Entry and update using target site selection and automated remote image annotation.

Abstract

To provide a target site selection, entry and update with automatic remote image annotation.SOLUTION: Fluoroscopic imaging of a patient's heart is 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 is simultaneously 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 is manually marked or annotated to show anatomical or treatment information which is simultaneously shown on the operative display. Alternatively, a patient's heart is imaged using a catheter to produce a real time image. The image is presented on a screen and sent to an image processor. Treatment parameters are input to the image processor, and the image processor calculates locations of a plurality of target treatment sites which are displayed on the screen.SELECTED DRAWING: None

Description

Technical Field

[0004] ,

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[0001] (Cross - Reference to Related Applications) This application claims priority based on Provisional Application No. 61 / 750,226 (Attorney Docket No. 29181 - 703.101) filed on January 8, 2013; Provisional Application No. 61 / 750,233 (Attorney Docket No. 29181 - 704.101) filed on January 8, 2013; and Provisional Application No. 61 / 750,237 (Attorney Docket No. 29181 - 705.101) filed on January 8, 2013, the entire contents of which are incorporated herein by reference.

[0002] (Background) 1. Field of the Invention The present invention generally relates to imaging modalities (imaging diagnostic methods), and more specifically, to methods and systems for performing fluoroscopy of biological structures, remotely annotating images, and indicating additional images or other information useful during surgery.

Background Art

[0003] Imaging modalities such as MRI, CT, and echocardiography are used in cardiovascular diagnostic applications and, using custom software, are fused with X - ray fluoroscopy to register and overlay cardiac MRI, CT, or echocardiography - derived two - dimensional (2D) and three - dimensional (3D) images, and endocardium, epicardium, infarcts, and other areas of interest and / or data may be displayed on live X - ray fluoroscopy images.

[0004] Cardiovascular disease is a leading cause of death in developed countries and the number one cause of death in the United States. More than 7.9 million American adults suffer from myocardial infarction (MI), with 1.1 million cases of first-time or recurrent MI each year. MI is characterized by limited blood flow, leading to oxygen deprivation and ultimately massive myocardial loss that cannot regenerate spontaneously, ultimately resulting in heart failure. Existing treatments to restore cardiac function after myocardial injury have so far been limited to strict drug regimens and heart transplantation as a last resort. However, demand far exceeds the supply of healthy donor hearts, leaving the cardiovascular industry to explore novel and promising treatment strategies, including regenerative medicine, gene therapy, and cell therapy. Recent clinical trials are testing different types of stem cells, genes, and growth factors using several delivery routes, including intramyocardial injection, intracoronary infusion, intravenous infusion, and retrograde delivery, as well as both epicardial and transendocardial injections. However, intracardiac transendocardial injection, while minimally invasive, has been shown to improve acute stasis compared to other delivery routes. This improved stasis with transendocardial delivery leads to significant therapeutic potential for tissue regeneration and functional recovery, slowing and ultimately restoring adverse remodeling after myocardial infarction. In recent MI patients, the infarct zone can be extremely fragile, and intracardiac injection in the infarct zone or borderline zone can increase the risk of perforation and pericardial effusion, which can lead to cardiac tamponade, a life-threatening event. In these cases, precise site targeting and injection of biological agents are crucial for patient safety.

[0005] In conventional cardiovascular catheterization procedures, fluoroscopy is typically used by interventional cardiologists to assist in guiding catheters, such as balloon catheters, into occluded arteries within the heart during angioplasty, or guiding catheters using small end-grasping devices during cardiac biopsies, or guiding percutaneous injection catheters into the myocardium for transendocardial injection of biological agents such as cells, genes, peptides, and proteins (e.g., growth factors and chemoattractants). As a result, catheters employed in cardiovascular catheterization procedures are designed to be X-ray visible so that they can be clearly observed and tracked during the procedure. However, using fluoroscopy alone for more complex procedures such as transendocardial injections has several disadvantages, which can significantly affect catheter guidance and image interpretation. (1) X-ray imaging is a projection imaging modality, and typically requires two orthogonal views, namely the right anterior oblique (RAO) and the left anterior oblique (LAO), to obtain a precise sense of the location and orientation of the catheter within the heart in three-dimensional (3D) space. (2) Because two views are required, if the catheterization facility is equipped with a single-planar X-ray fluoroscopy system, the X-ray C-arm must be rotated at a constant rate between these two views throughout the procedure to obtain the required projection and thus enable proper guidance of the transendocardial catheter to the selected intramyocardial target injection site. This is naturally easier if the catheterization facility is equipped with a two-directional X-ray fluoroscopy system. (3) While X-ray imaging provides excellent device visualization, it does not offer much insight into cardiac tissue visualization. X-ray fluoroscopy does not distinguish between healthy tissue and infarcted tissue or tissue within the infarct border zone, nor does it provide a 3D anatomical and topographic view of the patient's heart. This could be particularly important for interventional cardiologists who rely on therapeutic options that attempt to precisely target healthy tissue, infarcted tissue, borderline infarcted tissue, or a combination thereof, for intramyocardial injections of biological agents.For these reasons, image fusion systems that combine X-ray fluorescence fluoroscopy with anatomical and functional 3D models constructed from magnetic resonance (MR) or computed tomography (CT) images, thereby providing real-time information and visualization of catheters, are particularly noteworthy for these applications.

[0006] Magnetic resonance imaging (MRI) is the most accurate diagnostic imaging modality, providing a high-quality 3D anatomical and functional roadmap of a patient's heart, and is therefore most commonly used in combination with radiofluoroscopy in these fused imaging systems. Cardiac MRI compartments, from which cardiac images can be reconstructed, are obtained with excellent tissue contrast. These cardiac images allow for accurate and efficient differentiation between healthy tissue, infarcted tissue, and infarct border zone tissue. However, most catheters and other cardiac devices, while safe for use with and visualization with radiofluoroscopy, are not fully compatible with MRI. Most of these devices contain ferromagnetic materials, which can introduce imaging artifacts and pose a safety risk to the patient due to exposure to a strong magnetic field during MRI. Furthermore, even with the most advanced techniques and instruments available, acquiring MRI images can still take 15 to 60 minutes, depending on the type of image to be acquired and the MRI sequence being initiated. Therefore, it is reasonable to perform an MRI scan prior to the interventional procedure. The cardiac images reconstructed from these scanned sections can then be used in parallel with X-ray fluorescence fluoroscopy to accurately and safely guide the intervening cardiologist to target areas of healthy, infarcted, and / or borderline infarcted tissue for either the injection of biological agents or the sampling of cardiac tissue during transendocardial procedures.

[0007] 2. Explanation of background technology A method and system for fusing preoperative images with information from real-time fluoroscopic images is described in U.S. Patent No. 6,466,813, U.S. Patent Publication Nos. 2008 / 0043901, 2011 / 0087088, and 2011 / 0087110, and Tomkowiak et al. (2011) Catheterization and This is described in Cardiovascular Interventions 78:468-478. See also U.S. Patent No. 7,848,553 and U.S. Patent Publication No. 2013 / 0102890. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] U.S. Patent No. 6,466,813 [Patent Document 2] U.S. Patent Application Publication No. 2008 / 0043901 [Patent Document 3] U.S. Patent Application Publication No. 2011 / 0087088 [Patent Document 4] U.S. Patent Application Publication No. 2011 / 0087110 [Patent Document 5] U.S. Patent No. 7,848,553 [Patent Document 6] U.S. Patent Application Publication No. 2013 / 0102890 [Overview of the Initiative] [Means for solving the problem]

[0009] The object of the present invention is to facilitate the selection and targeting of injection sites for intramyocardial biological drug delivery or other injectable agents in patients suffering from cardiovascular diseases, including chronic heart failure, including chronic myocardial ischemia, acute myocardial infarction, ischemic and non-ischemic heart failure, and dilated cardiomyopathy, using a transendocardial injection catheter equipped with a puncture element at the distal end of the catheter. Biological drug delivery includes cell therapy, gene therapy, protein and peptide therapy, and small molecule drugs. Injectable agent delivery includes, but is not limited to, synthetic polymers, natural biopolymers, and fine particles in the range of 15-150 μm. The present invention can also be used for the selection and targeting of sampling sites for cardiac biopsy procedures to test immunorejection in patients undergoing or who have undergone heart transplantation, patients exhibiting symptoms of cardiomyopathy, cardiac amyloidosis, and myocarditis, or patients from whom cardiac cells are collected for other therapeutic or diagnostic purposes.

[0010] Fluoroscopy of the patient's heart is performed by positioning the patient within a sterile field and using an X-ray fluorescence fluoroscopy system within the sterile field to image the heart and generate a two-dimensional image. The two-dimensional image is displayed simultaneously on an operating room display within or adjacent to the sterile field, and on a remote image processor display outside the operating field. The two-dimensional image on the remote display is manually marked or annotated to indicate anatomical or therapeutic information, which is simultaneously displayed on the operating room display.

[0011] The step of manually marking an image may include the step of operating a graphical user interface on a remote image processor, the graphical user interface including a touchscreen, mouse, rollerball, or joystick. The step of manually marking a two-dimensional image may include the step of marking any one or more of the outline of the heart or a part thereof, a target treatment area, an area to be avoided for treatment, and equivalents.

[0012] In a second aspect of the present invention, the patient's heart is imaged using a catheter to generate real-time images. The images are displayed on a screen and transmitted to an image processor. Treatment parameters are input to the image processor, which calculates the locations of multiple target treatment sites, which are displayed on the screen. The catheter is advanced to position the treatment element on the catheter in close proximity to the locations of the target treatment sites, and the actual location of the treatment element may differ from the calculated location. After treatment at the actual treatment site, the image processor calculates the difference between the calculated treatment site and the actual treatment site location. The locations of all remaining target treatments may be recalculated by the image processor.

[0013] The imaging may include the step of producing a two-dimensional image using X-ray fluorescence fluoroscopy or the step of producing two orthogonal two-dimensional images. The imaging may further include the step of superimposing the outline of the heart onto the two-dimensional image, the superposition may include the step of providing a static three-dimensional image of the heart, the image processor registers the three-dimensional image onto the two-dimensional image, calculates the outline, which is projected onto the two-dimensional image. Alternatively, the superposition may include the step of manually drawing the outline, which is projected onto the two-dimensional image. The method of the present invention may further include the step of repeating the advance, determination, treatment, and recalculation steps for a continuous treatment site.

[0014] In a third aspect, the present invention facilitates the selection and targeting of injection sites for intramyocardial biological drug delivery or other injectable agents in patients suffering from cardiovascular diseases, including chronic heart failure, including chronic myocardial ischemia, acute myocardial infarction, ischemic and non-ischemic heart failure, and dilated cardiomyopathy, using a transendocardial injection catheter equipped with a puncture element at the distal end of the catheter. Biological drug delivery includes cell therapy, gene therapy, protein and peptide therapy, and small molecule drugs. Injectable agent delivery includes, but is not limited to, synthetic polymers, natural biopolymers, and microparticles in the range of 15-150 μm. The present invention can also be used for the selection and targeting of sampling sites for cardiac biopsy procedures to test immunorejection in patients undergoing or who have undergone a heart transplant, patients exhibiting symptoms of cardiomyopathy, cardiac amyloidosis, and myocarditis, or patients from whom their cardiac cells are collected for other therapeutic or diagnostic purposes.

[0015] The patient's heart is imaged using a catheter to generate real-time images, which are displayed on a screen. The images are also sent to an image processor, where treatment parameters are input. The image processor then calculates safe and / or unsafe areas within the heart for treatment or diagnosis based on the input treatment conditions. The image processor overlays information onto the image on the screen to identify safe and / or unsafe areas. The overlaid information may include at least one of the following: color coding, boundary creation, insertion of written information, and insertion of icons.

[0016] The present invention has other advantages and features that will become more readily apparent from the embodiments for carrying out the invention and from the appended claims, upon consideration in conjunction with the accompanying drawings. The present invention provides, for example, the following: (Item 1) A method for fluoroscopy of a patient's heart, The steps include positioning the patient within a sterile field equipped with an X-ray fluorescence fluoroscopy system, Imaging the heart using the fluoroscopy system to generate a two-dimensional image; Simultaneously displaying the two-dimensional image on an in-sterilization-field or adjacent operating room display and on a display of a remote image processor outside the operating room; Manually marking the two-dimensional image on the remote display to indicate anatomical or treatment information simultaneously shown on the operating room display; A method comprising the above steps. (Item 2) The method according to item 1, wherein the step of manually marking the image includes operating a graphical user interface on the remote image processor. (Item 3) The method according to item 2, wherein the graphical user interface includes a touch screen, a mouse, a roller ball, or a joystick. (Item 4) The method according to item 1, wherein the step of manually marking the two-dimensional image includes marking any one or more of an outline of the heart or a part thereof, a target treatment area, and an area to be avoided during treatment. (Item 5) The method according to item 4, wherein the area includes an infarct location, a hypokinetic region, an akinetic region, a papillary muscle, a mitral valve, an apical region of the heart, a His bundle, or a thin region of the heart. (Item 6) A method for treating a patient's heart using a catheter, comprising: Imaging the heart to generate real-time images; Displaying the images on a screen; Transmitting the images to an image processor; Inputting treatment parameters into the image processor, wherein the image processor calculates locations of a plurality of target treatment sites displayed on the screen; A step of advancing the catheter to position a treatment element on the catheter in close proximity to the location of the target treatment site, wherein the actual position of the treatment element may differ from the calculated location of the target treatment site. The steps include treating the tissue using the treatment element at the actual treatment site, The steps include: determining the difference between the actual location of the treatment site and the calculated location of the target treatment site using the image processor; A method comprising the step of using the image processor to recalculate the locations of all remaining target treatment sites that have not yet been treated. (Item 7) The method described in item 6, which includes imaging, by generating a two-dimensional image using X-ray fluorescence fluoroscopy. (Item 8) The method described in item 7, which includes imaging, generating two orthogonal two-dimensional images. (Item 9) The method according to item 6, further comprising imaging the outline of the heart superimposed on the two-dimensional image. (Item 10) The method according to item 9, wherein superimposing includes providing a static three-dimensional image of the heart, the image processor registers the three-dimensional image onto the two-dimensional image, and calculates the outline projected onto the two-dimensional image. (Item 11) The method according to item 10, wherein the static three-dimensional image of the heart includes an image derived from an MRI, CT, or echocardiogram of the heart. (Item 12) The method of item 6, wherein superimposing includes manually drawing the outline projected onto the two-dimensional image. (Item 13) The method according to item 6, further comprising repeating the advance, determination, treatment, and recalculation steps for a continuous treatment site. (Item 14) A procedure method for imaging a patient's heart using a catheter, The steps include imaging the heart in order to produce and generate real-time images, The steps include: displaying the aforementioned image on the screen, The steps include sending the aforementioned image to an image processor, A method comprising the steps of inputting treatment parameters to the image processor, wherein the image processor calculates safe and / or unsafe areas based on the input treatment conditions in order to perform a treatment or diagnosis within the heart, and the image processor superimposes the information onto the image on the screen to identify the safe and / or unsafe areas. (Item 15) The superimposed information is provided in the manner described in item 14, which includes at least one of the following: color coding, creating borders, inserting written information, or inserting icons. [Brief explanation of the drawing]

[0017] [Figure 1] Figure 1-5 illustrates a specific embodiment described below. [Figure 2-1] Figure 1-5 illustrates a specific embodiment described below. [Figure 2-2] Figure 1-5 illustrates a specific embodiment described below. [Figure 2-3] Figure 1-5 illustrates a specific embodiment described below. [Figure 2-4] Figure 1-5 illustrates a specific embodiment described below. [Figure 3] Figure 1-5 illustrates a specific embodiment described below. [Figure 4] Figure 1-5 illustrates a specific embodiment described below. [Figure 5] Figure 1-5 illustrates a specific embodiment described below. [Modes for carrying out the invention]

[0018] (Detailed explanation) In this invention, we combine a 3D model reconstruction of the heart derived from magnetic resonance imaging performed prior to the intervention procedure with live X-ray fluoroscopy during the catheter placement procedure to facilitate catheter guidance within the myocardium and thus improve the safety and accuracy of transcatheter injection of biological and chemotherapy drugs within the affected heart. Cardiac MRI slices detailing the endocardial and epicardial surfaces of the heart, as well as the infarcted area within the heart, are acquired during the MRI scan. Segment (Medviso), The Visualization Toolkit (Kitware, Inc.), QMass(R) MR Ent Commercial platform-independent contouring packages such as erprise Solution (Medis medical imaging system, Inc.) or other freeware are used to define the endocardial and epicardial walls as well as infarcts slice by slice, and thus generate a 3D model of the patient's heart prior to the interventional procedure. It should be noted that any other imaging modality (e.g., CT, echocardiography) that can define the anatomical and functional details of the heart and from which the 3D model can be reconstructed can also be used as an alternative to MRI. The only criterion is the output format from the contouring package, which must conform to the fluoroscopy system. Prior to the procedure, a 3D space within the field of view of the fluoroscopy system is effectively created within the fused imaging system. During the interventional procedure, ventricular contrast images are acquired from the patient's left ventricle in two orthogonal views. The 3D model created from the MRI scan is then effectively placed in the 3D space and registered to conform to the ventricular contrast image of the fluoroscopy system. The 3D model is then transported onto a live X-ray fluoroscopy screen, either in 2D or 3D. The software of the fusion imaging system can then be used to define and display essential parameters and limits central to patient safety treatment, according to the study protocol. For example, in the case of transendocardial intramyocardial injection of a biological agent into the patient's heart, important information such as the location and size of the myocardial infarction, if there are more than one, the distinction between infarct zones, left ventricular wall thickness, areas of motion impairment and akineticity, the targeted injection zone and the "non-injection" zone (including, but not limited to, the papillary muscle, mitral valve, apex, area adjacent to the basal septum where the bundle of His is located, and thin areas of the myocardial wall) are necessary data points for patient safety treatment. These data points can be obtained from an MRI section or CT slice using a software interface and, therefore, prior to the intervention, can be converted into a 2D or 3D model of the heart to create an anatomical and functional roadmap of the heart.Based on the selection and exclusion criteria for intramyocardial injection in each study, specific areas will be traced and bordered using different colors and / or patterns, thus clearly indicating the selected target areas and “non-injection” zones to the intervening cardiologist.

[0019] Here, we disclose specific embodiments for a fusion imaging system with X-ray fluorescence fluoroscopy, cardiac catheterization, and transendocardial injection catheterization, and methods of use for registering and transposing multimodality images and guiding intramyocardial targeted procedures such as transendocardial delivery and cardiac biopsy.

[0020] (Recording of left ventricular contour and target area on screen - 2D)

[0021] (Example 1)

[0022] As mentioned above, one of the main disadvantages of using radiofluoroscopy alone in cardiac interventional procedures is that radiofluoroscopy is a projection imaging modality, which typically requires projections in two orthogonal views, namely the RAO view and LAO view, to determine the location and orientation of a percutaneous catheter in the left ventricle. During a typical transendocardial injection procedure in a catheterization facility equipped with a single-planar radiofluoroscopy system, the two fluoroscopic images are overlaid and fixed on a single monitor of the radiofluoroscopy system. At the start of the procedure, ventricular contrast is performed, during which contrast agent is injected into the left ventricle and the left ventricle is mapped. During mapping, the left ventricular contour of the heart in diastole and systole is traced onto one fluoroscopic image in one orthogonal view. The fluoroscopic image is then flipped out, the C-arm of the fluoroscopy system rotates, and the contour of the heart in diastole and systole is traced onto the second fluoroscopic image within that view. Transendocardial injection is then performed, and each time an injection is administered, the injection site is also marked within both orthogonal views on the two fluoroscopic images. This requires constant switching between orthogonal views and between fluoroscopic images. Depending on the number of injections, this back-and-forth switching of the fluoroscopic images and the C-arm of the fluoroscopy system within each view may be performed multiple times during a single procedure, which can be cumbersome and prolong the procedure. Furthermore, the person changing the overlay should stand near the sterile zone and take care not to accidentally disrupt sterility. The person is also typically standing near the C-arm of the X-ray fluorescence fluoroscopy system and therefore could be unintentionally exposed to a significant dose of X-rays.

[0023] In one embodiment of the present invention, as shown in Figure 1, we eliminate the use of fluoroscopy. By using ventricular contrast images, the left ventricular contour of the patient's heart in diastole and systole is digitally outlined using a touchscreen, mouse, tablet, or other graphical input device and displayed on a monitor of a separate computer or workstation as both orthogonal views in 2D space, away from the X-ray fluorescence fluoroscopy system and within either the control room of the catheterization facility or a designated area outside the sterile zone. The computer or workstation has an internal modem or network connection device that communicates with the computer of the single-planar X-ray fluorescence fluoroscopy system via an intranet communication link system. The communication link to the network may be of any acceptable type, including, among other things, a telephone line, fiber optic cable, a cable modem link, or a wireless data transfer system. Thus, what is input and displayed on the monitor of the separate computer or workstation is output on the monitor of the single-planar X-ray fluorescence fluoroscopy system, and vice versa. For transendocardial injection of biological agents into a patient's heart, information such as the location of myocardial infarction, areas of motion impairment and akinetic zones, and "non-injectable" zones, as described above, is crucial for identification. This information may be displayed on a monitor within the catheterization facility and will help guide the intervening cardiologist during the procedure. This is done prior to the commencement of the transendocardial injection procedure after mapping the left ventricle in two orthogonal views. Based on the specific requirements of the procedure and therapy, the operator marks these critical zones on a remote computer and clearly defines the areas where injection should and should not be performed on the ventricular angiography in both orthogonal views. These boundaries are made by color coding, the use of solid and dashed lines, and / or the use of different shapes and patterns. As described above, the two orthogonal views help verify the location and orientation of the percutaneous catheter within the left ventricle and verify and mark the injection site. A function or key is used to toggle between the annotated LV contour maps in the two orthogonal views on the remote computer and is displayed on the monitor of the X-ray fluorescence fluoroscopy system.A toggle between two LV contour maps allows the operator to remotely mark the target injection site in each view without having to switch between fluoroscopic images fixed on a monitor of a single-planar X-ray fluoroscopy system within the catheterization facility. Marking the injection site is performed by digitally marking the location of the catheter tip during the transendocardial injection process. If it is an isocenter and the platform is not moved, a single mark should be valid in both views. The marks may have any number of associated fields that are color-coded, have a variable shape or size, and / or record additional information. Site coloring or numbering can then be displayed with an adjustable level of fluoroscopic image, or hidden on the display. They may be grouped so that certain characteristics can be modified for the group rather than for the individual. Several parameters associated with the marked sites may further be displayed on the screen in a separate window. In the latter, the operator can select which parameters they wish to appear adjacent to the marked injection site, as needed, by checking or unchecking the checkboxes associated with such parameters. Examples of these parameters include injection site number, total number of injections, volume of therapeutic agent injected (0.1 ml to 1.0 ml per injection in the case of intramyocardial injection), dose of therapeutic agent delivered (concentration, total number of cells from 1 × 10⁶ to 200 × 10⁶, total amount of plasmid / gene or peptide or protein, total number of particles), timestamp, screen coordinates, ventricular wall thickness or electrophysiological activity at the injection site, the compartment to which the injection is administered based on a 17-compartment bullseye map, its distance from the infarct site, and its distance from other injection sites.

[0024] If a bidirectional fluoroscopy system is available within the catheterization facility, the same capabilities of the software will likely be available. However, since both views are typically projected onto two separate screens mounted on the bidirectional fluoroscopy system, there is no need to toggle from the RAO view to the LAO view. In this case, the two projected fluoroscopic images are independently input into the computer and subsequently output to either one of the two independent displays or two windows on a single display, along with the associated annotations as described above.

[0025] The software interface will also allow the 2D left ventricular image projection, marked injection site, and parameters in any view to be toggled on and off.

[0026] (Example 2: Pre-selected target site)

[0027] In this embodiment, as shown in Figure 2, we describe a second method for selecting target points within a patient's heart for injecting therapeutic agents in transendocardial intramyocardial interventions or for sampling tissue in biopsy procedures. This method follows the same procedure as in Example 1, but the target sites are pre-selected either manually or using various algorithms. These algorithms may be performed by computer and may result in (1) a grid projection uniformly and equally distributed on the endocardial surface, (2) a uniform grid excluding the infarct zone and spaced 0-20 mm away from the infarct zone, (3) a uniform grid within the infarct zone, (4) a uniform grid located distally and equally distributed within the distal 1 / 3 of the ventricular or apical region of the left ventricle, or (5) preferably, a uniformly distributed circular pattern or other functional geometric distribution. Target sites in the range of numbers 1-20 are therefore pre-selected based on a set of parameters required for the specific procedure. In addition to those described in Example 1, these parameters may further include distance from the infarct zone, wall thickness of at least 5 millimeters, distance between injection sites (5 millimeters or more), equally spaced injection sites, injection sites randomly spaced from the infarct zone, and randomly spaced injection sites at a defined distance from the infarct zone, excluding previous sites of therapeutic delivery for transendocardial injection and previous sampling sites for cardiac biopsy. Prior to the day of the procedure, diagnostic cardiac MRI scans, CT scans, and echocardiograms may be used to determine the required pre-defined information, including, but not limited to, wall thickness and location of infarct tissue. On the day of the procedure, prior to the commencement of the procedure, ventricular contrast is performed in both orthogonal views, and the contour of the left ventricle is mapped as described in Example 1. An algorithm selected from the aforementioned list is then executed by a computer, and the target site is pre-selected using predefined parameters and then displayed. Similar to Example 1, the pre-selected target points may be displayed using markers of different shapes, patterns, and / or colors, which can be grouped or ungrouped and toggled on and off.The tip of the puncture element at the distal end of a transendocardial catheter or guided biopsy catheter is then moved to one of the pre-selected target points. Once the injection or sampling is performed, the actual injection site is then marked, and at that point, the pre-selected target point may be hidden or replaced. The marker for the actual injection or sampling marker may have a different shape, pattern, and / or color from the target marker. The new marker may be saved and shaded or hidden before moving to the next pre-selected target point. If the actual target site differs from the pre-selected target site, the algorithm can be applied to readjust the rest of the pre-selected target site based on the parameters applied to the pre-selection. This algorithm is restarted after each injection / sampling to adjust the pre-selected sites as appropriate. Furthermore, if the intervening cardiologist is not satisfied with the pre-selected target sites, the intervening cardiologist can indicate a location they wish to be the first site, which can then be registered by clicking on the new site location in both the RAO and LAO views. The algorithm can then be restarted to modify the remaining locations of the pre-selected target sites for the redefined first site.

[0028] The actual target sites within the patient's left ventricle from which injections are administered are registered and stored. These target points may be displayed along with a set of parameters, including patient identification number, injection number, timestamp, identification of the therapy to be injected, volume injected at the injection site, concentration injected, total dose injected, screen coordinates, wall thickness and / or electrophysiological activity at the injection site, distance from the infarct site to the injection site, distance from the nearest injection site, and the quality or characteristics of contrast agent delivery, either from the base of the puncture element or through the distal puncture element. In cases where sampling is performed, such as in right ventricular cardiac biopsy, the set of parameters may include a previous record of where the sample was taken from the patient's heart, including data related to sample characteristics such as its rejection grade score. This can facilitate the pre-selection of future sampling strategies and algorithms, as discussed in Example 2. Additional parameters may include patient identification number, sample number, timestamp, coordinates of the set of tissue samples taken, wall from which the sample is taken, compartment of a standard 17-compartment cardiac model bullseye plot from which the sample is taken, wall thickness at the sampling site, distance from the sampling site to the infarct location, and, if more than one sample is taken, distance from the nearest sampling site. The quality or characteristics of the contrast agent delivered through the catheter, either from or through the puncture element, using a sampling device or biopsy forceps, including the ability to deliver the contrast agent through either the distal puncture element or the contrast agent port at the base of the biopsy element in the tissue, may also be recorded. Similarly, electrophysiological activity at the sampling site may also be recorded using a sampling device capable of recording bipolar signals.

[0029] (Recording of the target area on the screen - 3D)

[0030] (Example 3)

[0031] Here, as shown in Figure 3, we describe a method for selecting a target point within the patient's left ventricle to inject therapeutic agents in transendocardial intramyocardial interventions or to sample tissue in biopsy procedures. In this method, we combine a 3D cardiac model reconstructed prior to the intervention procedure from cardiac slices obtained using imaging modalities capable of 3D visualization of cardiovascular structures (magnetic resonance imaging, computed tomography, echocardiography) with live fluoroscopic images during catheter placement procedures. After acquiring the patient's ventricle angiography, the 3D model reconstruction of the heart is registered on the orthogonal ventricle angiography and projected onto the live fluoroscopic images. This creates an X-ray projection image combined with an overlay of the registered MR, CT, or echocardiographic images.

[0032] Registration is first achieved by aligning at least two anatomical reference markers on the 3D reconstructed model with corresponding points on the ventricular angiography in two orthogonal views. The initial and all subsequent steps in target point selection are performed on a separate computer or workstation in the control room of the catheterization facility or a designated area, communicating directly with the fluoroscopy system, away from the fluoroscopy system and sterile zone, so that the resulting output can be displayed on the fluoroscopy system's monitor or on a separate monitor visible to the physician. The target injection or sampling area is selected based on procedure selection and exclusion criteria. For example, in the case of transendocardial intramyocardial injection, a wall thickness of 5 mm or less, the location of the infarct, the size of the infarct, the distance from the infarct to the injection site, and the bottom segment of the left ventricular septum can be identified and marked along the 3D surface of the left ventricle on a remote computer and output on the fluoroscopy monitor. Similarly, in the case of tissue sampling for biopsy procedures, the wall thickness, location of the infarct, the size of the infarct, and the previous biopsy sampling site can all be marked. These areas may be indicated by color coding, the use of solid and dashed lines, and / or the use of different shapes and patterns. These boundaries allow the interventional cardiologist to visually identify where therapy should be injected or tissue sampled. During the procedure, the tip of the puncture element at the distal end of the transendocardial injection catheter or guided biopsy catheter is moved to the target point. Using visual recognition, the target point is fixed in 2D space using a target marker on the monitor. The target marker is superimposed on the tip of the puncture element in two orthogonal RAO ​​and LAO views, and when in target recognition mode, the target marker can be forced to advance in 3D space along the endocardium so that it is in the same 3D space as the tip of the puncture element. Registration of the fixed target point and target marker is performed using markers that can take different shapes and can be color-coded. When injection or sampling is performed, registration of the actual injection point is performed by replacing the target point marker with a marker having a different shape and / or color.New markers can be saved and then hidden or shaded before moving to the next target point.

[0033] As in Example 1, when a bidirectional X-ray fluoroscopy system is available in the catheterization facility, both views are typically projected onto two separate screens mounted on the bidirectional X-ray system, eliminating the need to toggle from the RAO view to the LAO view.

[0034] (Example 4)

[0035] In another embodiment, as shown in Figure 4, we describe a method for fitting a 2D cardiac model onto left ventricular angiography in both RAO and LAO views, followed by onto live radiofluoroscopic images. The same steps and the same software capabilities are used, as in Example 2. However, instead of fitting a 3D model of the left ventricular contour, data obtained from cardiac MRI, CT, or echocardiography sections are used prior to the procedure to reconstruct a 2D model of the left ventricle in the same plane as the radiofluoroscopic projection, and the same areas of interest and the aforementioned parameters are marked on the 2D model. These markings are made primarily through the use of color coding, solid and dashed lines, and / or different shapes and patterns, which can be toggled on and off. Otherwise, the selection and registration of the target area are performed in the same manner as described in Examples 1 and 2.

[0036] As in Examples 1 and 2, when a bidirectional X-ray fluoroscopy system is available in the catheterization facility, both views are typically projected onto two separate screens mounted on the bidirectional X-ray system, thus eliminating the need to toggle from the RAO view to the LAO view.

[0037] (Example 5)

[0038] In this embodiment, as shown in Figure 5, we describe a second method for selecting a target site within the patient's left ventricle for administering therapeutic agents in transendocardial intramyocardial interventions or for sampling tissue in biopsy procedures, utilizing multimode fusion imaging. This method follows the same procedure as in Example 3, the difference being that the target sites are pre-selected using a computer algorithm. The computer algorithm is programmed to select a range of 1 to 20 target sites based on a set of parameters required for the specific procedure. In addition to those described in Example 3, these parameters may include distance from the infarct zone, distance between injection sites (5 mm or more), equally spaced injection sites, randomly spaced injection sites from the infarct zone, randomly spaced injection sites at a defined distance from the infarct zone, or predefined electrophysiological activity. Prior to the commencement of the procedure, the target sites are pre-selected using the algorithm and predefined parameters, and they are displayed by the software. Similar to Example 3, the pre-selected target points are displayed using markers of different shapes, patterns, and / or colors, which can be toggled on and off. The tip of the puncture element at the distal end of the transendocardial catheter or guided biopsy catheter is then moved to one of the pre-selected target points. Once the injection or sampling is performed, the actual target point is then registered by replacing the marker markings of the pre-selected target points with new markers of different shapes, patterns, and / or colors. The new markers are saved and can be shaded or hidden before moving to the next pre-selected target point. If the actual target site differs from the pre-selected target site, the algorithm can be applied to readjust the rest of the pre-selected target site based on the parameters applied to the pre-selection. The algorithm is restarted after each injection / sampling to adjust the pre-selected sites as appropriate.Furthermore, if the intervening cardiologist is not satisfied with the pre-selected target sites, they can indicate any desired location as a target, and that target can be registered by clicking on the new site location in both the RAO and LAO views, and the algorithm can then be restarted to modify the remaining locations of the pre-selected target sites relative to the first one.

[0039] In these embodiments, target points within the left ventricle of the patient to whom the injection was administered are registered and stored. These target points can be displayed along with a set of parameters, including patient identification number, injection number, timestamp, identification of the therapeutic injection, volume injected at the injection site, concentration injected, total dose injected, screen coordinates, wall thickness at the injection site, electrophysiological activity, distance from the infarct location to the injection site, and distance from the nearest injection site. If sampling is performed, the set of parameters may include patient identification number, sample number, timestamp, coordinates of the set from which the tissue was sampled, the wall from which the sample was taken, the compartment of a standard 17-compartment cardiac model bullseye plot from which the sample was taken, wall thickness at the sampling site, electrophysiological activity, distance from the infarct location to the sampling site, and, if more than one sample was taken, the distance from the nearest sampling site.

[0040] The foregoing is a complete description of preferred embodiments of the present invention, but various substitutions, modifications, and equivalents may be used. Therefore, the foregoing description should not be taken as a limitation of the scope of the present invention as defined by the appended claims.

Claims

1. An imaging system for transendocardial delivery to a patient's heart and / or biopsy of the heart, wherein the imaging system is Image processing means configured to receive two orthogonal two-dimensional images, wherein the two orthogonal two-dimensional images are fluorescence fluoroscopy images of the patient's heart, and the image processing means is further configured to generate a combined three-dimensional model reconstruction of the heart by transposing a preoperative three-dimensional model obtained by computed tomography or magnetic resonance imaging of the patient's heart onto the two orthogonal two-dimensional images, wherein transposition includes aligning the preoperative three-dimensional model with the two orthogonal two-dimensional images by aligning the preoperative three-dimensional model with one or more anatomical features represented in the preoperative three-dimensional model and the two orthogonal two-dimensional images, and projecting the aligned preoperative three-dimensional model as a visual overlay onto the two orthogonal two-dimensional images on a display in or adjacent to the sterile field, wherein the combined three-dimensional model reconstruction includes the preoperative three-dimensional model aligned with and superimposed on the two orthogonal two-dimensional images, the image processing means The image processing means is equipped with, To guide the tip of the transendocardial catheter, the position of the tip of the transendocardial catheter relative to one or more anatomical structures represented on the combined three-dimensional model reconstruction is displayed, The method involves recording one or more locations of transendocardial delivery and / or biopsy of cardiac tissue on the two orthogonal two-dimensional images, wherein the one or more locations are aligned and stored on the two orthogonal two-dimensional images, and the recorded one or more locations are configured to remain visible on the combined three-dimensional model as the transendocardial catheter is advanced to perform subsequent transendocardial delivery and / or biopsy at additional locations. An image processing system further configured to perform the following actions.

2. A system for transendocardial injection and / or biopsy of a patient's heart, wherein the system is The transendocardial catheter is configured to inject a therapeutic agent and / or biopsy cardiac tissue into one or more target sites of the heart, The transendocardial catheter is configured to be guided to one or more target sites using guidance means, The guidance means comprises an image processing means configured to receive two orthogonal two-dimensional images, the two orthogonal two-dimensional images being fluorescence fluoroscopy images of the patient's heart, and the image processing means is further configured to generate a combined three-dimensional model reconstruction of the heart by transposing a preoperative three-dimensional model obtained by computed tomography or magnetic resonance imaging of the patient's heart onto the two orthogonal two-dimensional images, the transposition including aligning the preoperative three-dimensional model with the two orthogonal two-dimensional images by aligning the preoperative three-dimensional model with the anatomical features represented in the preoperative three-dimensional model and the two orthogonal two-dimensional images, and projecting the aligned preoperative three-dimensional model as a visual overlay onto the two orthogonal two-dimensional images on a display in or adjacent to the sterile field, the combined three-dimensional model reconstruction including the preoperative three-dimensional model aligned with and superimposed on the two orthogonal two-dimensional images. The aforementioned image processing means is To guide the tip of the transendocardial catheter, the position of the tip of the transendocardial catheter relative to one or more anatomical structures represented on the combined three-dimensional model reconstruction is displayed, The method involves recording one or more locations of transendocardial delivery and / or biopsy of cardiac tissue on the two orthogonal two-dimensional images, wherein the one or more locations are aligned and stored on the two orthogonal two-dimensional images, and the recorded one or more locations are configured to remain visible on the combined three-dimensional model as the transendocardial catheter is advanced to perform subsequent transendocardial delivery and / or biopsy at additional locations. A system further configured to perform the following actions.

3. The image processing system according to claim 1 or the system according to claim 2, wherein the image processing means for generating a combined three-dimensional model reconstruction of the heart by transposing a preoperative three-dimensional model onto two orthogonal two-dimensional images comprises means for aligning at least two anatomical features of the combined three-dimensional model reconstruction of the heart with corresponding points on the two orthogonal two-dimensional images.

4. The image processing means is further configured to mark and display one or more target regions for transendocardial delivery and / or biopsy on the combined three-dimensional model reconstruction of the heart using corresponding points on the two orthogonal two-dimensional images, wherein the target regions are selected based on procedure selection and exclusion criteria including one or more of the following: wall thickness, myocardial infarction location, myocardial infarction size, distance from myocardial infarction, immobile region, akinetic region, distance between one or more target sites, one or more equally spaced target sites, one or more target sites randomly spaced from myocardial infarction, one or more target sites randomly spaced at a defined distance from myocardial infarction, distance from myocardial infarction to one or more target sites and the bottom segment of the left ventricular septum, site of therapeutic delivery for transendocardial injection, sampling site for cardiac biopsy, or predefined electrophysiological activity, as described in claim 1 or claim 2.

5. The image processing system or system according to claim 4, wherein the one or more target regions are selected using a computer algorithm based on parameters including one or more of the following: wall thickness, location of myocardial infarction, size of myocardial infarction, distance from myocardial infarction, immobile region, akinetic region, distance between one or more target sites, one or more equally spaced target sites, one or more target sites randomly spaced from myocardial infarction, one or more target sites randomly spaced at a defined distance from myocardial infarction, distance from myocardial infarction to one or more target sites and the bottom segment of the left ventricular septum, site of therapeutic delivery for transendocardial injection, sampling site for cardiac biopsy, or predefined electrophysiological activity.

6. An imaging system for transendocardial delivery to a patient's heart and / or biopsy of the heart, wherein the imaging system is Image processing means configured to receive two orthogonal two-dimensional images, wherein the two orthogonal two-dimensional images are fluorescence fluoroscopy images of the patient's heart, and the image processing means is further configured to generate a combined three-dimensional model reconstruction of the heart by transposing a preoperative three-dimensional model onto the two orthogonal two-dimensional images, wherein transposition includes aligning the preoperative three-dimensional model with the two orthogonal two-dimensional images by aligning the biological structure, and projecting the aligned preoperative three-dimensional model as a visual overlay onto the two orthogonal two-dimensional images on a display within or adjacent to the sterile field, wherein the combined three-dimensional model reconstruction includes the preoperative three-dimensional model aligned with and superimposed on the two orthogonal two-dimensional images, the image processing means The image processing means superimposes information indicating to the operator one or more target areas or regions to be avoided onto the combined three-dimensional model reconstruction of the patient's heart. The aforementioned image processing means is To guide the tip of the transendocardial catheter, the position of the tip of the transendocardial catheter relative to one or more target sites or regions represented on the combined three-dimensional model reconstruction is displayed, The method involves recording one or more locations of transendocardial delivery and / or biopsy of cardiac tissue on the two orthogonal two-dimensional images, wherein the one or more locations are aligned and stored on the two orthogonal two-dimensional images, and the recorded one or more locations are configured to remain visible on the combined three-dimensional model as the transendocardial catheter is advanced to perform subsequent transendocardial delivery and / or biopsy at additional locations. An image processing system further configured to perform the following actions.

7. The image processing system according to claim 6, for generating a combined three-dimensional model reconstruction of the heart by transposing a preoperative three-dimensional model onto two orthogonal two-dimensional images, comprising means for aligning at least two anatomical reference markers on the combined three-dimensional model reconstruction of the heart with corresponding points on the two orthogonal two-dimensional images.

8. The image processing means is further configured to mark and display one or more target regions for transendocardial delivery and / or biopsy on the combined three-dimensional model reconstruction of the heart using corresponding points on the two orthogonal two-dimensional images, wherein the target regions are selected based on procedure selection and exclusion criteria including one or more of the following: wall thickness, myocardial infarction location, myocardial infarction size, distance from myocardial infarction, immobile region, akinetic region, distance between one or more target sites, one or more equally spaced target sites, one or more target sites randomly spaced from myocardial infarction, one or more target sites randomly spaced at a defined distance from myocardial infarction, distance from myocardial infarction to one or more target sites and the bottom segment of the left ventricular septum, site of therapeutic delivery for transendocardial injection, sampling site for cardiac biopsy, or predefined electrophysiological activity.

9. The image processing system according to claim 8, wherein the one or more target regions are selected using a computer algorithm based on parameters including one or more of the following: wall thickness, location of myocardial infarction, size of myocardial infarction, distance from myocardial infarction, immobility region, akinesia region, distance between one or more target sites, one or more equally spaced target sites, one or more target sites randomly spaced from myocardial infarction, one or more target sites randomly spaced at a defined distance from myocardial infarction, distance from myocardial infarction to one or more target sites and the bottom segment of the left ventricular septum, site of therapeutic delivery for transendocardial injection, sampling site for cardiac biopsy, or predefined electrophysiological activity.

10. The image processing system according to claim 6, wherein the image processing means for superimposing information onto the combined three-dimensional model reconstruction of the heart is configured to generate one or more marks or annotations on the combined three-dimensional model reconstruction or the two orthogonal two-dimensional images.

11. The image processing system according to claim 10, wherein the one or more marks or annotations include one or more of anatomical information, treatment information, markers, color coding, outlines, borders, written information, or icons.

Images