467); identify cardiac phases of the live multiplanar images (s467); perform rigid registration of the live multiplanar images and live positions with corresponding images of the reference sequence and corresponding reference positions associated with corresponding reference images acquired in step 455, the corresponding reference images representing cardiac phases of the live multiplanar images. The rigid registration provides a live cardiac position of the beating heart during the patient's beam therapy treatment relative to a three-dimensional coordinate system and provides a live displacement of the beating heart relative to the reference positions. In some embodiments, a status condition based on a comparison of the displacement with a predefined threshold is generated for updating by the beam gating system 116. Steps s461-s466 are repeated for the duration of the external beam therapy treatment.

[0084] In some embodiments, the steps of the various methods disclosed herein are provided in the form of instructions provided on a tangible, non-transitory medium, such as a printed document, a compact disc, or a flash drive. Non-limiting examples of tangible, non-transitory media include paper documents and computer-readable media, including compact discs and magnetic storage devices (e.g., hard disks, flash drives, cartridges, floppy drives). The computer-readable media may be local or accessible via the Internet. The instructions may be completed on a single medium or may be split across two or more media. For example, some of the instructions may be written on a paper document that instructs a user to access one or more of the method steps via the Internet, and the Internet-accessible steps are stored on one or more computer-readable media.

[0085] Each of the additional figures and methods disclosed herein may be used separately or in combination with other features and methods to provide improved devices and methods of making and using the same. Thus, the combinations of features and methods disclosed herein are not necessarily required to practice the disclosure in its broadest sense, but are instead disclosed only to specifically illustrate representative and preferred embodiments.

[0086] Various modifications to the embodiments may be apparent to those skilled in the art upon reading this disclosure. For example, those skilled in the art will recognize that various features described in different embodiments can be combined, decombined, and recombined with other features alone or in different combinations as appropriate. Similarly, all of the various features described above should be considered as example embodiments rather than limitations on the scope or spirit of the disclosure.

[0087] Those skilled in the art will recognize that various embodiments may include fewer features than shown in any individual embodiment described above. The embodiments described herein are not intended to be an exhaustive representation of the ways in which various features can be combined. Thus, the embodiments are not mutually exclusive combinations of features, but rather, the claims may include combinations of different individual features selected from different individual embodiments, as would be understood by one of skill in the art.

[0088] The following publications are incorporated by reference in their entirety: Topolnjak et al., "Image-guided radiotherapy for left-sided breast cancer patients: geometrical uncertainty of the heart", International Journal of Radiation Oncology * Biology *Physics,82(4),e647-e655(2012);Kincaid Jr et al.,"Investigation of gated cone-beam CT to reduce respiratory motion blurring",Medical physics,40(4),041717(2013);Nankali et al.,"Geometric and dosimetric comparison of four intrafraction motion adaptation strategies for stereotactic liver radiotherapy",Physics in Medicine&Biology,63(14),145010(2018);Fayad et al.,"Correlation of respiratory motion between external patient surface and internal anatomical landmarks",Medical physics,38(6Part1),3157-3164(2011);Robinson et al.,"An evaluation of the Clarity 3D ultrasound system for prostate localization",Journal of applied clinical medical physics,13(4),100-112(2012);De Luca et al.,"The 2014 liver ultrasound tracking benchmark",Physics in Medicine&Biology,60(14),5571(2015);Lachaine et al.,"Intrafractional prostate motion management with the Clarity Autoscan system",Medical physics international,1(2013);Ipsen et al.,"Target tracking accuracy and latency with different 4D ultrasound systems-a robotic phantom study",Current Directions in Biomedical Engineering,6(1)(2020);Queiros et al.,"Fast left ventricle tracking using localized anatomical affine optical flow",International journal for numerical methods in biomedical engineering,33(11),e2871(2017);Roujol et al.,"Characterization of respiratory and cardiac motion from electro-anatomical mapping data for improved fusion of MRI to left ventricular electrograms",PloS one,8(11),e78852(2013);Baker et al.,"Prostate displacement during transabdominal ultrasound image-guided radiotherapy assessed by real-time four-dimensional transperineal monitoring",Acta Oncologica,54(9),1508-1514(2015);Khalil et al.,"An Overview on Image Registration Techniques for Cardiac Diagnosis and Treatment",Cardiology research and practice,2018(2018);Che et al.,"Ultrasound registration:A review",Methods,115,128-143(2017);Hoogeman et al.,"Clinical accuracy of the respiratory tumor tracking system of the cyberknife:assessment by analysis of log files",International Journal of Radiation Oncology. * Biology *Physics,74(1),297-303(2009);Depuydt et al.,"Treating patients with real-time tumor tracking using the Vero gimbaled linac system:implementation and first review",Radiotherapy and Oncology,112(3),343-351(2014);Keall et al.,"The management of respiratory motion in radiation oncology report of AAPM Task Group 76a"(2006);Blanck et al.,"Radiosurgery for ventricular tachycardia:preclinical and clinical evidence and study design for a German multi-center multi-platform feasibility trial(RAVENTA)",Clin Res Cardiol 109,1319-1332(2020);Zei et al.,"Ablative Radiotherapy as a Noninvasive Alternative to Catheter Ablation for Cardiac Arrhythmias"Curr Cardiol Rep(2017);van der Ree et al.,"Cardiac Radioablation-a Systematic Review",Heart Rhythm(2020);Graeff et al.,"Noninvasive cardiac arrhythmia ablation with particle beams",Med Phys 45(11)(2018);O'Shea et al.,"Review of ultrasound image guidance in external beam radiotherapy part II:intra-fraction motion management and novel applications",Physics in Medicine&Biology,v61(8)(2016);Fontanarosa et al.,"Review of ultrasound image guidance in external beam radiotherapy:I.Treatment planning and inter-fraction motion management",Physics in Medicine&Biology,v60(3),R77(2015);Bertholet et al.,"Real-time intrafraction motion monitoring in external beam radiotherapy",Physics in Medicine 64(15)(2019);Ipsen,"See what you treat:4d ultrasound imaging for real time motion compensation in the liver",PhD Thesis University of Luebeck(2019);Ipsen et al,"Radiotherapy beyond cancer:Target localization in real-time MRI and treatment planning for cardiac radiosurgery",Med Phys 41(12)(2014);Poon et al.,"Technical Note:Cardiac synchronized volumetric modulated arc therapy for stereotactic arrhythmia radioablation - Proof of principle",Med Phys 47(8)2020。.

[0089] Any incorporation by reference of a document herein is limited so that no incorporation to the contrary is made with respect to any express disclosure herein. Any incorporation by reference of such a document is further limited so that no claims contained in the document are incorporated by reference herein. Any incorporation by reference of such a document is further limited so that no definitions provided in the document are incorporated by reference herein, unless expressly included herein.

[0090] Unless otherwise noted, references contained in this specification to "embodiments," "disclosures," "the disclosure," "embodiments of the disclosure," "disclosed embodiments," and the like, refer to the specification (including the claims and figures) of this patent application, which are not admitted prior art.

[0091] For purposes of interpreting the claims, it is expressly intended that the provisions of 35 U.S.C. 112(f) not be invoked unless the specific terms "means for" or "step for" are recited in each claim.

Claims

1. 1. A method for locating a cardiac structure in a known three-dimensional coordinate system, comprising: providing a multi-planar imaging probe and a localization system for tracking said multi-planar imaging probe in three-dimensional space; Providing instructions in a tangible, non-transitory medium the instructions comprising: acquiring a first sequence of multiplanar images of the heart with the multiplanar imaging probe for a duration of at least one heart beat with the heart in a first position for each multiplanar image of the first sequence; During the step of acquiring the first sequence, localizing the multi-planar imaging probe using the localization system to define a first set of room coordinates at the first set of locations; acquiring a second sequence of multiplanar images of the heart with the multiplanar imaging probe for a duration of at least one heart beat with the heart in a second position for each multiplanar image of the second sequence; During the step of acquiring the second sequence, localizing the multi-planar imaging probe using the localization system to define a second set of room coordinates at the second set of locations; identifying a first representative set of multi-planar images from the first sequence of multi-planar images and a second representative set of multi-planar images from the second sequence of multi-planar images, the first representative set of multi-planar images and the second representative set of multi-planar images corresponding to known combinations of at least one of cardiac and respiratory motion phases; aligning the second set of room coordinates with the first set of room coordinates; determining translational and rotational displacements of the second representative set of multi-planar images relative to the first representative set of multi-planar images within the aligned first and second sets of room coordinates; A method comprising:

2. The method of claim 1 , wherein the known combination of cardiac and respiratory motion phases in the identifying step corresponds to the respiratory motion phase.

3. The method of claim 1 , wherein the instructions in the step of providing instructions include displacing a subject support in accordance with the translational and rotational displacements.

4. 2. The method of claim 1, wherein the instructions in the step of providing instructions include instructing the subject to hold their breath for at least one cardiac cycle to achieve the known respiratory state during the step of acquiring the first sequence of multiplanar images.

5. The method of claim 1 , wherein the step of acquiring the first sequence of multiplanar images of the instructions is performed in a respiratory phase.

6. A method for enabling and gating a beam, comprising the steps of: Coupling a multiplanar imaging probe and a probe localization system to a gating controller the gating controller includes a set of instructions for execution in real time on a non-transitory computer readable medium, the instructions comprising: (a) acquiring a series of reference multiplanar images of a beating heart within a subject using a multiplanar imaging probe; (b) during step (a), obtaining a reference position of the imaging probe for each of the reference multi-planar images of the series of reference multi-planar images; (c) identifying a cardiac phase for each reference multiplanar image of the series of reference multiplanar images; (d) acquiring live multiplanar images using the multiplanar imaging probe; and (e) during step (d), acquiring a live position of said multi-planar imaging probe; (f) identifying a cardiac phase of the live multiplanar image; and (g) performing a rigid body registration of the live multi-planar images and the live positions to corresponding reference images of the reference series of multi-planar images and corresponding reference positions associated with the corresponding reference images, the corresponding reference images representing the cardiac phases of the live multi-planar images, the rigid body registration providing a live cardiac position of the beating heart relative to a three-dimensional coordinate system to provide a live displacement of the beating heart relative to the reference positions; A method comprising:

7. The method of claim 6 , wherein the instructions to the gating controller include generating a status condition based on a comparison of the displacement to a predetermined threshold.

8. The method of claim 7 , comprising configuring the non-transitory computer-readable medium with the instructions.

9. A method for estimating cardiac displacement, comprising: (a) acquiring a series of reference multiplanar images of a beating heart within a subject using a multiplanar imaging probe; (b) during step (a), obtaining a reference position of the imaging probe for each of the reference multi-planar images of the series of reference multi-planar images; (c) identifying a cardiac phase for each reference multiplanar image of the series of reference multiplanar images; (d) acquiring live multiplanar images using the multiplanar imaging probe; and (e) during step (d), acquiring a live position of said multi-planar imaging probe; (f) identifying a cardiac phase of the live multiplanar image; and (g) performing a rigid body registration of the live multi-planar images and the live positions to corresponding reference images of the reference series of multi-planar images and corresponding reference positions associated with the corresponding reference images, the corresponding reference images representing the cardiac phases of the live multi-planar images, the rigid body registration providing a live cardiac position of the beating heart relative to a three-dimensional coordinate system to provide a live displacement of the beating heart relative to the reference positions; The method includes:

10. The method of claim 9 including generating a status condition based on a comparison of the displacement to a predetermined threshold.

11. 10. The method of claim 9, comprising affixing the multiplanar imaging probe to the subject's chest for use during performance of a reference simulation.

12. The method of claim 9, comprising fixing the multiplanar imaging probe to the subject's chest for use during performance of the steps.

13. 10. The method of claim 9, comprising instructing the subject to hold their breath for at least one cardiac cycle to achieve a known respiratory state.

14. The method of claim 9 , wherein the known respiratory state is end-expiratory breathing phase.

15. The method of claim 9 , wherein the reference series of multiplanar images is acquired at the beginning of a process.

16. The method of claim 9 , wherein the reference series of multiplanar images is acquired during a pre-stage simulation stage.

17. 1. A multi-planar motion management system for non-invasive cardiac ablation, comprising: A multi-planar imaging probe configured to acquire live multi-planar images within a probe volume, the multi-planar images being non-parallel; a probe localization system configured to acquire position data of said multi-planar imaging probe; an input / output (I / O) management system configured to simultaneously receive the live multiplanar images and the position data, and to establish an acquisition time of the multiplanar images and the position data; A gating system configured to receive and process the live multi-planar images, the position data, and the acquisition time, the gating system including a processor. wherein the processor comprises: identifying a cardiac phase corresponding to the live multiplanar image; defining from said position data a set of room coordinates that most closely corresponds in time to said live multi-sectional image; performing a rigid body registration of the live multiplanar image to a reference multiplanar image, the reference multiplanar image representing the cardiac phase; A multi-planar motion management system configured to:

18. a heart rate detection system for generating cardiac cycle data; the heart rate sensing system is configured to generate a trigger signal based on the cardiac cycle data; the I / O management system is configured to receive the trigger signal contemporaneously with the multi-planar image and the position data, and generate trigger signal information including an acquisition time corresponding to the trigger signal; and The multi-planar motion management system of claim 17 , wherein the gating system is configured to receive and process the trigger signal information to identify the start of a cardiac cycle.

19. 20. The multiplanar motion management system of claim 18, wherein the gating system is configured to utilize the trigger signal information to ascertain the cardiac phase.

20. 20. The multi-planar motion management system of claim 18, wherein the heart rate sensing system is an electrocardiogram (ECG) system, and the cardiac cycle data is generated from an electrocardiogram signal.

21. The multi-planar motion management system of claim 17 , wherein the position data is relative to a room coordinate system.

22. The multiplanar motion management system of claim 17 , wherein the live multiplanar images and the reference multiplanar images are of the same data type.

23. The multi-planar motion management system of claim 17 , wherein the position data identifies a position and orientation of the multi-planar imaging probe in three-dimensional space.

24. The multi-planar motion management system of claim 17 , wherein the multi-planar imaging probe is configured to simultaneously acquire the multi-planar images.

25. The multiplanar motion management system of claim 17 , wherein the multiplanar imaging probe includes a shape configured for attachment to a patient's chest.

26. The multiplanar motion management system of claim 17, wherein the multiplanar imaging probe acquires the multiplanar images at a rate in the range of 20 Hz to 50 Hz, inclusive.

27. The multiplanar motion management system of any one of claims 17 to 26, wherein the multiplanar imaging probe is a multiplanar ultrasound probe and the reference multiplanar image is an ultrasound image.

28. A treatment system for irradiating a target tissue for use in conjunction with a prior related data set, comprising: a multi-planar ultrasound probe for generating a series of time-lapse images of the target tissue along intersecting planes; a probe holder for removably fixing the multi-planar ultrasound probe to an external surface of a patient's chest, the probe holder having a plurality of reference markers for indicating a position and an orientation of the multi-planar ultrasound probe; a location system that provides position data over time of the multi-planar ultrasound probe relative to a fixed location within a treatment room; an ECG system providing cardiac phase data over time; a data management system configured to store and correlate the time-lapse images, the time-lapse location data, and the time-lapse cardiac phase data as a function of time to generate a related procedure data set, and configured to record the related procedure data set to the previous related data set to generate a recorded related data set; a computer coupled to the data management system and configured to receive as input coordinates of the target tissue relative to the fixed location within the treatment room; a gating system operably connected to the data management system and the radiation therapy system, whereby the gating system is configured to control irradiation of the target tissue based on at least one of the recorded related data sets and a cardiac phase gating signal; A treatment system comprising:

29. The system of claim 28, wherein the positioning system assists in orienting the patient relative to the fixed position.

30. The system described in claim 28, wherein the gating system controls irradiation of the target tissue based on at least one of a cardiac phase gating window and a respiratory gating window.

31. The system described in claim 30, wherein the data management system receives the cardiac phase gating window or the respiratory gating window as input.

32. The system of claim 28, wherein the data management system registers the associated treatment dataset to the previously associated dataset using rigid body registration.

33. The system of claim 30, wherein the respiratory gating window identifies a range of cardiac displacement or a portion of a respiratory cycle during which the target tissue is irradiated.

34. The system described in claim 28, wherein the probe holder holds the multi-planar ultrasound probe in contact with an outer surface of the patient's chest.

35. The system of claim 28, wherein the prior related dataset is a related simulation dataset.

Images