Methods for enhanced fusion image annotation

Abstract

Fluoroscopic imaging of a patient's heart involves positioning the patient in a sterile field and capturing a two-dimensional image or two orthogonal two-dimensional images using an X-ray fluoroscopy system. At least one of the two-dimensional images is displayed simultaneously on an operative display within or adjacent to the sterile field and on a remote image processor outside the field. The remote display two-dimensional image is registered to the iso-centered fluoroscopic image using high-contrast blood pool images. Once registered, a fluoroscopically opaque marker on the patient is annotated on at least one orthogonal fusion image to maintain registration or rapidly restore re-registration if the patient or fluoroscopy table moves. The overlay image may be manually marked or annotated to show anatomical or treatment information before, during, and after treatment, which may be simultaneously shown on the operative display.

Description

METHODS FOR ENHANCED FUSION IMAGE ANNOTATIONCLAIM OF PRIORITY

[0001] This application claims priority to U.S. provisional patent application no.63 / 771,926, titled “METHODS FOR ENHANCED FUSION IMAGE ANNOTATION,” and filed on March 14, 2025, herein incorporated by reference in its entirety.BACKGROUND

[0002] Imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), and echocardiography, are used in cardiovascular diagnostic applications. These imaging modalities may be fused to X-ray fluoroscopy using custom software to register and overlay the MRI, CT or echocardiography-derived two-dimensional (2D) and three-dimensional (3D) images of a heart to display the endocardium, epicardium, infarct and other regions and / or data of interest onto a live X-ray fluoroscopy image.

[0003] Cardiovascular disease is a leading cause of death in industrialized nations and the number one cause of death in the United States. More than 7.9 million American adults have suffered a myocardial infarction (MI), with 1.1 million new or recurring MI cases each year. MI is characterized by restricted blood flow resulting in oxygen starvation and eventual large-scale loss of cardiac muscle, which cannot spontaneously regenerate, ultimately leading to heart failure. Current existing treatments for restoring heart function after myocardial injury are so far limited to a strict medication regimen and cardiac transplantation as a last resort. However, demand far exceeds supply of healthy donor hearts, leaving the cardiovascular community to strive towards novel promising therapeutic strategies including tissue engineering, gene therapy and cell therapy. Recent clinical trials have tested different types of stem cells, genes and growth factors using several delivery routes such as intramyocardial injection including both epicardial and transendocardial injections, intracoronary infusion, intravenous infusion and retrograde delivery. However, it has been shown that intramyocardial transendocardial injections while being minimally invasive, also have improved acute retention compared to the other delivery routes. This improved retention in transendocardial delivery leads to a strong potential for treatment for tissue regeneration and functional recovery and has been shown to slow down and eventually reverse adverse remodeling after a myocardial infarction. In recent MI patients, the infarct zone may be very fragile and intramyocardial injections in the infarct zone or the border zones of the infarct may have increased risks of perforation and pericardia! effusion, which may lead to cardiac tamponade, a life-threatening event. In 1SG Docket No. 14990-701.600these cases, accurate site targeting and injection of biotherapeutic agents is critical to the safety of the patient.

[0004] In conventional cardiovascular catheterization procedures, X-ray fluoroscopy is typically used to assist the interventional cardiologist in guiding catheters such as a balloon catheter to the occluded artery in the heart during angioplasty; or in guiding catheters with a miniature grasping device at the end during cardiac biopsies; or in guiding a percutaneous injection catheter to and within the myocardium for transendocardial injections of biotherapeutic agents such as cells, genes, oligonucleotides, exosomes, biopolymers, peptides, proteins (e.g., growth factors and chemoattractants). Consequently, the catheters employed in cardiovascular catheterization procedures are designed to be X-ray visible so that they can be clearly seen and tracked during the procedure. However, there are a few disadvantages of using only X-ray fluoroscopy for more complex procedures such as transendocardial injections and His-Purkinje conduction system (HPS) pacing, and these disadvantages can have significant impact on catheter guidance and image interpretation. X-ray imaging is a projection imaging modality and typically two orthogonal views, Right Anterior Oblique (RAO) and Left Anterior Oblique (LAO), that may be useful to get an accurate sense of the location and orientation of the catheters in the heart in three-dimensional (3D) space. Because two views are required, if the catheterization suite is equipped with a single plane X-ray fluoroscopy system, then the X-ray C-arm needs to be constantly rotated between these two views throughout the procedure to obtain the projections needed to provide proper guidance of the transendocardial catheters to selected intramyocardial target injection sites. While X-ray imaging provides excellent device visualization, it offers little insight in cardiac tissue visualization. X-ray fluoroscopy does not distinguish healthy tissue from infarct tissue or tissue in the infarct border zone region nor does it provide a 3D anatomical and topographical view of the patient's heart. This may be especially important to the interventional cardiologist who, depending on the therapy of choice, is attempting to accurately target healthy tissue, infarcted tissue, infarct border zone tissue, or a combination thereof, for intramyocardial injections of biotherapeutic agents. For these reasons, image fusion systems that can combine X-ray fluoroscopy with anatomical and functional 3D models reconstructed from magnetic resonance (MR) or computed tomography (CT) images, thereby providing real-time information and visualization of the catheters, are of particular interest for these applications.

[0005] Magnetic resonance imaging (MRI) is the most accurate diagnostic imaging modality which can provide a high-quality 3D anatomical and functional roadmap of a 2SG Docket No.: 14990-701.600patient's heart and it is therefore commonly used with X-ray fluoroscopy in these fusion imaging systems. Cardiac MRI segments from which cardiac images can be reconstructed are obtained with excellent tissue contrast. These cardiac images allow accurate and efficient differentiation between healthy tissue, infarcted tissue, and infarct border zone tissue. However, most catheters and other cardiac devices, while safe to use and visualize with X-ray fluoroscopy, are not entirely compatible with MRI. Most of these devices contain ferromagnetic materials that can result in imaging artifacts and may be a safety hazard to the patient exposed to a strong magnetic field during MRI. Further, even with the most sophisticated techniques and instruments available, capturing MRI images can still take between fifteen to sixty minutes depending on the types of images being acquired and the MRI sequence being run. Therefore, MRI scans are typically performed prior to the interventional procedures. Cardiac images reconstructed from these scanned segments can be used concurrently with X-ray fluoroscopy to guide interventional cardiologists during transendocardial procedures to accurately and safely target regions of healthy, infarct and / or infarct border zone tissue, whether for injection of biotherapeutic agents or sampling of cardiac tissue.

[0006] Methods and systems for fusing pre-operative images and information on realtime fluoroscopic images are described in U.S. Patent No. 6,466,813; in U.S. Patent Publication Nos. 2008 / 0043901; 2011 / 0087088; and 2011 / 0087110; and in Tomkowiak et al. (2011) Catheterization and Cardiovascular Interventions 78:468-478. See also, U.S. Patent Nos. 7,848,553; 11,357,463; U.S. Publication No. 2013 / 0102890; and U.S. Patent Application No. 17 / 357,649.

[0007] The subject matter of the present application is related to that of U.S. Patent Application No. 17 / 357,649, filed lun. 24, 2021, which is a continuation of U.S. Patent No.11,357,463, filed uly 7, 2015, which is a continuation of International Patent Application No. PCT / US2014 / 010732, filed lanuary 8, 2014, which claims priority to Provisional Application No. 61 / 750,226, filed anuary 8, 2013; Provisional Application No. 61 / 750,233, filed anuary 8, 2013; and Provisional Application No. 61 / 750,237, filed anuary 8, 2013, the entire contents of which are incorporated herein by reference.SUMMARY OF THE DISCLOSURE

[0008] The present disclosure relates generally to imaging modalities and more particularly to methods and systems for fluoroscopic imaging of an anatomy and remotely annotating the image to show additional image or other information useful during surgery.

[0009] Recognized herein is a need for improved systems, and methods to facilitate the 3SG Docket No.: 14990-701.600registration, re-registration, and annotation performed using X-ray fluoroscopy with magnetic resonance imaging (MRI) or computed tomography (CT) imaging fusion during a procedure of transendocardial delivery, cardiac biopsy, and His-Purkinje conduction system (HPS) pacing by using transendocardial injection catheters, cardiac biopsy catheters, and pacing electrodes. Transendocardial delivery, cardiac biopsy, and HPS conduction system pacing may be enabled by steerable introducer catheters, and the pacing leads may use a splitable or peelable sheath to enable them to be left implanted.

[0010] Transendocardial delivery of agents may benefit patients suffering from cardiovascular disease including, but not limited to, chronic myocardial ischemia, acute myocardial infarction, chronic heart failure comprising ischemic and nonischemic heart failure, dilated cardiomyopathy, cardiac transplantation, amyloidosis, cardiac arrhythmias, and genetic diseases of the heart. For example, BioCardia's Helix Transendocardial Biotherapeutic Delivery System is a catheter platform in clinical use.

[0011] Biotherapeutics delivery may include cell therapies, gene therapies, mRNA, exosomes, protein and peptide therapeutics, and small molecule pharmaceuticals. Injectables delivery may include synthetic polymers, natural biopolymers, microparticles from about 15 pm to about 150 pm.

[0012] A cardiac biopsy, also known as an endomyocardial biopsy (EMB), may be performed to obtain a small sample of heart muscle tissue for examination in a lab, primarily to diagnose the cause of heart muscle problems (e.g., cardiomyopathy), assess the severity of heart failure, or check for signs of organ rejection after a heart transplant. A cardiac biopsy can also help diagnose conditions such as myocarditis (e.g., inflammation of the heart muscle), cardiac amyloidosis, or heart cancer. Cardiac biopsy may be performed with standard endomyocardial biopsy devices, for example, the JAWS device available from Argon Medical Devices Inc. of Plano, TX. These devices can be navigated within the heart using, for example, the Morph steerable introducer platform available from BioCardia, Inc. of Sunnyvale, CA

[0013] The present disclosure can also be used to record, select, and target sampling sites for heart biopsy procedures testing for immune rejection in patients undergoing or having undergone a heart transplant; in patients showing signs of cardiomyopathy, cardiac amyloidosis and myocarditis; or in patients whose heart cells are being harvested for other therapeutic or diagnostic purposes.

[0014] Fluoroscopic imaging of a patient's heart can be performed by positioning a patient in a sterile field and imaging the heart using an X-ray fluoroscopy system within the sterile field to produce a two-dimensional image. The two-dimensional image can be4SG Docket No.: 14990-701.600simultaneously displayed on an operative display within or adjacent the sterile field and on a display of a remote image processor outside the operative field. The two-dimensional image of the remote display can be manually marked or annotated to show anatomical or treatment information which is simultaneously shown on the operative display.

[0015] In some embodiments, a 3D image (e.g., MRI or CT) may be registered and aligned with at last one and typically at least two orthogonal 2D fluoroscopy images.Registration of the three-dimensional MRI or CT image with the orthogonal fluoroscopic images can be performed by projecting the MRI or CT image in the planes aligned with the two orthogonal images. The orthogonal fluoroscopic images may be iso-centered fluoroscopic images. A C-ARM X-ray system can be used to generate the orthogonal fluoroscopy images. The orthogonal fluoroscopy images can be taken by centering both the orthogonal fluoroscopy views so that the C-ARM of the X-ray system can be moved without moving the table holding the patient or changing the magnification so that registration MRI or CT images can be maintained in both views. A contrast (e.g., a radio-opaque contrast) can be injected into the patient's heart to enhance image contrast before, during, or after a procedure. In some embodiments, a radio-opaque contract can be injected into a patient's heart in an angiogram procedure (e.g., a ventricular angiogram), and the sharp contrast image can be used to fuse with the blood pool volume on the respective MRI or CT orthogonal projections. In some embodiments, the blood pool volume is taken at maximum diastole. The blood pool can be used to fuse the images to provide for superior image resolution and alignment of the two imaging modalities. In some embodiments, the blood pool may be used as a shared reference point or points to guide image fusion. The preferred timing of fusing of the images for transendocardial delivery may be during diastole when the heart volume is largest and during expiration.

[0016] Enabling re-registration in instances when the table or patient move may also be important. One or more radio-opaque markers in the X-Ray image field can be near the patient's chest or back which appears on the live fluoroscopy image and can be marked on the MRI or CT image projections. At least one such marker can be included, with two orthogonal markers can be included preferred. A marker such as an adhesive electrocardiogram electrode patch attached to the patient, or a forceps clipped to the drape in the imaging field can be sufficient for rapid realignment of the image registration.

[0017] One or more of the 2D images, 3D images, or fused images may be manually marked by one or more users. Manually marking the image may comprise manipulating a graphical user interface on the remote image processor, and the graphical user interface may comprise a touchscreen, a mouse, a roller ball, or a joystick. Manually marking the two- 5SG Docket No.: 14990-701.600dimensional image may comprise marking any one or more of an outline of the heart or portions thereof, target treatment regions, regions to avoid treating, and the like. Further, the regions treated can be annotated after the physician treats each location, such as with an alpha numeric representation. A single point annotation may use two annotations in the two orthogonal views to define its location in three-dimensional space. In some embodiments, the manual marking and / or annotation may be performed pre-operative with the 3D image or intra-operative with the 2D or 3D or fusion image.

[0018] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.INCORPORATION BY REFERENCE

[0019] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material.BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the present disclosure are utilized, and the accompanying drawings (also "figure" and "FIG." herein), of which:

[0021] FIG. 1 shows an example of method of combining imaging modalities as described herein. In FIG. 1, recordings of left ventricular contours and target sites are shown in two dimensions (2D), in a single orthogonal view. Recordings are performed in orthogonal views and input from the assessment of other image results (such as MRI, CT, ECHO and PET may be used).

[0022] FIGS. 2A-2D schematically illustrate an example of a method including6SG Docket No.: 14990-701.600recording a target site on a 2D image.

[0023] FIG. 3 schematically illustrates an example of a method of recording of target sites on 2D / 3D images.

[0024] FIG. 4 shows an example of a method of indicating treatment (e.g., injection) sites using the apparatus and techniques described herein.

[0025] FIG. 5 schematically illustrates an example including a method of recording target sites on 2D / 3D images.

[0026] FIGS. 6A-6B shows right anterior oblique (30 degree) and left anterior oblique (60 degree) images. FIGS. 6C-6D illustrate examples of presumptive locations of electrophysiologically relevant and anatomic structures in a typical heart.

[0027] FIGS. 7A-7B illustrates examples of bullseye views that may be included with any of the methods and apparatuses described herein.

[0028] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive surface area.DETAILED DESCRIPTION

[0029] While various embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the present disclosure. It can be understood that various alternatives to the embodiments of the present disclosure described herein may be employed.

[0030] Whenever the term "at least," "greater than," or "greater than or equal to" precedes the first numerical value in a series of two or more numerical values, the term "at least," "greater than" or "greater than or equal to" applies to each of the numerical values in that series of numerical values. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

[0031] Whenever the term "no more than," "less than," or "less than or equal to" precedes the first numerical value in a series of two or more numerical values, the term "no more than," "less than," or "less than or equal to" applies to each of the numerical values in 7SG Docket No.: 14990-701.600that series of numerical values. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

[0032] As used herein and in the appended claims, the singular forms "a," "and," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an agent" includes a plurality of such agents, and reference to "the cell" includes reference to one or more cells (or to a plurality of cells) and equivalents thereof known to those skilled in the art, and so forth. When ranges are used herein for physical properties, such as molecular weight, or chemical properties, such as chemical formulae, all combinations and sub combinations of ranges and specific embodiments therein are intended to be included. The term "about" or "approximately" when referring to a number or a numerical range may refer that the number or numerical range referred to is an approximation within experimental variability (or within statistical experimental error), and thus the number or numerical range may vary between 1% and 15% of the stated number or numerical range. The term "comprising" (and related terms such as "comprise" or "comprises" or "having" or "including") is not intended to exclude that in other certain embodiments, for example, an embodiment of any method, or process, or the like, described herein, may "consist of or "consist essentially of the described features.

[0033] Recognized herein is a need for improved systems, and methods to facilitate the registration, re-registration, and annotation performed using X-ray fluoroscopy with magnetic resonance imaging (MRI) or computed tomography (CT) imaging fusion during a procedure of transendocardial delivery, cardiac biopsy, and His-Purkinje conduction system (HPS) pacing. The present disclosure provides apparatuses (e.g., systems, devices, etc.) and methods for combining a 3D model reconstruction of the heart derived from MRI performed prior to an interventional procedure with live X-ray fluoroscopy images during a catheterization procedure (e.g., in real time or near real time) to assist in a procedure within the myocardium, including but not limited to facilitating catheter guidance, placement of one or more devices and / or delivery of a therapeutic material or apparatus. Thus, these methods and apparatuses may improve the safety and accuracy of procedures including transcatheter injections of biological and chemical therapeutic agents in the diseased heart.

[0034] In general, the methods and apparatuses described herein may use MRI data specific to the patient to be treated. Cardiac MRI slices, detailing the endocardial and epicardial surfaces of the heart and the infarct regions in the heart, can be acquired during MRI scans. Commercially available platform-independent contouring packages or other freeware such as Segment (Medviso), The Visualization Toolkit (Kitware, Inc.), QMass® MR Enterprise Solution (Medis medical imaging systems, Inc.), can be used to define the 8SG Docket No.: 14990-701.600endocardial and epicardial walls and the infarct for each slice and thus, generate a 3D model of the patient's heart prospectively to the interventional procedure. Custom automation may be performed and may be performed remotely from the clinical site in a cloud computing environment. Other imaging modalities (e.g., CT, echocardiography) that can define the anatomical and functional details of the heart, and from which a 3D model can be reconstructed, can also be used in place of an MRI. The output format from the contouring packages can conform to the X-ray fluoroscopy system. Prior to a procedure, the 3D space within the field of view of the fluoroscopy system can be virtually created within the apparatuses (e.g., fusion imaging systems) described herein. During the interventional procedure, a ventriculogram can be taken of the patient's left ventricle in two orthogonal views. The 3D model created from the MRI scan can be virtually placed into a 3D space and registered by translational, rotational, and scaling of the virtual image projection to fit the ventriculograms of the X-ray fluoroscopy system in both orthogonal views. The 3D image can contain information specific to the electrophysiological domains within the heart and / or on physiological information; for example the information may include (but is not limited) to information on regions of myocardial infarction, wall thickness, and contraction properties of the heart. The multiple (e.g., two or more) orthogonal projections to be fused with the X-ray images can be used to define and display essential parameters and limitations central to the safe treatment of the patient. For example, in transendocardial intramyocardial injections of biotherapeutic agents into the patient's heart, important information such as the myocardial infarct location and size, differentiation between infarct zones if there is more than one, left ventricular wall thickness, hypokinetic and akinetic regions, target injection zones and 'Do not inject' zones (e.g., the papillary muscle, regions close to the mitral valve, the apex, the basal septal wall where the His bundle lies and thin regions of the myocardial wall) can be important data points for the safe treatment of the patient. These data points can be obtained from MRI segments or CT slices and using the software interface, can be translated within the 2D or 3D model of the heart prior to the interventional procedure, thereby creating an anatomical and functional roadmap of the heart. Based on the inclusion and exclusion criteria for intramyocardial injections in each study, specific regions can be traced and demarcated using different colors and / or patterns, thus, clearly displaying the selected target regions of interest and the Do not inject' zones to the interventional cardiologist.

[0035] Any of these methods and apparatuses may also allow and encourage the user to virtually mark a tool region (e.g., catheter tip) within the image to enhance tracking. Marking may be manual, automatic or semi-automatic (e.g., manually confirmed or adjusted after automatic detection is attempted).9SG Docket No.: 14990-701.600

[0036] In some embodiments for transendocardial delivery, the presentation of the myocardial infarct regions may be marked (e.g., colored, such as in yellow), and the thinner regions of the wall (e.g., 5 mm or less ventricular wall) may be marked (e.g., colored, e.g., in red). Regions around the infarct with wall thickness greater than 5 mm and about two to three centimeters wide can be annotated (e.g., colored, e.g., in green) identifying preferred zones for peri infarct delivery. Identification of the visual marker can be manually annotated before the procedure. During the procedure, the physician may select regions within the marked (e.g., green) target zone and perform deliveries. After each delivery, the location can be annotated in each orthogonal view based on the catheters position with the same alphanumeric symbol so that each marked location can have the same identifier in both views, but that each location has unique alphanumeric identifier.

[0037] The disclosure generally provides embodiments for fusion imaging systems with X-ray fluoroscopy, cardiac catheters, transendocardial injection catheters, pacing leads for CT or MRI facilitated left bundle branch pacing, left bundle branch area pacing, and HIS pacing, and methods of use to register and transpose multi-modality images to guide targeted procedures within the myocardium such as transendocardial deliveries and cardiac biopsies.EXAMPLESExample 1. Recording of Left Ventricle Contours and Target Sites on Screen- 2D

[0038] In one example, as shown in FIG. 1, a ventriculogram was performed to digitally outline the left ventricular contours of a patient's heart in diastole and systole by using a touchscreen, mouse, tablet or other graphical input device and displayed on a monitor of a separate computer or workstation in both orthogonal views in 2D space in a control room or in a designated area of the catheterization suite away from the X-ray fluoroscopy system and outside of the sterile zone. The computer workstation has an internal modem or network connection device which is in communication with the computer of the single plane X-ray fluoroscopy system via an intranet communications link system The communications link to the network can be any acceptable type, including, but not limited to, telephone lines, fiber optics, cable modem links, and wireless data transfer systems. The input and display on the monitor of the separate computer workstation were transmitted and outputted to the monitor of the single-plane X-ray fluoroscopy system, and vice versa. For transendocardial injections of biotherapeutic agents into the patient's hearts, information such as the myocardial infarct location, hypokinetic and akinetic regions, and 'Do not inject' zones as described elsewhere herein may be important to identify. Such information may be displayed on a monitor in the catheterization suite and can help guide the interventional cardiologist during surgical procedures. The display can be performed after mapping the left ventricle in the two10SG Docket No.: 14990-701.600orthogonal views and prior to the start of the transendocardial injection procedures. Based on the procedure and therapy requirements, the operator can mark the zones on the remote computer to define the areas where injections may and may not be made on the ventriculograms in both orthogonal views. The demarcations can be done, for example, by color coding, using solid and dashed lines, and / or using different shapes and patterns. As described elsewhere herein, the two orthogonal views may be helpful to verify the location and orientation of the percutaneous catheters in the left ventricle and to verify and mark an injection site. A function or key may be used to toggle between the annotated LV contour maps in the two orthogonal views on the remote computer and may be displayed on the monitor of the X-ray fluoroscopy system Toggling between the two LV contour maps can enable the operator to remotely mark up the target injection sites in each view without having to switch between transparencies secured to the monitor of the single plane X-ray fluoroscopy system in the catheterization suite. Marking of the injection sites can be done by digitally marking the location of the catheter tip during the transendocardial injection process. If the marking is iso-centered and the table is not moved, a single label can be valid in both views. Marks may be color coded, have varying shapes or sizes, and / or have any number of associated fields to record additional information. The site coloring or numbering can be subsequently displayed with adjustable level of transparency or hidden on the display. The displays may be grouped such that certain properties can be changed by the group instead of individually. A few parameters associated with the marked sites may further be displayed on the screen in a separate window. In the separate window, the operator can choose the parameters to appear next to the marked injection site by checking or unchecking checkboxes associated with the parameters. Examples of parameters may include: the injection site number, the total number of injections, the volume of therapeutic agent injected (e.g., from about 0.1 ml to about 1.0 ml per injection for intramyocardial injections), the dosage of therapeutic agent being delivered (e.g., concentration, total number of cells ranging from about 1 x 106 cells to about 200 x 106 cells, total amount of plasmid / gene or peptide or protein, total number of particles), a time stamp, screen coordinates, the ventricular wall thickness or electrophysiologic activity at that injection site, the segment injected based on a 17-segment bull's-eye map, the distance from the infarct location, the distance from other injection sites.

[0039] The same capabilities of the software may be available if a bi-plane X-ray fluoroscopy system is available in the catheterization suite. However, there may be no need to toggle from RAO view to LAO view since both views can be projected onto two separate screens mounted to the bi-plane X-ray system. In this example, the two projected11SG Docket No.: 14990-701.600fluoroscopic images may be independently input into the computer and subsequently output with the associated annotations as described elsewhere herein to either two independent displays or as two windows on a single display.

[0040] The software interface may also enable the 2D left ventricle image projections, the marked injection sites, and the parameters in either view can be toggled ON and OFF. Example 2. Preselected Target Sites

[0041] In another example, as shown in FIGS. 2A-2D, a method for selecting target points within the heart of a patient for injecting therapeutic agents in transendocardial intramyocardial interventions or for sampling tissue in biopsy procedures can be performed. In this example, the same procedure as described in Example 1 can be followed, and the target sites can be preselected either manually or by using various algorithms. These algorithms may be executed by a computer and may result in (1) a uniform equally distributed grid projection on the endocardial surface; (2) a uniform grid excluding the infarct zone and spaced at about Oto about 20 millimeters from the infarct zone; (3) a uniform grid within the infarct zone; (4) a uniform grid distally located and equally distributed within the distal third of the ventricle or the apical region of the left ventricle; (5) a uniformly distributed circular pattern or other functional geometric distributions that may be preferred. The target sites ranging in number from about 1 to about 20 may be preselected based on a set of parameters for the specific procedure. In addition to what is disclosed in Example 1, these parameters can further include distance from the infarct zone, wall thickness of at least about 5 millimeters, distance between injection sites (e.g., greater or equal to about 5 millimeters), equally spaced injection sites, randomly spaced injection sites from the infarct zone, randomly spaced injection sites at a defined distance from the infract zone, and can exclude previous sites of therapeutic delivery for transendocardial injections and previous sampling sites for cardiac biopsies. Diagnostic cardiac MRI scans, CT scans, and echocardiography may be used before the day of the procedure to determine required prespecified information, such as wall thickness and infarcted tissue location. On the day of the procedure, before the start of the procedure, a ventriculogram can be performed in both orthogonal views and the contours of the left ventricle mapped as described in Example 1. An algorithm selected from the list described above can then be executed by the computer and target sites can be pre-selected with the pre-defined parameters and can be displayed. Similar to Example 1, display of the preselected target points can be done by means of markers of different shapes, patterns and / or colors which can be toggled on and off, grouped or ungrouped. The tip of the penetrating element at the distal end of the transendocardial catheter or the guiding biopsy catheter can be moved to one of the preselected target points.12SG Docket No.: 14990-701.600Once the injection or sampling has been performed, the actual injection site can be marked at which point the preselected target point may be hidden or replaced. The marker for the actual injection or sampling marker may be of different shape, pattern and / or color than the target marker(s). The new marker can be saved and can be shaded or hidden before moving to the next preselected target point. If the actual target site differs from the preselected target site, an algorithm can be applied to readjust the rest of the preselected target sites based on the parameters forced on the pre-selection. The algorithm can be rerun after each injection / sampling is performed to adjust the preselected sites accordingly. Further, if the interventional cardiologist is not satisfied with the preselected target sites, the interventional cardiologist can indicate where he / she prefers the first site to be and that site can be registered by clicking on the new site position in both RAO and LAO views and the algorithm can be rerun to change the locations of the rest of the preselected target sites relative to the redefined first site.

[0042] Actual target sites within the left ventricle of a patient, where injection has been performed, can be registered, and saved. These target points can be displayed along with a series of parameters comprising the patient identification number, an injection number, a time stamp, the identity of the therapy injected, the volume injected at the injection site, the concentration injected, the total dosage injected, screen coordinates, the wall thickness and / or electrophysiologic activity at the injection sites, the distance from the infarct location to the injection sites, the distance from the nearest injection site, and the quality or character of contrast delivery from either the base of the penetrating element or through the distal penetrating element. In an example where sampling is performed, such as in right ventricular cardiac biopsy, the series of parameters can include previous records of where samples have been taken from a patient's heart including data related to the sample character, such as their rejection grade score. Including previous records can facilitate future sampling strategy and algorithm pre-selection as discussed elsewhere herein in Example 2. Additional parameters may include patient identification number, a sample number, a time stamp, a set of coordinates where the tissue is being sampled, the wall where the sample is taken, the segment of a standard 17-segment heart model bulls-eye plot where the sample is taken, the wall thickness at the sampling site, the distance of the sampling site from the infarct location, and the distance from the nearest sampling site if more than one sample is taken. In some cases, a sampling device or bioptome that includes the ability to deliver contrast either through a penetrating distal element in the tissue or a contrast port at the base of the biopsy element can enhance positioning and marking on the fusion image. In some cases, the electrophysiologic activity for a therapeutic delivery, biopsy, or pacing electrode implantation 13SG Docket No.: 14990-701.600at the site can be recorded with a catheter device that enables the recording of bipolar signals, to confirm the suitability of the site prior to delivery, biopsy, or pacing lead implantation or after delivery biopsy, or pacing lead implantation at the site to confirm the location.Example 3. Recording of Target Sites on Screen - 3D

[0043] In another example, as shown in FIG. 3, a method for selecting target points within the left or right ventricle of a patient to inject therapeutic agents in transendocardial intramyocardial interventions or to sample tissue in biopsy procedures can be performed. In this example, a 3D heart model reconstructed prior to an interventional procedure from cardiac slices obtained using an imaging modality capable of 3D visualization of cardiovascular structures (magnetic resonance imaging, computer tomography, echocardiography) can be combined with live X-ray fluoroscopy images during a catheterization procedure. After acquisition of the patient's ventriculogram, the 3D model reconstruction of the heart can be registered onto the orthogonal ventriculogram images and projected onto the live X-ray fluoroscopy images. This can create combined X-ray projection images with an overlay of the registered MR, CT or echocardiography images.

[0044] In this example, registration can be achieved by aligning at least two anatomical fiducial markers on the 3D reconstructed model with corresponding points on the ventriculograms in the two orthogonal views. Registration can also be achieved by aligning and scaling the 2D ventriculogram blood volumes in end diastole with the blood volume in the CT or MRI images in end diastole. The registration and subsequent steps in target point selection can be performed on a separate computer workstation in the control room or in a designated area of the catheterization suite away from the X-ray fluoroscopy system and the sterile zone, and in direct communication with the X-ray fluoroscopy system such that the resulting output can be displayed on the monitor of the fluoroscopy system or on separate monitors visible to the physicians. Target injection or sampling areas can be selected based on the inclusion and exclusion criteria of the procedures. For example, for transendocardial intramyocardial injections, criteria can include wall thickness of less or equal to about 5 millimeters, the location of the infarct, the size of the infarct, the distance from the infarct to the injection site and the basal section of the septal wall of the left ventricle, can be identified and marked along the 3D surface of the left ventricle on the remote computer and output onto the fluoroscopy monitor. In another example, in the case of tissue sampling for biopsy procedures, criteria can include the wall thickness, the location of the infarct, the size of the infarct and previous biopsy sampling sites can all be marked. These areas may be denoted by, for example, color coding, using solid and dashed lines, and / or using different shapes and patterns. These demarcations can allow the interventional cardiologist to view where he / she 14SG Docket No.: 14990-701.600may or may not inject therapies or sample tissue. During the procedure, the tip of the penetrating element at the distal end of the transendocardial injection catheter, or of the guiding biopsy catheter can be moved to a target point. Using visual recognition, the target point can be fixed in 2D space by means of a target marker on the monitor. The target marker can be overlapped onto the tip of the penetrating element in two orthogonal RAO and LAO views, wherein the target marker can be forced to travel in 3D space along the endocardium when it may be in target identification mode so that it is in the same 3D space as the tip of the penetrating element. Registration of the fixed target point and the target marker can be completed by means of markers which can take different shapes and can be color coded. In some cases, when the injection or sampling has been performed, registration of the actual injection point is done by replacing the target point marker with a marker having a different shape and / or color. The new marker can be saved and can be hidden or shaded before moving to the next target point.

[0045] As described elsewhere herein in Example 1, if a bi-plane X-ray fluoroscopy system is available in the catheterization suite, there may be no need to toggle from RAO view to LAO view since both views can be typically projected onto two separate screens for the bi-plane X-ray system.Example 4. Fitting 2D Heart Model onto X-Ray Fluoroscopy Images

[0046] In another example, as shown in FIG. 4, a method of fitting a 2D heart model onto left or right ventriculograms in both RAO and LAO views and subsequently, onto live X-ray fluoroscopy images can be performed. In this example, the same procedure and software capabilities as described in Example 2 may be followed. However, instead of fitting a 3D model of the left ventricular contours, data obtained from cardiac MRI, CT or echocardiography segments can be used to reconstruct a 2D model of the ventricle in the same plane as the fluoroscopic projection prior to the procedure, and the same regions of interest and parameters as described elsewhere herein can be marked onto the 2D model. The markings can be done primarily through color coding, the use of solid and dashed lines, and / or by the use of different shapes and patterns, which can be toggled on and off.Otherwise, the selection and registration of the target sites can be performed as described in Examples 1 and 2.

[0047] As described elsewhere herein in Examples 1 and 2, if a bi-plane X-ray fluoroscopy system is available in the catheterization suite, there may be no need to toggle from RAO view to LAO view since both views can be typically projected onto two separate screens mounted to the bi-plane X-ray system.15SG Docket No.: 14990-701.600Example 5. Selecting Target Points Within the Left Ventricle of a Patient

[0048] In another example, as shown in FIG. 5, a method for selecting target points within the left ventricle of a patient for injecting therapeutic agents in transendocardial intramyocardial interventions, or for sampling tissue in biopsy procedures with the help of multi-modal fusion imaging can be performed. In this example, the same procedure as described in Example 3 may be followed, with the exception that the target sites may be preselected using a computer algorithm. The computer algorithm may be programmed to choose the target sites ranging in number from about 1 to about 20 based on a set of parameters for the specific procedure. In addition to parameters described elsewhere herein in Example 3, additional parameters can include distance from the infarct zone, distance between injection sites (e.g., greater or equal to about 5 millimeters), equally spaced injection sites, randomly spaced injection sites from the infarct zone, randomly spaced injection sites at a defined distance from the infract zone, or pre-specified electrophysiologic activity. Prior to the start of the procedure, the target sites can be preselected using the algorithm with the predefined parameters and displayed by the software. As described in Example 3, the display of the preselected target points may be done by means of markers of different shapes, patterns and / or colors which can be toggled on and off. The tip of the penetrating element at the distal end of the transendocardial catheter or the guiding biopsy catheter can be moved to one of the preselected target points. In some cases, once the injection or sampling has been performed, the actual target point can be registered by replacing the marker marking the preselected target point with a new marker of different shape, pattern and / or color. The new marker can be saved and can be shaded or hidden before moving to the next preselected target point. An algorithm can be applied to readjust the rest of the preselected target sites based on the parameters forced on the pre-selection if the actual target site differs from the preselected target site. This algorithm can be rerun after each injection / sampling is performed to adjust the preselected sites accordingly. Further, if the interventional cardiologist is not satisfied with the preselected target sites, the interventional cardiologist can indicate where he / she prefers any target to be and that target can be registered by clicking on the new position in both RAO and LAO views and the algorithm can then be rerun to change the locations of the rest of the preselected target sites relative to the first.Example 6. Anatomic Fusion of Target Information for His-Purkinje Conduction System (HPS) Pacing

[0049] In another example, a method for providing information on the cardiac conduction system to cardiac electrophysiologists performing conduction system pacemaker implantation can be performed. Approaches for left bundle branch pacing (LBBP), left 16SG Docket No.: 14990-701.600bundle branch area pacing (LBBAP), a cardiac pacing technique that captures the left bundle branch of the heart, and His bundle pacing (HBP) are described herein as concepts of conduction system pacing or physiologic pacing. The anatomy and details are well described in Cardiac Conduction System Pacing: A Comprehensive Update, JACC: Clinical Electrophysiology, Volume 9, Issue 11, November 2023, the entire contents of which are incorporated herein by reference.

[0050] One challenge in precisely locating the electrode within the heart is accurately determining its position relative to smaller structures, confirming placement using the heart's electrical signals, and ensuring that pacing successfully depolarizes or captures the intended tissue.

[0051] In one example, a pacing lead can be placed deep in the septum of the heart, near the left bundle branch (LBB). The LBB can be captured, which can be confirmed by measuring the paced QRS morphology, peak left ventricular activation time, and other metrics. In some cases, LBBP can improve left ventricular ejection fraction, reduce the risk of death or hospitalization for heart failure, shorten the QRS complex duration, and correct left bundle branch block (LBBB). In some cases, LBBP can also be a better option than biventricular pacing for patients who need cardiac resynchronization therapy. In some cases, LBBP-optimized cardiac pacing can help patients with heart failure.

[0052] In some cases, patients may require a more distal pacing target, late increases in capture thresholds can occur, and there can be a learning curve for HPS pacing.

[0053] In this example, an MRI or CT image overlay can be scaled, rotated, and positioned to align the blood pool volumes, with preprocedural identification in the MRI or CT image of one or more of the regions of interest, such as, the heart valve anulus and conduction system elements, which can include Atrioventricular (AV) node, Sino Atrial (SA) node, HIS bundle, and bundle branches. The preprocedural CT scan can estimate these locations and a simulation of the anatomy can be made for the treating physician in the fluoroscopy overlay such as shown in FIG. 6, even if complete information is not available from the CT or MRI images.

[0054] In some cases, the treating physician can use the simulation to select the angle of attack and position the pacing lead to target the optimal zone for pacing. Pacing electrodes on the trunk of the HPS have also been shown to be superior compared to pacing the more distal fascicles.

[0055] One challenge in these procedures may be the concern among some electrophysiologists about potential damage to the valve structures, given the proximity of the HPS trunk to the valve. However, detecting a current of injury during lead implantation can 17SG Docket No.: 14990-701.600confirm the myocardial nature of the penetrated tissue, which can be observed from the pacing electrode.

[0056] In one embodiment, the physician can fuse the anatomy on CT or MRI scans taken from before the procedure, with visual enhancements to the structures of interest in their fused fluoroscopy images. For example, a valve annulus may be colored, and each element of the conduction system may be colored differently. During the procedure, the physician may place the pacing electrode, measure a current of an injury if the injury is near a valve structure of concern, assess the pacing capture, and assess the lowest voltage at which the system can successfully capture which can be confirmed by measuring the paced QRS morphology, peak left ventricular activation time and other metrics. If reposition is needed, the physician may mark both the site of the electrode and the vector of the distal end of the pacing electrode so they may know their angle of attack to guide their next attempt. The end of the final selected site can also be recorded. The targets annotations can be placed after the physician specifies them This technology is useful as a tool for the physician even as the field evolves with specific targeted pacing goals.

[0057] In this example, similar to examples described elsewhere herein for transendocardial delivery and biopsy procedures, a marker can be attached to the patient in case the fluoroscopy has to be repositioned mid procedure, and the blood pool volumes during ventricular angiography at maximal diastole can be fused.

[0058] As described in FIGS. 6A-6D, the fusion imaging can present information in image C imposed over image A and the information in image D imposed over image B to inform and guide the physician during the procedure.

[0059] In the examples described herein, target points within the heart of a patient, where injection has been performed, a biopsy has been taken, or pacing has been attempted or implanted can be registered and saved. These target points can be displayed with a series of parameters comprising of the patient identification number, an injection number, a biopsy or pacing implant attempt number, a time attempted, screen coordinates, the wall thickness at the injection sites, electrophysiologic activity, the pacing threshold, and whether capture was achieved as desired. For transendocardial delivery, parameters can include the distance from the infarct location to the injection sites, and the distance from the nearest injection site. In some cases where sampling or biopsy is performed, the series of parameters can include the patient identification number, a sample number, a time stamp, a set of coordinates where the tissue is being sampled, the wall where the sample is taken, the segment of a standard 17-segment heart model bulls-eye plot where the sample is taken, the wall thickness at the sampling site, electrophysiologic activity, the distance of the sampling site from the infarct 18SG Docket No.: 14990-701.600location, the distance from the nearest sampling site if more than one sample is taken.Bullseye views

[0060] Any of the methods and apparatuses described herein may include a bullseye display of the heart. Such a display may be particularly desirable to target peri-infarct zones. As used herein, a bullseye view or map may be from a craniocaudal view, e.g., as a polar projection that may be formed by stacking short-axis slices from base to the apex of the heart, then projecting them as concentric rings. For example, in some cases the bullseye map / view may be generated from the 3D views (e.g., a 3D model) of the heart, generated by, e.g., MRI or CT. In some examples the 3D view may be segmented (or alternatively unsegmented) and viewed down the craniocaudal axis. In some cases the bullseye view / image may be generated from stacked section through the 3D image (or model) of the heard transverse to the craniocaudal axis. In some cases the bullseye view may be a projection down the craniocaudal axis.

[0061] In general, the bullseye view is a top-down (craniocaudal) perspective onto the heart. These methods and apparatuses, including these bullseye mapping, may be useful for the identification of myocardial segments suitable for treatment, including implantation of a medical device and / or intramyocardial injection based on echocardiographic analysis of segmental wall thickness and wall contractility and the generation of a 2D Bull’s Eye cardiac map to visualize these myocardial target segments. Thus, the methods and apparatuses described herein may include the identification of potential myocardial segments based on echocardiographic data and visualization of this information in a bullseye map / view. Thus, any of these methods and apparatuses may include the identification of potential myocardial segments based on echocardiographic data and visualization of this information in a bullseye map.

[0062] As described above, when annotating each of the two orthogonal projections (e.g., LAO, RAO) that are fused to the 3D images results in these two points defining a point of intersection in the 3D fused image. This point can also be represented in the bullseye map projection of the three dimensional MRI or CT image. For example, if a catheter at position in the heart and markings are made indicating the tip of the catheter (e.g., of the tip of the catheter in each of the orthogonal images, e.g., LAO, RAO, this creates a point in 3D volume. This point can also appear on the bullseye flattened projection of the 3D volume.

[0063] The bullseye map view may also or alternatively help orient the physician in the other two views (e.g., orthogonal views and / or fused 2D / 3D view) and in some cases all of these views may be shown at the same time. In some cases the user interface may be configured to allow the user to toggle between the two orthogonal fluoroscopy 2D images (or 19SG Docket No.: 14990-701.600the 2D images and the fused 2D / 3D image), but the bullseye can remain in a view (e.g., in the comer of the 2D projection image).

[0064] In any of these methods and apparatuses, the bullseye view may be a simplified schematic (rather than photorealistic) representation of the heart, as shown in FIGS. 7A-7B. For example, the bullseye view may be a simplified schematic of the heart. The bullseye view may be dynamically linked to the other views, which may be shown concurrently with, and / or in some examples toggled between, the other images (2D and / or 3D), such as the fluoroscopic images, e.g., LAO and / or RAO, and may be dynamically updated, e.g., showing marker(s) added as described herein, as such markers are added to the 2D, 3D or 2D / 3D hybrid views described herein.

[0065] In general, a bullseye mapping may be dynamic, e.g., may show the position of the catheter tip in examples (as described above) in which the tip and / or treatment sites are being actively displayed, e.g., during a procedure. For example, a bullseye map may be used to show target regions (e.g., sites that are beneficial for implantation / inj ection, etc.) and / or for anatomic markers or data (e.g., wall thickness, high / low conduction regions, etc.). Examples of markings that may be made on a bullseye image / mapping may include contractility (wall motion) and / or wall thickness. In some cases the bullseye may be segmented into polar regions (e.g., in FIGS. 7A-7B, examples of bullseye mappings are shown divided into 17 segments arranged in a polar plot around a central region. Any number or regions of similar or different sizes may be used. Alternatively, the bullseye map / image may be continuous or semi-continuous.

[0066] In any of these cases the bullseye map / image may be marked (by color, text, etc.) to indicate a value for one or more parameter, including wall mobility / motion, wall thickness, etc. For example, FIG. 7A shows an example of a bullseye map / image in which the regions of the heart in the down in this top-down view are marked to indicate wall motion type, e.g., normal is shown darker (regions 10, 4, and 5), hypokinetic as lighter (regions 3, 9, 14, 15, and 17), akinetic (regions 1, 2, 6, 8, 7, 12, 13 and 16) and dyskinetic (none shown) may be indicated by other markers. Additional markings may also be shown overlaid or concurrent with this, including markings showing the target and / or delivered locations of an implant and / or injection, etc.

[0067] FIG. 7B shows an example of a bullseye map / image for the heart showing myocardial thickness. In this example, thickness ranges are shown by markings, e.g., wall thickness of less than 5 mm are shown by a first color marking (regions 1, 6, 7, 12, 13, 14, 16, and 17), regions having a thickness between 5-8 mm are indicated by a second color marking (regions 2, 3, 8, 9 and 15) and regions having a thickness of greater than 8 mm 20SG Docket No.: 14990-701.600(regions 4, 5, 10 and 11) are shown in a third color marking.

[0068] A bullseye map / image may be included as well as any of the other imaging user interfaces described herein.

[0069] In general, these methods and apparatuses may provide improved techniques and apparatuses (e.g., systems) for fusing 2D fluoroscopic images with 3D MRI or CT images. These methods and apparatuses provide innovative techniques for performing the fusion that may be done quickly and highly accurately and may maintain alignment during real procedures.

[0070] In particular, these methods and apparatuses may use blood pool volumes as a primary registration feature between the 2D fluoroscopic images and the 3D MRI or CT model. These methods and apparatuses may align the 2D and 3D imaging modalities by matching the shapes and boundaries of blood pool volumes, particularly at end-diastole, rather than relying on bones, device shapes, or manually selected anatomical landmarks. The 2D fluoroscopic blood pool and 3D blood pool volumes may be registered to one another to achieve highly accurate spatial alignment, and that diastolic blood pool geometry improves resolution and consistency of the fusion image.Example

[0071] As mentioned above, a method may include receiving (in an image processing apparatus or module as described herein) a 3D image or set of images (e.g., a 3D model) of the heart, taken by MRI or CT. and receiving fluoroscopy images such as two (or in some cases more) views, typically two orthogonal views, such as LAO and RAO views. As described above, these 2D views may be integrated with the 3D images when the image are chosen during systole or, preferably at diastole (e.g., at maximum volume, such as End-Diastolic volume, EDV). The 2D image may be fused after aligning with the 3D image, as described above. During the procedure the resulting images may be updated as the medical device (e.g., catheter(s)) are navigated through the heart. In some cases the bullseye view may be generated and displayed concurrently.

[0072] For example, during a pacing procedure, when the electrophysiological properties of the heart are mapped, one or more mapping electrodes may be probed into the heart and recordings made and annotated onto the 2D / 3D images as described above. For example, the user may automatically, manually or semi -automatically confirm or identify the tip of the device (catheter, mapping electrode, etc.) in both the LAO and ROA views and therefore uniquely identify the location of the device in the 2D / 3D (fusion image) or 3D image / model, and / or bullseye images. The user may mark the image(s) when contacting the tissue, e.g., when taking an electrophysiological reading using one or more mapping electrodes, such as 21SG Docket No.: 14990-701.600with an alphanumeric, color, and / or icon. The user may compare the marking(s) with a predicted mapping of other electrophysiological and / or anatomical landmarks or markings in any of these images.

[0073] In any of these methods, including any conduction system pacing method and / or transendocardial delivery method, a user (e.g., physician) may place a catheter at a point in the heart, marking it on one 2D view and then the other, and, based on the appearance in the images and the bullseye image, may decide to assess pacing thresholds, or perform a transendocardial delivery. This may be repeated multiple times; for example a transendocardial delivery (injection) may be performed 10 to 15 times or more.

[0074] When used for placing one or more electrodes, e.g., for pacing, the user may probe and record, for comparison, multiple regions and mark the image(s) with one or more markers; these images may then be used to allow immediate comparison. The method and apparatus may also record the actual implantation sites for one or more electrodes.Similarely, when used for injecting a material, the injection sites can be recorded and stored.

[0075] During or after a procedure, any of these methods and apparatuses may provide output including outputting one or more of the images (including the fused 2D / 3D images) showing the markings and / or locations of implants and / or injections. For example, any of these methods may include providing a link to a file, and / or may output the file itself, showing the marked-up fused image, 2D image(s), 3D image / model, and / or bullseye image(s). The files and / or links may be secured, including encrypted, and / or may be stripped of any patient-identifying data, to ensure privacy and data security.

[0076] Any of these methods and apparatuses may use external radiopaque markers placed on or near the patient before imaging. These markers may appear both in the pre-procedural 3D images and in the live fluoroscopic views, enabling fast, reliable re-registration if the patient or table moves. This may allow the fluoroscopy system to be repositioned during the procedure without losing registration accuracy. The application emphasizes that one or more radiopaque markers, such as adhesive ECG patches or forceps clipped to the drape, can be used to restore alignment rapidly. This capability is not present in earlier systems that may require the table and C-arm to remain fixed to maintain alignment.

[0077] Any of these methods and apparatuses may use real-time manual annotation that can be performed either in the sterile field or remotely. These annotations can appear simultaneously on the fluoroscopic displays and on the fused 3D-2D images. They can indicate treatment targets, zones to avoid, delivered injection sites, biopsy locations, pacing lead attempts, or other relevant information. The annotations may also be used to drive re-registration, guide catheter navigation, or document procedure history. Prior systems 22SG Docket No.: 14990-701.600generally do not support interactive annotations that dynamically update and propagate through a fused dual-view system in real time.

[0078] The fusion process used in the methods and apparatuses described herein may use two or more orthogonal fluoroscopic views (e.g., RAO and LAO) to maintain accurate 3D consistency. By capturing annotations or target locations in both orthogonal planes, the system computes precise 3D coordinates that update both views accordingly. This may allow catheter tip locations, injection points, or pacing lead placement to be represented consistently in three-dimensional space without requiring biplane hardware that must remain stationary. The approach relies on orthogonal projections and consistent iso-centering to preserve registration even when the imaging geometry changes.

[0079] These methods and apparatuses may not require the table or C-arm to remain fixed after initial registration. Because the radiopaque markers can be used to rapidly re-register after movement, the physician may be free to reposition the imaging equipment at any time during the procedure. This flexibility is not present in traditional systems, where movement typically invalidates the registration and necessitates a full recalibration.

[0080] Any of these methods and apparatuses may also incorporate functional myocardial data directly into the fused fluoroscopic projection. This may include infarct location, infarct size, peri-infarct zones, myocardial wall thickness, regions of hypokinesis or akinesis, contraction properties, and other physiology-based information derived from MRI or CT. In some cases, displaying this information directly over the live fluoroscopy may provide actionable guidance for transendocardial injections, biopsies, or pacing, enhancing safety and precision. Earlier methods typically overlay only anatomical contours, not functional or treatment-specific regional data.

[0081] As mentioned, any of these methods and apparatuses may include one or more dynamic bullseye (craniocaudal) map that updates in real time with the catheter’s position and displays regional functional data, target zones, and / or treatment histories. Traditionally, bullseye maps are static views generated offline from imaging studies and are not integrated with live catheter guidance. Here, the bullseye map becomes an interactive tool that reflects both anatomy and real-time procedural activity.

[0082] Finally, any of these methods and apparatuses may include algorithm-driven selection of target sites for injections, biopsies, or pacing. These algorithms can distribute target locations according to user-defined rules, such as proximity to infarct zones, required wall thickness, spacing between injection sites, and exclusion of previously treated or unsafe areas. After each treatment, the system can automatically recalculate and adjust the remaining target sites. This dynamic, procedure-responsive planning may provide advantages not 23SG Docket No.: 14990-701.600previously possible in conventional imaging systems.

[0083] The methods and apparatuses for fusion imaging described herein may provide continuous, re-registrable, functionally informed, annotation-driven procedural guidance. The approach integrates pre-procedural 3D imaging with intraoperative 2D fluoroscopy in a way that supports precise navigation, dynamic targeting, ongoing documentation, and enhanced safety for procedures such as transendocardial injections, biopsies, and / or conduction-system pacing.Numbered Embodiments.

[0084] Embodiment 1. A method for imaging a heart of a subject, said method comprising: combining at least one two-dimensional (2D) image of the heart and a three-dimensional (3D) image of the heart to generate a fusion image, wherein blood pool volumes of the at least one 2D image and the 3D image are registered to one another to align the images in the fusion image.

[0085] Embodiment 2. The method of embodiment 1, wherein combining the at least one 2D image of the heart and the 3D image of the heart comprises overlaying the at least one 2D image of the heart on the 3D image of the heart.

[0086] Embodiment 3. The method of embodiment 1, wherein combining the at least one 2D image of the heart and the 3D image of the heart comprises overlaying the 3D image of the heart on the at least one 2D image of the heart.

[0087] Embodiment 4. The method of any of the preceding embodiments, wherein the at least one 2D image of the heart comprises at least two orthogonal 2D images of the heart.

[0088] Embodiment 5. The method of any of the preceding embodiments, wherein the at least one 2D image of the heart comprise a fluoroscopic image.

[0089] Embodiment 6. The method of embodiment 5, wherein the fluoroscopic image was taken using a contrast agent.

[0090] Embodiment 7. The method of embodiment 6, wherein the contrast agent comprises a radioactive tracer.

[0091] Embodiment 8. The method of any of the preceding embodiments, wherein 3D image of the heart comprises a CT image or an MRI image.

[0092] Embodiment 9. The method of any of the preceding embodiments, wherein the blood pool volumes comprise a first blood pool volume and a second blood pool volume and wherein combining the 3D image with the least one 2D image comprises mapping a first blood pool volume and second blood pool volume to one another.

[0093] Embodiment 10. The method of embodiment 9, wherein the first blood pool volume is taken at a first time point and wherein the second blood pool volume is taken at a 24SG Docket No.: 14990-701.600second time point.

[0094] Embodiment 11. method of any of the preceding embodiments , wherein the blood pool volumes are taken at or adjacent an end of a diastolic phase.

[0095] Embodiment 12. The method of any of the preceding embodiments, wherein the blood pool volumes are taken in time series.

[0096] Embodiment 13. The method of any of the preceding embodiments, wherein the blood pool volumes show a volume at least one of a left ventricle or a right ventricle.

[0097] Embodiment 14. The method of any of the preceding embodiments, wherein the blood pool volumes comprise blood pool volumes taken after the subject has exercised.

[0098] Embodiment 15. The method of any of the preceding embodiments, wherein the blood pool volumes are generated by a first-pass scan.

[0099] Embodiment 16. The method of any of the preceding embodiments, wherein the blood pool volumes are generated by a multi-gated acquisition scan (MUGA) scan.

[0100] Embodiment 17. The method of any of the preceding embodiments, further comprising generating the blood pool volumes while treating the subject.

[0101] Embodiment 18. The method of any of the preceding embodiments, wherein the blood pool volumes comprise at least one blood pool volume is not at maximum diastole.

[0102] Embodiment 19. The method of any of the preceding embodiments, further comprising receiving at least one manual marking or annotation on at least one of the 3D image, the at least one 2D image, or the fusion image.

[0103] Embodiment 20. The method of embodiment 19, wherein the at least one manual marking or annotation is configured to facilitate registration or re-registration of the at least one 2D image to the 3D image.

[0104] Embodiment 21. The method of any one of embodiments 19-20, wherein the at least one manual marking or annotation is received from an operator in a same operating field as the subject.

[0105] Embodiment 22. The method of any one of embodiments 19-21 wherein the at least one manual marking or annotation is received from an operate in a location remote from the subject.

[0106] Embodiment 23. The method of any one of embodiments 19-22, wherein registering the at least one 2D image with the 3D image is based at least in part on the at least one manual marking or annotation.

[0107] Embodiment 24. The method of any one of embodiments 19-23, wherein the at least one manual marking or annotation indicates a prior location of an intervention or biotherapeutic agent delivery.25SG Docket No.: 14990-701.600

[0108] Embodiment 25. The method of any one of embodiments 19-24, wherein the at least one manual marking or annotation indicates a location not suitable to receive an intervention or biotherapeutic agent delivery.

[0109] Embodiment 26. The method of any of the preceding embodiments, wherein registering the at least one 2D image with the 3D image is based at least in part on at least one opaque marker.

[0110] Embodiment 27. The method of embodiment 26, wherein the at least one opaque marker comprises a radiopaque marker or a fluoroscopically opaque marker.[oni] Embodiment 28. The method of any of the preceding embodiments, further comprising performing one or more of a transendocardial biotherapeutic agent delivery procedure, a biopsy procedure, or an HPS conduction system pacing procedure based on the fusion image.

[0112] Embodiment 29. The method of any of the preceding embodiments, wherein the 3D image comprises anatomical or treatment information prior to combining the at least one 2D image of the heart and the 3D image of the heart.

[0113] Embodiment 30. The method of embodiment 29, wherein the anatomical information comprises one or more of location information on regions of myocardial infarction, wall thickness, and contraction properties of the heart.

[0114] Embodiment 31. A method for imaging a heart of a subject, said method comprising: combining at least one two-dimensional (2D) image of the heart and a three-dimensional (3D) image of the heart to generate a fusion image, wherein a same at least one opaque marker in the at least one 2D image and also in the 3D image are registered to one another to align the images in the fusion image, wherein the at least one marker is placed on or near the subject prior to the at least one 2D image and the 3D image being generated.

[0115] Embodiment 32. The method of embodiment 31, wherein combining the at least one 2D image of the heart and the 3D image of the heart comprises overlaying the at least one 2D image of the heart on the 3D image of the heart.

[0116] Embodiment 33. The method of embodiment 31, wherein combining the at least one 2D image of the heart and the 3D image of the heart comprises overlaying the 3D image of the heart on the at least one 2D image of the heart.

[0117] Embodiment 34. The method of any one of embodiments 31-33, wherein the at least one 2D image of the heart comprises 2 orthogonal 2D images of the heart.

[0118] Embodiment 35. The method of any one of embodiments 31-34, wherein the at least one 2D image of the heart comprises a fluoroscopic image.

[0119] Embodiment 36. The method of any one of embodiments 31-35, wherein the 3D 26SG Docket No.: 14990-701.600image of the heart comprises a CT image or an MRI image.

[0120] Embodiment 37. The method of any one of embodiments 31-36, wherein the at least one opaque marker comprises one or more radio-opaque markers.

[0121] Embodiment 38. The method of embodiment 37, wherein the one or more radio opaque markers are positioned in an X-Ray image field can be on or near the subject's chest or back.

[0122] Embodiment 39. The method of any one of embodiments 31-38, wherein the at least one opaque marker is configured to appear on a live fluoroscopy image.

[0123] Embodiment 40. The method of embodiment 39, wherein the at least one opaque marker is marked on at least one of the at least one 2D image, the 3D image, or the fusion image before or after generating the fusion image.

[0124] Embodiment 41. The method of any one of embodiments 31-40, wherein the at least one opaque marker comprises at least two orthogonal markers.

[0125] Embodiment 42. The method of any one of embodiments 31-41, wherein the at least one opaque marker comprises an adhesive electrocardiogram electrode patch or a forceps clip.

[0126] Embodiment 43. The method of any one of embodiments 31-42, wherein the at least one opaque marker is configured to facilitate registration or re-registration of the 2D image to 3D image.

[0127] Embodiment 44. The method of any one of embodiments 31-43, wherein the same at least one opaque marker are registered to one another, after a physician is in position to perform a procedure and prior to the start of the procedure.

[0128] Embodiment 45. A method for imaging a heart of a subject, said method comprising: combining at least one two-dimensional (2D) image of the heart and a three-dimensional (3D) image of the heart to generate a fusion image, wherein one or more manual markers or annotations generated by a user on at least the 3D image configured to identify a region of interest in the heart or align the least one two-dimensional (2D) image and the 3D image.

[0129] Embodiment 46. The method of embodiment 45, wherein combining the at least one 2D image of the heart and the 3D image of the heart comprises overlaying the at least one 2D image of the heart on the 3D image of the heart.

[0130] Embodiment 47. The method of any one of embodiments 45, wherein combining the at least one 2D image of the heart and the 3D image of the heart comprises overlaying the 3D image of the heart on the at least one 2D image of the heart.

[0131] Embodiment 48. The method of any one of embodiments 45-47, wherein the at 27SG Docket No.: 14990-701.600least one 2D image of the heart comprises at least two orthogonal 2D images of the heart.

[0132] Embodiment 49. The method of any one of embodiments 45-48, wherein the at least one 2D image of the heart comprises a fluoroscopic image of the heart.

[0133] Embodiment 50. The method of any one of embodiments 45-49, wherein the 3D image of the heart comprises a CT image or an MRI image.

[0134] Embodiment 51. The method of any one of embodiments 45-50, wherein the wherein one or more manual markers or annotations generated by a user are configured to facilitate registration or re-registration of the at least one 2D image to the 3D image.

[0135] Embodiment 52. The method of any one of embodiments 45-51, wherein the wherein one or more manual markers or annotations generated by a user, is received from an operator in a same operating field as the subject.

[0136] Embodiment 53. The method of any one of embodiments 45-52, wherein the wherein one or more manual markers or annotations generated by a user is received from an operator in a location remote from the subject.

[0137] Embodiment 54. The method of any one of the preceding claims, further comprising treating one or more conditions of the heart.

[0138] Embodiment 55. The method of embodiment 54, wherein treating one or more conditions of the heart comprise performing one or more of a transendocardial biotherapeutic agent delivery procedure, a biopsy procedure, or an HPS conduction system pacing procedure based on the fusion image.

[0139] Embodiment 56. The method of embodiment 55, wherein at least one of the one or more manual markers or annotations mark are generated after performing one or more of the transendocardial therapeutic agent delivery procedure, the biopsy procedure, or the HPS conduction system pacing procedure.

[0140] Embodiment 57. The method of embodiment 56, wherein the at least one of the one or more manual markers or annotations mark are configured to identify at least a location of the heart that has been treated or was identified as a location not suitable to receive treatment.

[0141] Embodiment 58. The method of embodiment 57, wherein the at least one of the one or more manual markers or annotations mark comprise a first set of markers configured to identify at least a location of the heart that has been treated and a second set of markers configured to identify locations not suitable to receive treatment.

[0142] Embodiment 59. A method for an image guided cardiac procedure, the method comprising: generating a fusion image as described in any of the preceding claims; further simulating an anatomy of the heart of the subject using the fused image; and displaying the 28SG Docket No.: 14990-701.600simulated anatomy of the heart on a display to help guide a positioning, placement, or both of a device for treatment, diagnosis, or both of a cardiac condition of the subject.

[0143] Embodiment 60. The method of embodiment 59, wherein the device comprises a helical tip configured to pierce the cardiac tissue of the subject.

[0144] Embodiment 61. The method of any one of embodiments 59-60, wherein the device comprises a cardiac electrode configured for HPS pacing.

[0145] Embodiment 62. The method of any one of embodiments 59-61, further comprising generating one or more manual annotations or marks on least one of the 3D image, the at least one 2D image, or the fusion image during positioning or placement of the device.

[0146] Embodiment 63. The method of embodiment 62, wherein the one or more manual markings or annotations show an angle of insertion or positioning of the device.

[0147] Embodiment 64. The method of embodiment 62, wherein the one or more manual markings or annotations show an optimal placement zone at or near a target for pacing.

[0148] Embodiment 65. The method of any one of embodiments 59-64, further comprising measuring a current at a location of the device.

[0149] Embodiment 66. The method of embodiment 65, wherein the measured current is used to confirm a placement of the device.

[0150] Embodiment 67. The method of embodiment 66, wherein confirming the placement of the device comprises assessing pacing capture or assessing the lowest voltage of successfully capture.

[0151] Embodiment 68. The method of embodiment 67, wherein assessing pacing capture is based at least in part on an analysis of at least one of a paced QRS morphology, a peak left ventricular activation time, or other metrics.

[0152] Embodiment 69. The method of any of the proceeding claims, further comprising visually enhancing one or more structures of interest in the fusion image.

[0153] Embodiment 70. The method of embodiment 69, wherein visually enhancing the one or more structures of interest in the fused image comprises annotating the 3D image.

[0154] Embodiment 71. The method of embodiment 62, further comprising wherein the one or more manual markings or annotations comprise one or more of a previous position of the device or a vector of the device during placement.

[0155] Embodiment 72. The method of embodiment 71, further comprising annotating or marking a final position and vector of the device after placement.29SG Docket No.: 14990-701.600

[0156] Embodiment 73. The method of any one of embodiments 59-62, wherein at least a part of the device comprises a radiopaque material.

[0157] Embodiment 74. A method for imaging a heart of a subject, said method comprising: receiving a three-dimensional (3D) image of the heart, the 3D image comprising a first blood pool volume; imaging the heart using an x-ray fluoroscopy system and a contrast agent to produce at least one two-dimensional (2D) image of the heart, wherein the at least one 2D image of the heart comprises a second blood pool volume; and registering the least one 2D image with the 3D image based at least in part on the first and second blood pool volumes, thereby generating a fusion image of the heart.

[0158] Embodiment 75. A method for imaging of a heart of a subject, said method comprising: receiving a three-dimensional (3D) image of the heart, wherein the 3D image shows a first location of at least one opaque marker placed on the subject; imaging the heart using an X-ray fluoroscopy system to produce at least one two-dimensional (2D) image of the heart, wherein the at least one 2D image of the heart shows a second location of the at least one opaque marker placed on the subject; and registering the least one 2D image with the 3D image based at least in part on the first and second locations of the at least one opaque marker, thereby generating a fusion image of the heart.

[0159] Embodiment 76. A method for imaging of a heart of a subject, said method comprising: receiving a three-dimensional (3D) image of the heart; imaging the heart using an x-ray fluoroscopy system to produce at least one two-dimensional (2D) image of the heart; registering the least one 2D image with the 3D image, thereby generating a fusion image of the heart; and receiving at least one manual marking or annotation to the 2D image, wherein (i) the at least one manual marking or annotation indicates a prior location of an intervention or biotherapeutic agent delivery, (ii) wherein the at least one manual marking or annotation indicates location not suitable for an intervention or biotherapeutic agent delivery, or both (i) and (ii).

[0160] Embodiment 77. A method for an image guided cardiac procedure, the method comprising: performing pre-procedural three-dimensional (3D) imaging of the heart to generate at least one pre-procedural 3D image of the heart of subject; identifying one or more regions of interest on the at least one 3D image of the heart; performing blood pool imaging of the heart and receiving at least one blood pool volume image; performing fluoroscopic x-ray imaging of the heart to generate at least one fluoroscopic image of the heart; generating a fused fluoroscopy image by aligning the at least one blood pool volume image with the one or more regions of interest of the at least one pre-procedural 3D image; simulating the anatomy of the heart using the fused fluoroscopy image; and 30SG Docket No.: 14990-701.600displaying the simulated anatomy of the heart on a display to help guide a positioning, placement, or both of a device for treatment, diagnosis, or both of a cardiac condition of the subject.

[0161] Also described herein are fusion imaging apparatuses (e.g., systems) that may use blood pool registration.

[0162] Embodiment 78. An image fusion system for cardiac procedures, comprising: a fluoroscopy subsystem configured to acquire (e.g., receive and / or take) at least one two dimensional fluoroscopic image of a subject’s heart; a three dimensional imaging subsystem configured to receive and / or provide a three dimensional cardiac image of the subject obtained by magnetic resonance imaging or computed tomography; and one or more processors coupled to a non-transitory memory storing instructions that, when executed, cause the processors to: identify, in the at least one fluoroscopic image, a first blood pool volume of at least one cardiac chamber; identify, in the three dimensional cardiac image, a second blood pool volume corresponding to the at least one cardiac chamber; compute a spatial transform that registers the at least one fluoroscopic image to the three dimensional cardiac image based at least in part on alignment of the first and second blood pool volumes; and render, on a display, a fusion image comprising an overlay of the three dimensional cardiac image and the at least one fluoroscopic image in the registered geometry. Any of these apparatuses may include a display.

[0163] Embodiment 79. The system of embodiment 78, wherein the processors are further configured to select the second blood pool volume at or near end diastole.

[0164] Embodiment 80. The system of embodiment 78, wherein the fluoroscopy subsystem acquires two orthogonal, iso centered projections and the processors register both projections to the three dimensional cardiac image concurrently.

[0165] Embodiment 81. The system of embodiment 78, wherein the processors are configured to overlay functional myocardial information from the three dimensional cardiac image including one or more of infarct location, wall thickness, or regional contractility.

[0166] Embodiment 82. The system of embodiment 78, wherein the fluoroscopy subsystem injects contrast and the processors segment the first blood pool volume from a high contrast ventriculogram.

[0167] Embodiment 83. The system of embodiment 78, wherein the processors maintain registration while permitting C arm rotation without changing table position or magnification, and prompt re registration when imaging geometry changes beyond a threshold.31SG Docket No.: 14990-701.600

[0168] Embodiment 84. The system of embodiment 78, wherein the fusion image concurrently displays right anterior oblique and left anterior oblique views that share a common three dimensional coordinate frame.

[0169] Embodiment 85. The system of embodiment 78, further comprising a catheter tracking module configured to compute a three dimensional catheter tip position from two orthogonal annotations and to project the three dimensional position into the fusion image.

[0170] Embodiment 86. The system of embodiment 78, wherein the processors are configured to log procedural events, including injection sites, biopsy sites, or pacing lead attempts, with timestamps and segment identifiers.

[0171] Embodiment 87. The system of embodiment 78, wherein the three dimensional imaging subsystem comprises cardiac images preprocessed to reconstruct endocardial and epicardial surfaces and infarct zones prior to fusion.

[0172] Also described herein are apparatuses for marker assisted re registration and motion management.

[0173] Embodiment 88. A fluoroscopy-three dimensional cardiac fusion apparatus, comprising: a fluoroscopy subsystem; a three dimensional imaging data source comprising a cardiac volume; a set of patient mounted radiopaque markers configured to be visible in both the fluoroscopy subsystem and the three dimensional imaging data source; a display; and one or more processors configured to: determine first locations of the radiopaque markers in the three dimensional imaging data source and second locations of the radiopaque markers in at least one fluoroscopic frame; compute a registration transform between the at least one fluoroscopic frame and the three dimensional imaging data source based at least in part on correspondence of the first and second locations; and upon detecting patient or table motion, reestablish the registration transform using updated second locations of the radiopaque markers without reacquiring the three dimensional imaging data source.

[0174] Embodiment 89. The apparatus of embodiment 88, wherein the radiopaque markers comprise adhesive electrode patches or sterile clips placed on or near the chest or back of the subject.

[0175] Embodiment 90. The apparatus of embodiment 88, wherein the processors detect motion by monitoring geometric consistency of the radiopaque markers across sequential fluoroscopic frames.

[0176] Embodiment 91. The apparatus of embodiment 88, wherein the apparatus is configured to maintain registration across right anterior oblique and left anterior oblique 32SG Docket No.: 14990-701.600projections acquired on a single plane C arm by re registration to the radiopaque markers after C arm rotation.

[0177] Embodiment 92. The apparatus of embodiment 88, wherein the processors combine marker based re registration with blood pool based registration to refine alignment.

[0178] Embodiment 93. The apparatus of embodiment 88, wherein the apparatus issues a visual prompt on the display to confirm re registration when an imaging geometry change exceeds a preset limit.

[0179] Embodiment 94. The apparatus of embodiment 88, wherein the apparatus maintains an audit record of registration and re registration events with timestamps and error metrics.

[0180] Also described herein are apparatuses configured for interactive annotation and dual view three dimensional consistency.

[0181] Embodiment 95. An image guided cardiac intervention system, comprising: one or more processors configured to: register fluoroscopic images to a three dimensional cardiac image; receive, from either a sterile field display or a remote workstation, user generated annotations identifying one or more of target treatment zones, avoidance zones, or procedural events; compute three dimensional coordinates of an annotation from corresponding annotations in two orthogonal fluoroscopic views; and project the three dimensional coordinates back into both orthogonal views and into a three dimensional overlay in real time. Any of these apparatuses may optionally include a fluoroscopy imaging device and / or a three dimensional cardiac image source, and / or a first display configured to be positioned in a sterile field and / or a second display configured to be at a remote workstation.

[0182] Embodiment 96. The system of embodiment 95, wherein annotations comprise alphanumeric labels, color coding, or pattern coding that distinguish delivered sites from planned sites.

[0183] Embodiment 97. The system of embodiment 95, wherein the processors toggle visibility and transparency of annotations independently for each view.

[0184] Embodiment 98. The system of embodiment 95, wherein the processors store, for each annotated site, at least one of a wall thickness value, a distance to an infarct boundary, an electrophysiologic metric, or a segment identifier.

[0185] Embodiment 99. The system of embodiment 95, further comprising a catheter tip localization module that constrains a target cursor to an endocardial surface in a shared three dimensional coordinate frame while the user selects treatment points.33SG Docket No.: 14990-701.600

[0186] Embodiment 100. The system of embodiment 95, wherein the remote workstation communicates bidirectionally with the sterile field display to synchronize annotations and overlays over a network link.

[0187] Also described herein are apparatuses for dynamic bullseye rendering and algorithmic targeting.

[0188] Embodiment 101. A cardiac visualization apparatus, comprising: a fusion engine configured to register at least one two dimensional fluoroscopic view to a three dimensional cardiac image; a rendering engine configured to generate, from the three dimensional cardiac image, a polar bullseye map of myocardial segments in a craniocaudal projection; a targeting engine configured to compute a set of candidate treatment sites according to user defined constraints; and an output (e.g., display) configured to present the bullseye map concurrently with the registered fluoroscopic view, wherein catheter position is indicated on both displays in real time.

[0189] Embodiment 102. The apparatus of embodiment 101, wherein the rendering engine encodes regional wall motion and / or wall thickness for the myocardial segments.

[0190] Embodiment 103. The apparatus of embodiment 101, wherein the targeting engine enforces constraints including minimum wall thickness, distance from an infarct boundary, spacing between treatment sites, exclusion of previously treated sites, or combinations thereof.

[0191] Embodiment 104. The apparatus of embodiment 101, wherein the targeting engine automatically recalculates remaining candidate sites after each completed treatment and updates both the bullseye map and the registered fluoroscopic overlay.

[0192] Embodiment 105. The apparatus of embodiment 101, wherein the apparatus assigns each treated site to a left ventricular segment identifier and logs the assignment with a timestamp and dosage or sampling metadata.

[0193] Embodiment 106. The apparatus of embodiment 101, wherein the rendering engine is configured to display target regions, delivered sites, and avoidance zones using distinct visual encodings.

[0194] Also described herein are apparatuses for generating conduction system pacing guidance overlay

[0195] Embodiment 107. A conduction system pacing guidance system, comprising: a fusion overlay engine configured to register a three dimensional cardiac image to at least one two dimensional fluoroscopic view; a conduction system model including estimated locations of at least one of the His bundle, left bundle branch, or left bundle branch area derived from the three dimensional cardiac image; a pacing lead visualization 34SG Docket No.: 14990-701.600module configured to display, in the fusion overlay, a position and insertion vector of a pacing electrode; and one or more processors configured to annotate, store, and display pacing capture metrics for attempted lead positions.

[0196] Embodiment 108. The system of embodiment 107, wherein the fusion overlay highlights valvular annuli and adjacent structures with distinct encodings to guide lead implantation while avoiding valve injury.

[0197] Embodiment 109. The system of embodiment 107, wherein the processors record, for each attempted lead position, a pacing threshold, a peak left ventricular activation time, and a paced QRS morphology identifier.

[0198] Embodiment 110. The system of embodiment 107, wherein the pacing lead visualization module records the insertion vector at non final attempts and the final lead vector upon implantation.

[0199] Embodiment 111. The system of embodiment 107, wherein the system supports re registration during the procedure by using patient mounted radiopaque markers visible in both the three dimensional cardiac image and fluoroscopy.

[0200] Also described herein are apparatuses for two dimensional model fitting alternative

[0201] Embodiment 112. An apparatus for fluoroscopic guidance using a two dimensional cardiac model, comprising: a fluoroscopy subsystem configured to acquire (e.g., receive or take) right anterior oblique and left anterior oblique projections of a ventricle; a two dimensional model generator configured to reconstruct, from pre procedural imaging, a two dimensional model of the ventricle in planes corresponding to the right anterior oblique and left anterior oblique projections; a registration engine configured to fit the two dimensional model to the right anterior oblique and left anterior oblique projections; and a display configured to present the fitted two dimensional model as an overlay with treatment zones and avoidance zones pre encoded thereon.

[0202] Embodiment 113. The apparatus of embodiment 112, wherein the apparatus accepts user defined annotations on the fitted two dimensional model and propagates corresponding three dimensional coordinates into a shared coordinate frame with the right anterior oblique and left anterior oblique projections.

[0203] Embodiment 114. The apparatus of embodiment 112, wherein the apparatus logs delivered treatment locations and volumes with time and view coordinates for subsequent review.

[0204] While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are 35SG Docket No.: 14990-701.600provided by way of example only. It is not intended that the present disclosure be limited by the specific examples provided within the specification. While the present disclosure has been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the present disclosure. Furthermore, it shall be understood that all aspects of the present disclosure are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It can be understood that various alternatives to the embodiments of the present disclosure described herein may be employed in practicing the present disclosure. It is therefore contemplated that the present disclosure shall also cover any such alternatives, modifications, variations or equivalents. It is intended that the following claims define the scope of the present disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.36SG Docket No.: 14990-701.600

Claims

CLAIMSWhat is claimed is:

1. A method for imaging a heart of a subject, said method comprising:combining at least one two-dimensional (2D) image of the heart and a three- dimensional (3D) image of the heart to generate a fusion image, wherein blood pool volumes of the at least one 2D image and the 3D image are registered to one another to align the images in the fusion image.

2. The method of claim 1, wherein combining the at least one 2D image of the heart and the 3D image of the heart comprises overlaying the at least one 2D image of the heart on the 3D image of the heart.

3. The method of claim 1, wherein combining the at least one 2D image of the heart and the 3D image of the heart comprises overlaying the 3D image of the heart on the at least one 2D image of the heart.

4. The method of any of the preceding claims, wherein the at least one 2D image of the heart comprises at least two orthogonal 2D images of the heart.

5. The method of any of the preceding claims, wherein the at least one 2D image of the heart comprise a fluoroscopic image.

6. The method of claim 5, wherein the fluoroscopic image was taken using a contrast agent.

7. The method of claim 6, wherein the contrast agent comprises a radioactive tracer.

8. The method of any of the preceding claims, wherein the 3D image of the heart comprises a CT image or an MRI image.

9. The method of any of the preceding claims, wherein the blood pool volumes comprise a first blood pool volume and a second blood pool volume and wherein combining the 3D image with the least one 2D image comprises mapping a first blood pool volume and second blood pool volume to one another.

10. The method of claim 9, wherein the first blood pool volume is taken at a first time point and wherein the second blood pool volume is taken at a second time point.37SG Docket No.: 14990-701.60011. The method of any of the preceding claims, wherein the blood pool volumes are taken at or adjacent an end of a diastolic phase.

12. The method of any of the preceding claims, wherein the blood pool volumes are taken in time series.

13. The method of any of the preceding claims, wherein the blood pool volumes show a volume at least one of a left ventricle or a right ventricle.

14. The method of any of the preceding claims, wherein the blood pool volumes comprise blood pool volumes taken after the subject has exercised.

15. The method of any of the preceding claims, wherein the blood pool volumes are generated by a first-pass scan.

16. The method of any of the preceding claims, wherein the blood pool volumes are generated by a multi -gated acquisition scan (MUGA) scan.

17. The method of any of the preceding claims, further comprising treating the subject generating the blood pool volumes while treating the subject.

18. The method of any of the preceding claims, wherein the blood pool volumes comprise at least one blood pool volume is not at maximum diastole.

19. The method of any of the preceding claims, further comprising receiving at least one manual marking or annotation on at least one of the 3D image, the at least one 2D image, or the fusion image.

20. The method of claim 19, wherein the at least one manual marking or annotation is configured to facilitate registration or re-registration of the at least one 2D image to the 3D image.

21. The method of any one of claims 19-20, wherein the at least one manual marking or annotation is received from an operator in a same operating field as the subject.

22. The method of any one of claims 19-20, wherein the at least one manual marking or annotation is received from an operate in a location remote from the subject.

23. The method of any one of claims 19-22, wherein registering the at least one 2D 38SG Docket No.: 14990-701.600image with the 3D image is based at least in part on the at least one manual marking or annotation.

24. The method of any one of claims 19-23, wherein the at least one manual marking or annotation indicates a prior location of an intervention or biotherapeutic agent delivery.

25. The method of any one of claims 19-24, wherein the at least one manual marking or annotation indicates a location not suitable to receive an intervention or biotherapeutic agent delivery.

26. The method of any of the preceding claims, wherein registering the at least one 2D image with the 3D image is based at least in part on at least one opaque marker.

27. The method of claim 26, wherein the at least one opaque marker comprises a radiopaque marker or a fluoroscopically opaque marker.

28. The method of any of the preceding claims, further comprising performing one or more ofatransendocardial biotherapeutic agent delivery procedure, a biopsy procedure, oranHPS conduction system pacing procedure based on the fusion image.

29. The method of any of the preceding claims, wherein the 3D image comprises anatomical or treatment information prior to combining the at least one 2D image of the heart and the 3D image of the heart.

30. The method of claim 29, wherein the anatomical information comprises one or more of location information on regions of myocardial infarction, wall thickness, and contraction properties of the heart.

31. The method of any of the preceding claims, further comprising generating a bullseye image of the heart based on the 3D image.

32. The method of claim 11, further comprising incorporating anatomical information comprising at least one of infarct location, wall thickness, wall motion, conduction-system landmarks, or target treatment regions on the bullseye image.

33. The method of claim 11, further comprising display on the bullseye image one or more markings corresponding to one or more markings from the at least one 2D image.39SG Docket No.: 14990-701.60034. A method for imaging a heart of a subject, said method comprising:combining at least one two-dimensional (2D) image of the heart and athree dimensional (3D) image of the heart to generate a fusion image, wherein a same at least one opaque marker in the at least one 2D image and also in the 3D image are registered to one another to align theimages in the fusion image, wherein the at least one marker is placed on or near the subject prior to the at least one 2D image or the 3Dimage being generated.

35. A method for imaging a heart of a subject, said method comprising:combining at least one two-dimensional (2D) image of the heart and athree-dimensional (3D) image of the heart to generate a fusion image, wherein one or more manual markers or annotations generated by a user on at least the 3D image configured to identify a region of interest in the heart or align the least one two-dimensional (2D) image and the 3D image.

36. A method for an image guided cardiac procedure, the method comprising:generating a fusion image as described in any of the preceding claims; further simulating an anatomy of the heart of the subject using the fused image; and displaying the simulated anatomy of the heart on a display to help guide a positioning, placement, or both of a device for treatment, diagnosis, or both of a cardiac condition of the subject.

37. A method for imaging a heart of a subject, said method comprising:receiving a three-dimensional (3D) image of the heart, the 3D image comprising a first blood pool volume;imaging the heart using an x-ray fluoroscopy system and a contrast agent to produce at least one two-dimensional (2D) image of the heart, wherein the at least one 2D image of the heart comprises a second blood pool volume; and registering the least one 2D image with the 3D image based at least in part on the first and second blood pool volumes, thereby generating a fusion image of the heart.

38. A method for imaging of a heart of a subject, said method comprising:receiving a three-dimensional (3D) image of the heart, wherein the 3D image shows40SG Docket No.: 14990-701.600a first location of at least one opaque marker placed on the subject; imaging the heart using an X-ray fluoroscopy system to produce at least one two- dimensional (2D) image of the heart, wherein the at least one 2D image of the heart shows a second location of the at least one opaque marker placed on the subject; andregistering the least one 2D image with the 3D image based at least in part on the first and second locations of the at least one opaque marker, thereby generating a fusion image of the heart.

39. A method for imaging of a heart of a subject, said method comprising:receiving a three-dimensional (3D) image of the heart;imaging the heart using an x-ray fluoroscopy system to produce at least one two-dimensional (2D) image of the heart;registering the least one 2D image with the 3D image, thereby generating a fusion image of the heart; andreceiving at least one manual marking or annotation to the 2D image, wherein (i) the at least one manual marking or annotation indicates a prior location of an intervention or biotherapeutic agent delivery, (ii) wherein the at least one manual marking or annotation indicates location not suitable for an intervention or biotherapeutic agent delivery, or both (i) and (ii).

40. A method for an image guided cardiac procedure, the method comprising:performing pre-procedural three-dimensional (3D) imaging of the heart to generate at least one pre-procedural 3D image of the heart of subject;identifying one or more regions of interest on the at least one 3D image of the heart; performing blood pool imaging of the heart and receiving at least one blood pool volume image;performing fluoroscopic x-ray imaging of the heart to generate at least one fluoroscopic image of the heart;generating a fused fluoroscopy image by aligning the at least one blood pool volume image with the one or more regions of interest of the at least one pre- procedural 3D image;simulating the anatomy of the heart using the fused fluoroscopy image; and displaying the simulated anatomy of the heart on a display to help guide a positioning, placement, or both of a device for treatment, diagnosis, or both of a 41SG Docket No.: 14990-701.600cardiac condition of the subject.42SG Docket No.: 14990-701.600

Images