Systems, devices, and methods for cardiac source modeling

Abstract

Provided are action potential mapping systems, devices, and methods. An action potential mapping system comprises: a processor for performing an algorithm; a plurality of electrodes, the plurality of electrodes being operatively coupled to the processor and the patient; and a non-transitory computer readable medium storing instructions for the processor to perform the algorithm. The algorithm is configured to estimate action potentials, each representative of a plurality of cells.

Description

[0001] SYSTEMS, DEVICES, AND METHODS FOR CARDIAC SOURCE MODELING

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003]

[0001] This application claims the benefit of United States Provisional Application Serial

[0004] Number 63 / 545,194 (Docket No. ENC-002-PR1), titled “Cardiac Source Modeling and its Applications in Cardiac Mapping”, filed October 22, 2023; and is a Continuation-in-Part of International PCT Patent Application Serial Number PCT / US2024 / 030585 (Docket No. ENC- 001-PCT), titled “Mapping and Navigation System” filed May 22, 2024; which claims the benefit of United States Provisional Application Serial Number 63 / 503,665 (Docket No.: ENC- 001-PR1), titled “Basket Catheter Comprised of Flex Circuits with Electrodes on Both Sides of the Splines”, filed May 22, 2023; and which claims the benefit of United States Provisional Application Serial Number 63 / 506,314 (Docket No.: ENC-001-PR2), titled “Hybrid Navigation of the Catheter Using Both Magnetic and Impedance Fields”, filed June 5, 2023; the contents of all of the foregoing being herewith incorporated by reference in their entireties.

[0005] FIELD OF THE INVENTIVE CONCEPTS

[0006]

[0002] The present inventive concepts relate generally to systems, devices, and methods for diagnosing cardiac disease, and in particular mapping cardiac electrical activity.

[0007] BACKGROUND

[0008]

[0003] Several medical procedures include treating cardiac disease using catheter devices that are inserted proximate the heart of a patient (e.g., inserted into a heart chamber). Identifying diseased tissue and tracking the location and orientation of various devices used to identify and / or treat the tissue can be difficult, and this difficulty can cause poor clinical results.

[0009]

[0004] There is a need for systems, methods, and devices that improve diagnosis and treatment of cardiac disease.

[0010] SUMMARY

[0011]

[0005] According to an aspect of the present inventive concepts, an action potential mapping system comprises: a processor for performing an algorithm; a plurality of electrodes, the plurality of electrodes being operatively coupled (e.g., electrically coupled) to the processor and the patient; and a non-transitory computer readable medium storing instructions for the processor to perform the algorithm. The algorithm is configured to estimate action potentials, each representative of a plurality of cells, by: (a) receiving inputs of a heart chamber anatomy of a patient and spatial coordinates of the plurality of electrodes, and performing forward modeling to produce a lead field; (b) receiving the lead field and receiving a respective plurality of voltage values corresponding to respective voltages detected at the plurality of electrodes; (c) creating an action potential shape model; and (d) performing an inverse solution to produce a plurality of values representing the estimated action potentials.

[0012]

[0006] In some embodiments, the plurality of electrodes comprises a first plurality of electrodes and a second plurality of electrodes, and the first plurality of electrodes are configured to be disposed on respective skin regions of the patient, and the second plurality of electrodes are configured to be disposed within the patient (e.g., within the heart or other internal body location).

[0013]

[0007] In some embodiments, the plurality of electrodes comprises an electrode array assembly including one, two, or more electrodes of the plurality of electrodes. The electrode array assembly can comprise at least one support member, and the at least one support member can be constructed and arranged to support the one, two, or more electrodes in a generally ellipsoidal configuration.

[0014]

[0008] In some embodiments, the processor comprises a non-transitory computer.

[0015]

[0009] In some embodiments, the system can further comprise a signal processor, and the signal processor can be operatively coupled (e.g., electrically coupled) between the plurality of electrodes and the processor.

[0016]

[0010] In some embodiments, the spatial coordinates of the plurality of electrodes are derived from magnetic navigation (e.g., via a magnetic navigation module of the system), impedance navigation (e.g., via an impedance navigation module of the system), or both.

[0017]

[0011] In some embodiments, at least a part of the processor is disposed remotely from the plurality of electrodes.

[0018]

[0012] In some embodiments, the plurality of cells comprises a plurality of cardiac cells. The plurality of cardiac cells can comprise a plurality of human cardiac cells.

[0013] In some embodiments, the plurality of cells comprises a cell type (e.g., a mammalian cell type) selected from the group consisting of: a bladder cell; a brain cell; a peripheral nerve cell; and combinations thereof.

[0019]

[0014] In some embodiments, the system further comprises an anatomy module, and the anatomy module can be configured to generate patient geometry data.

[0020]

[0015] In some embodiments, the plurality of electrodes are spaced apart from one another at a respective distance of no more than 5mm, 3mm, and / or 1mm.

[0021]

[0016] In some embodiments, the plurality of electrodes are spaced apart from one another at a respective distance of at least 1mm, 3 mm, and / or 5 mm.

[0022]

[0017] In some embodiments, the system further comprises a plurality of magnetic sensors, and the plurality of magnetic sensors can be operatively coupled (e.g., electrically coupled) to the processor.

[0023]

[0018] According to another aspect of the present inventive concepts, an action potential mapping system comprises: a processor for performing an algorithm; a plurality of electrodes, the plurality of electrodes being operatively coupled (e.g., electrically coupled) to the processor and the patient; and a non-transitory computer readable medium storing instructions for the processor to perform the algorithm. The algorithm can be configured to estimate action potentials, each representative of a plurality of cells, by: (a) receiving inputs of a heart chamber anatomy of a patient and spatial coordinates of a plurality of electrodes coupled to the patient, and performing forward modeling to produce a lead field; (b) receiving the lead field and receiving a respective plurality of voltage values corresponding to respective voltages detected at the plurality of electrodes; and (c) performing an inverse solution to produce a plurality of values representing the estimated action potentials. The producing of the lead field can include developing a forward model:

[0024] Y - AS where S denotes a matrix containing a discretized action potential of a cardiac surface and / or other tissue surface, Y denotes a measurement matrix, forward model matrix A denotes the lead field. The lead field can be derived by the equation: where V m r ' ;t is an unknown action potential, and V r;t is a measured voltage at the electrode located at r and time t. The inverse solution can include: (i) reconstructing a shape of a cardiac action potential and / or other action potential by parameterizing the action potential according to: where α, β , γ are constants defining the steepness of the upstroke and downstroke, δ is the timing of local depolarization, ρ is the timing of local repolarization, and τ is the translation parameter; (ii) applying the lead field and the plurality of voltage values; (iii) creating a map of estimated action potentials; (iv) for each point within the action potential map, updating values for slope parameters, translation estimation, local depolarization times and local repolarization times; (v) updating the action potential estimations; and (vi) iterating until convergence to produce the plurality of values representing the estimated action potentials.

[0025]

[0019] In some embodiments, the plurality of electrodes comprises a first plurality of electrodes and a second plurality of electrodes, and the first plurality of electrodes are configured to be disposed on respective skin regions of the patient, and the second plurality of electrodes are configured to be disposed within the patient (e.g., within the heart or other internal body location).

[0026]

[0020] In some embodiments, the plurality of electrodes comprises an electrode array assembly including one, two, or more electrodes of the plurality of electrodes. The electrode array assembly can comprise at least one support member, and the at least one support member can be constructed and arranged to support the one, two, or more electrodes in a generally ellipsoidal configuration.

[0027]

[0021] In some embodiments, the processor comprises a non-transitory computer.

[0028]

[0022] In some embodiments, the system can further comprise a signal processor, and the signal processor can be operatively coupled (e.g., electrically coupled) between the plurality of electrodes and the processor.

[0029]

[0023] In some embodiments, at least a part of the processor is disposed remotely from the plurality of electrodes.

[0030]

[0024] In some embodiments, the plurality of cells comprises a plurality of cardiac cells. The plurality of cardiac cells can comprise a plurality of human cardiac cells.

[0025] In some embodiments, the plurality of cells comprises a cell type (e.g., a mammalian cell type) selected from the group consisting of: a bladder cell; a brain cell; a peripheral nerve cell; and combinations thereof.

[0031]

[0026] In some embodiments, the system can further comprise an anatomy module, and the anatomy module can be configured to generate patient geometry data.

[0032]

[0027] In some embodiments, the plurality of electrodes are spaced apart from one another at a respective distance of no more than 5mm, 3mm, and / or 1mm.

[0033]

[0028] In some embodiments, the plurality of electrodes are spaced apart from one another at a respective distance of at least 1mm, 3mm, and / or 5mm.

[0034]

[0029] In some embodiments, the system further comprises a plurality of magnetic sensors, and the plurality of magnetic sensors can be operatively coupled (e.g., electrically coupled) to the processor.

[0035]

[0030] According to another aspect of the present inventive concepts, an action potential mapping system comprises: a processor for performing an algorithm; a plurality of electrodes, the plurality of electrodes being operatively coupled (e.g., electrically coupled) to the processor and the patient; and a non-transitory computer readable medium storing instructions for the processor to perform the algorithm. The algorithm can be configured to estimate an action potential representative of a plurality of cells by: (a) receiving inputs of a heart chamber anatomy of a patient and spatial locations of a plurality of electrodes coupled to the patient, and performing forward modeling to produce a lead field; (b) receiving the lead field and receiving a respective plurality of voltage values corresponding to respective voltages detected at the plurality of electrodes; and (c) performing an inverse solution to produce a plurality of values representing the estimated action potentials. The producing of the lead field can include developing a forward model: where S denotes a matrix containing a discretized action potential of the cardiac surface and / or other tissue surface, denotes a 3m xt matrix containing the directional derivative of measurements Y with respect to x, y, and z, and forward model matrix A denotes the lead field. The lead field can be derived by the equation: where V m r ' ;t is an unknown action potential, and V r;t is the measured voltage at the electrode located at r and time t. The inverse solution can include: (i) reconstructing a shape of a cardiac action potential and / or other action potential by parameterizing the action potential according to: where α, β , γ are constants defining the steepness of the upstroke and downstroke, δ is the timing of local depolarization, p is the timing of local repolarization, and τ is the translation parameter; (ii) applying the lead field and the plurality of voltage values; (iii) estimating an action potential map; (iv) for each point within the action potential map, updating values for slope parameters, translation estimation, local depolarization times and local repolarization times; (v) updating the action potential estimations; and (vi) iterating until convergence to produce the plurality of values representing the estimated action potentials.

[0036]

[0031] In some embodiments, the plurality of electrodes comprises a first plurality of electrodes and a second plurality of electrodes, and the first plurality of electrodes are configured to be disposed on respective skin regions of the patient, and the second plurality of electrodes are configured to be disposed within the patient (e.g., within the heart or other internal body location).

[0037]

[0032] In some embodiments, the plurality of electrodes comprises an electrode array assembly including one, two, or more electrodes of the plurality of electrodes. The electrode array assembly can comprise at least one support member, and the at least one support member can be constructed and arranged to support the one, two, or more electrodes in a generally ellipsoidal configuration.

[0038]

[0033] In some embodiments, the processor comprises a non-transitory computer.

[0039]

[0034] In some embodiments, the system further comprises a signal processor, and the signal processor can be operatively coupled (e.g., electrically coupled) between the plurality of electrodes and the processor.

[0040]

[0035] In some embodiments, at least a part of the processor is disposed remotely from the plurality of electrodes

[0036] In some embodiments, the plurality of cells comprises a plurality of cardiac cells. The plurality of cardiac cells can comprise a plurality of human cardiac cells.

[0041]

[0037] In some embodiments, the plurality of cells comprises a cell type (e.g., a mammalian cell type) selected from the group consisting of: a bladder cell; a brain cell; a peripheral nerve cell; and combinations thereof.

[0042]

[0038] In some embodiments, the system can further comprise an anatomy module, and the anatomy module can be configured to generate patient geometry data.

[0043]

[0039] In some embodiments, the plurality of electrodes are spaced apart from one another at a respective distance of no more than 5mm, 3mm, and / or 1mm.

[0044]

[0040] In some embodiments, the plurality of electrodes are spaced apart from one another at a respective distance of at least 1mm, 3mm, and / or 5mm.

[0045]

[0041] In some embodiments, the system further comprises a plurality of magnetic sensors, and the plurality of magnetic sensors can be operatively coupled (e.g., electrically coupled) to the processor.

[0046]

[0042] The technology described herein, along with the attributes and attendant advantages thereof, will best be appreciated and understood in view of the following detailed description taken in conjunction with the accompanying drawings in which representative embodiments are described by way of example.

[0047] INCORPORATION BY REFERENCE

[0048]

[0043] 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. The content of all publications, patents, and patent applications mentioned in this specification are herein incorporated by reference in their entirety for all purposes.

[0049] BRIEF DESCRIPTION OF THE DRAWINGS

[0050]

[0044] Fig. 1 illustrates a block diagram of an embodiment of a diagnostic mapping system, consistent with the present inventive concepts.

[0051]

[0045] Fig. 1A illustrates a block diagram of another embodiment of a diagnostic mapping system, consistent with the present inventive concepts.

[0046] Fig.2 illustrates a side view of an embodiment of a catheter including a handle and a functional assembly, consistent with the present inventive concepts.

[0052]

[0047] Fig.3 illustrates a perspective view of the distal portion of an embodiment of a catheter including a basket-like functional assembly, consistent with the present inventive concepts.

[0053]

[0048] Fig.4 illustrates a side view of the distal portion of an embodiment of a catheter including a basket-like functional assembly, consistent with the present inventive concepts.

[0054]

[0049] Fig. 4A illustrates a cross-sectional view of the functional assembly of Fig. 3, consistent with the present inventive concepts.

[0055]

[0050] Figs.5A and 5B illustrate anatomic views showing embodiments of patch electrodes placement arrangements, consistent with the present inventive concepts.

[0056]

[0051] Figs.6 and 7 each illustrate an anatomical model with appropriately positioned system components and a flow chart of a method of cardiac source mapping, consistent with the present inventive concepts.

[0057]

[0052] Fig.8 illustrates a graph of multiple cardiac activations, consistent with the present inventive concepts.

[0058]

[0053] Fig.9 illustrates a graph of two action potentials of different durations, consistent with the present inventive concepts.

[0059]

[0054] Figs. 10 through 13 illustrate graphs of various models of action potentials, consistent with the present inventive concepts.

[0060]

[0055] Fig. 14 illustrates a flow chart of a series of steps configured to estimate one or more action potentials, consistent with the present inventive concepts.

[0061]

[0056] Fig. 15 illustrates a flow chart of another series of steps configured to estimate one or more action potentials, consistent with the present inventive concepts.

[0062]

[0057] Fig. 16 illustrates a flow chart of an approach for estimating cardiac action potentials, consistent with the present inventive concepts.

[0063] DETAILED DESCRIPTION OF THE DRAWINGS

[0064]

[0058] Reference will now be made in detail to the present embodiments of the technology, examples of which are illustrated in the accompanying drawings. Similar reference numbers may be used to refer to similar components. However, the description is not intended to limit the present disclosure to particular embodiments, and it should be construed as including various modifications, equivalents, and / or alternatives of the embodiments described herein.

[0065]

[0059] It will be understood that the words "comprising" (and any form of comprising, such as "comprise" and "comprises"), "having" (and any form of having, such as "have" and "has"), "including" (and any form of including, such as "includes" and "include") or "containing" (and any form of containing, such as "contains" and "contain") when used herein, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0066]

[0060] It will be further understood that, although the terms first, second, third, etc. may be used herein to describe various limitations, elements, components, regions, layers and / or sections, these limitations, elements, components, regions, layers and / or sections should not be limited by these terms. These terms are only used to distinguish one limitation, element, component, region, layer or section from another limitation, element, component, region, layer or section. Thus, a first limitation, element, component, region, layer or section discussed below could be termed a second limitation, element, component, region, layer or section without departing from the teachings of the present application.

[0067]

[0061] It will be further understood that when an element (also referred to as a “component” herein) is described as being "on", "attached", "connected" or "coupled" to another element, it can be directly on or above, or connected or coupled to, the other element, or one or more intervening elements can be present. In contrast, when an element is referred to as being "directly on", "directly attached", "directly connected" or "directly coupled" to another element, there are no intervening elements present. Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g. "between" versus "directly between," "adjacent" versus "directly adjacent," etc.).

[0068]

[0062] As used herein, the terms “operably attached”, “operably connected”, “operatively coupled” and similar terms related to attachment of components shall refer to attachment of two or more components that results in one, two, or more of: electrical attachment; fluid attachment; magnetic attachment; mechanical attachment; optical attachment; sonic attachment; and / or other operable attachment arrangements. The operable attachment of two or more components can facilitate the transmission between the two or more components of: power; signals; electrical energy; fluids or other flowable materials; magnetism; mechanical linkages; light; sound such as ultrasound; and / or other materials and / or components.

[0069]

[0063] It will be further understood that when a first element is referred to as being "in”, "on" and / or "within” a second element, the first element can be positioned: within an internal space of the second element, within a portion of the second element (e.g. within a wall of the second element); positioned on an external and / or internal surface of the second element; and combinations of one or more of these.

[0070]

[0064] As used herein, the term “proximate”, when used to describe proximity of a first component or location to a second component or location, is to be taken to include one or more locations near to the second component or location, as well as locations in, on and / or within the second component or location. For example, a component positioned proximate an anatomical site (e.g. a blood or other fluid delivery location), shall include components positioned near to the anatomical site, as well as components positioned in, on and / or within the anatomical site.

[0071]

[0065] Spatially relative terms, such as "beneath,” "below,” "lower," "above," "upper", “under” and the like may be used to describe an element and / or feature's relationship to another element(s) and / or feature(s) as, for example, illustrated in the figures. It will be further understood that the spatially relative terms are intended to encompass different orientations of the device in use and / or operation in addition to the orientation depicted in the figures. For example, if the device in a figure is turned over, elements described as ''below” and / or "beneath" other elements or features would then be oriented "above" the other elements or features. The device can be otherwise oriented (e.g. rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.

[0072]

[0066] The terms “reduce”, “reducing”, “reduction” and the like, where used herein, are to include a reduction in a quantity, including a reduction to zero. Reducing the likelihood of an occurrence shall include prevention of the occurrence. Correspondingly, the terms “prevent”, “preventing”, and “prevention” shall include the acts of “reduce”, “reducing”, and “reduction”, respectively.

[0073]

[0067] The term "and / or" where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example "A and / or B" is to be taken as specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each is set out individually herein.

[0068] The term “one or more”, where used herein can mean one, two, three, four, five, six, seven, eight, nine, ten, or more, up to any number.

[0074]

[0069] The terms “and combinations thereof’ and “and combinations of these” can each be used herein after a list of items that are to be included singly or collectively. For example, a component, process, and / or other item selected from the group consisting of: A; B; C; and combinations thereof, shall include a set of one or more components that comprise: one, two, three or more of item A; one, two, three or more of item B; and / or one, two, three, or more of item C.

[0075]

[0070] In this specification, unless explicitly stated otherwise, “and” can mean “or”, and “or” can mean “and”. For example, if a feature is described as having A, B, or C, the feature can have

[0076] A, B, and C, or any combination of A, B, and C. Similarly, if a feature is described as having A,

[0077] B, and C, the feature can have only one or two of A, B, or C.

[0078]

[0071] As used herein, when a quantifiable parameter is described as having a value “between” a first value X and a second value Y, it shall include the parameter having a value of: at least X, no more than Y, and / or at least X and no more than Y. For example, a length of between 1 and 10 shall include a length of at least 1 (including values greater than 10), a length of less than 10 (including values less than 1), and / or values greater than 1 and less than 10.

[0079]

[0072] The expression “configured (or set) to” used in the present disclosure may be used interchangeably with, for example, the expressions “suitable for”, “having the capacity to”, “designed to”, “adapted to”, “made to” and “capable of’ according to a situation. The expression “configured (or set) to” does not mean only “specifically designed to” in hardware.

[0080] Alternatively, in some situations, the expression “a device configured to” may mean that the device “can” operate together with another device or component.

[0081]

[0073] As used herein, the terms “about” or “approximately” shall refer to ± 20% of a stated value.

[0082]

[0074] As used herein, the term “threshold” refers to a maximum level, a minimum level, and / or range of values correlating to a desired or undesired state. In some embodiments, a system parameter is maintained above a minimum threshold, below a maximum threshold, within a threshold range of values, and / or outside a threshold range of values, such as to cause a desired effect (e.g. efficacious therapy) and / or to prevent or otherwise reduce (hereinafter “prevent”) an undesired event (e.g. a device and / or clinical adverse event). In some embodiments, a system parameter is maintained above a first threshold (e.g. above a first temperature threshold to cause a desired therapeutic effect to tissue) and below a second threshold (e.g. below a second temperature threshold to prevent undesired tissue damage). In some embodiments, a threshold value is determined to include a safety margin, such as to account for patient, user, and / or operator variability, system variability, tolerances, and the like. As used herein, “exceeding a threshold” relates to a parameter going above a maximum threshold, below a minimum threshold, within a range of threshold values and / or outside of a range of threshold values.

[0083]

[0075] As described herein, “room pressure” shall mean pressure of the environment surrounding the systems and devices of the present inventive concepts. Positive pressure includes pressure above room pressure or simply a pressure that is greater than another pressure, such as a positive differential pressure across a fluid pathway component such as a valve. Negative pressure includes pressure below room pressure or a pressure that is less than another pressure, such as a negative differential pressure across a fluid component pathway such as a valve. Negative pressure can include a vacuum but does not imply a pressure below a vacuum. As used herein, the term “vacuum” can be used to refer to a full or partial vacuum, or any negative pressure as described hereabove.

[0084]

[0076] The term “diameter” where used herein to describe a non-circular geometry is to be taken as the diameter of a hypothetical circle approximating the geometry being described. For example, when describing a cross section, such as the cross section of a component, the term “diameter” shall be taken to represent the diameter of a hypothetical circle with the same cross sectional area as the cross section of the component being described.

[0085]

[0077] The terms “major axis” and “minor axis” of a component where used herein are the length and diameter, respectively, of the smallest volume hypothetical cylinder which can completely surround the component.

[0086]

[0078] As used herein, the term “functional element” is to be taken to include one or more elements constructed and arranged to perform a function. A functional element can comprise a sensor and / or a transducer. In some embodiments, a functional element is configured to deliver energy. In some embodiments, a functional element is configured to treat tissue (e.g. a functional element configured as a treatment element). Alternatively or additionally, a functional element (e.g. a functional element comprising a sensor) can be configured to record one or more parameters, such as a patient physiologic parameter; a patient anatomical parameter (e.g. a tissue geometry parameter); a patient environment parameter; and / or a system parameter. In some embodiments, a sensor or other functional element is configured to perform a diagnostic function (e.g. to gather data used to perform a diagnosis). In some embodiments, a functional element is configured to perform a therapeutic function (e.g. to deliver therapeutic energy and / or a therapeutic agent). In some embodiments, a functional element comprises one or more elements constructed and arranged to perform a function selected from the group consisting of: deliver energy; extract energy (e.g. to cool a component); deliver a drug or other agent; manipulate a system component or patient tissue; record or otherwise sense a parameter such as a patient physiologic parameter or a system parameter; and combinations of one or more of these. A functional element can comprise a fluid and / or a fluid delivery system. A functional element can comprise a reservoir, such as an expandable balloon or other fluid-maintaining reservoir. A “functional assembly” can comprise an assembly constructed and arranged to perform a function, such as a diagnostic and / or therapeutic function. A functional assembly can comprise an expandable assembly. A functional assembly can comprise one or more functional elements.

[0079] The term “transducer” where used herein is to be taken to include any component or combination of components that receives energy or any input, and produces an output. For example, a transducer can include an electrode that receives electrical energy, and distributes the electrical energy to tissue (e.g. based on the size of the electrode). In some configurations, a transducer converts an electrical signal into any output, such as: light (e.g. a transducer comprising a light emitting diode or light bulb), sound (e.g. a transducer comprising a piezo crystal configured to deliver ultrasound energy); pressure (e.g. an applied pressure or force); heat energy; cryogenic energy; chemical energy; mechanical energy (e.g. a transducer comprising a motor or a solenoid); magnetic energy; and / or a different electrical signal (e.g. different than the input signal to the transducer). Alternatively or additionally, a transducer can convert a physical quantity (e.g. variations in a physical quantity) into an electrical signal. A transducer can include any component that delivers energy and / or an agent to tissue, such as a transducer configured to deliver one or more of: electrical energy to tissue (e.g. a transducer comprising one or more electrodes); light energy to tissue (e.g. a transducer comprising a laser, light emitting diode and / or optical component such as a lens or prism); mechanical energy to tissue (e.g. a transducer comprising a tissue manipulating element); sound energy to tissue (e.g. a transducer comprising a piezo crystal); chemical energy; electromagnetic energy; magnetic energy; and combinations of one or more of these.

[0087]

[0080] As used herein, the term “fluid” can refer to a liquid, gas, gel, or any flowable material, such as a material which can be propelled through a lumen and / or opening.

[0088]

[0081] As used herein, the term “material” can refer to a single material, or a combination of two, three, four, or more materials.

[0089]

[0082] As used herein, the term “user interface” can comprise one or more interfaces, each interface comprising one or more components configured to receive an input from a user, “user input device” herein, and / or one or more components configured to provide output to a user, “user output device” herein.

[0090]

[0083] The terms “data” and “information” are used interchangeably herein.

[0091]

[0084] It is appreciated that certain features of the inventive concepts, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the inventive concepts which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination. For example, it will be appreciated that all features set out in any of the claims (whether independent or dependent) can be combined in any given way.

[0092]

[0085] It is to be understood that at least some of the figures and descriptions of the inventive concepts have been simplified to focus on elements that are relevant for a clear understanding of the inventive concepts, while eliminating, for purposes of clarity, other elements that those of ordinary skill in the art will appreciate may also comprise a portion of the inventive concepts. However, because such elements are well known in the art, and because they do not necessarily facilitate a better understanding of the inventive concepts, a description of such elements is not provided herein.

[0093]

[0086] Terms defined in the present disclosure are only used for describing specific embodiments of the present disclosure and are not intended to limit the scope of the present disclosure. Terms provided in singular forms are intended to include plural forms as well, unless the context clearly indicates otherwise. All of the terms used herein, including technical or scientific terms, have the same meanings as those generally understood by an ordinary person skilled in the related art, unless otherwise defined herein. Terms defined in a generally used dictionary should be interpreted as having meanings that are the same as or similar to the contextual meanings of the relevant technology and should not be interpreted as having ideal or exaggerated meanings, unless expressly so defined herein. In some cases, terms defined in the present disclosure should not be interpreted to exclude the embodiments of the present disclosure.

[0094]

[0087] Provided herein are systems, devices, and methods for diagnosing cardiac disease, such as by mapping cardiac electrical activity to identify undesired conduction pathways. A catheter comprising a functional assembly can include one or more electrodes for recording cardiac electrical activity. The catheter can include one or more magnetic sensors for localizing the catheter within the patient. The system can include a console for operating the catheter, where the console comprises a diagnostic module for recording signals from the one or more electrodes and a processing unit for processing the recorded signals.

[0095]

[0088] Referring now to Fig. 1, a block diagram of an embodiment of a diagnostic mapping system is illustrated, consistent with the present inventive concepts. System 10 can be configured to map electric magnitudes, morphologies, conduction pathways, physiologic states, and / or other electrical properties or activity within the cardiac tissue of a patient (“electrical activity” herein). System 10 can be configured to perform cardiac source modeling, such as when configured as an action potential mapping system, such as a system configured to estimate one or more action potentials, each action potential representative of one or more cells (e.g., a plurality of cells), such as one or more cardiac cells of a human or other mammal. Alternatively, or additionally, each action potential can comprise one or more cells (e.g., a plurality of cells) of the bladder, brain, peripheral nerve, and / or other cell type of a human or other mammal. System 10 can be configured to perform contact mapping, non-contact mapping, or both. System 10 can include one or more catheters, catheter 100 shown, configured to be introduced into a cardiac chamber of the patient. Catheter 100 can include functional assembly 150 comprising at least one or more electrodes, electrode 155 shown. System 10 can include console 200 that is configured to operably attach to catheter 100, such as to record one or more signals from functional assembly 150, to deliver energy to functional assembly 150 (e.g., ablative energy), and / or to facilitate one or more other functions of system 10 as described herein.

[0089] Catheter 100 can comprise one or more catheters selected from the group consisting of: a mapping catheter; an ablation catheter; a delivery catheter, such as a right atrial access catheter; a catheter configured to be placed in the coronary sinus (e.g., a CS catheter); and combinations of these. One or more catheters 100 of system 10 can be configured to perform cardiac mapping and ablation, which can include creating a three-dimensional (3D) map of one or more chambers of the patient’s heart, and ablating cardiac tissue, such as tissue that is determined (e.g., by the clinician and / or automatically or semiautomatically by system 10) to be a contributing cause of an arrythmia of the patient.

[0096]

[0090] In some embodiments, console 200 includes navigation module 250 that is configured to provide one or more drive signals, and / or to record one or more signals, as described herein. Navigation module 250 can be configured to analyze the recorded signals to provide tracking (or “navigation” or “localization” herein) of at least a portion of one or more catheters 100 and / or other components of system 10 within the patient (e.g., to navigate functional assembly 150 within the cardiac chamber). Navigation module 250 can be configured to execute one, two, or more localization techniques, for example impedance-based localization, magnetic localization, and / or hybrid localization comprising both impedance-based and magnetic localization. Localization of one or more catheters or other devices that are inserted into the patient can be performed to determine the position and / or orientation (“position” herein) of at least a portion of the device (e.g., functional assembly 150 of catheter 100) during a clinical procedure. Navigation module 250 can include magnetic navigation module 251, impedance navigation module 255, or both, each configured to execute magnetic and impedance-based navigation processes, respectively, such as to determine spatial coordinates of one or more components of system 10 (e.g., electrodes 155, electrodes 40, or both) as described herein. In some embodiments, navigation module 250 includes conversion module 259 that is configured to integrate localization information determined by modules 251 and 255 to execute hybrid localization, as described herein. In some embodiments, catheter 100 includes one or more magnetic navigational sensors, coil 310 shown. Coil 310 can be located on a portion of functional assembly 150, shaft 110, and / or another portion of catheter 100. Coil 310 can include one or more magnetic coils and / or other magnetic field-responsive elements and can be configured to produce one or more signals related to a magnetic field, such as is described herein.

[0091] In some embodiments, console 200 includes treatment module 270 that provides one or more electric signals to be delivered to the patient via functional assembly 150, where the electric signals are delivered to treat the tissue. Console 200 can include diagnostic module 260 that records one or more signals (e.g., signals recorded via functional assembly 150) to diagnose the patient, for example to map the cardiac electrical pathways of the patient, as described herein. For example, system 10 can be configured to perform contact and / or non-contact mapping of cardiac electrical pathways. In some embodiments, non-contact mapping (e.g., where electrodes 155 of catheter 100 do not contact the cardiac walls while recording electrical activity) provides increased accuracy (e.g., versus contact mapping) for the mapping of cardiac electrical pathways, such as while the heart is in atrial fibrillation. For example, non-contact mapping can provide simultaneous global mapping of the majority (e.g., an entire) of a cardiac chamber (e.g., the electrical activity of an entire chamber can be mapped near-instantaneously). This simultaneous mapping of an entire chamber can provide increased accuracy when mapping complex, irregular cardiac electrical activity, for example when the heart is in atrial fibrillation.

[0097]

[0092] In some embodiments, console 200 includes anatomy module 280 that is configured to provide a digital anatomic model, for example a 3D model or other patient geometry data, such as a model of at least a portion of the patient’s heart, such as a chamber of the heart to be mapped by system 10, as described herein. Anatomy module 280 can be configured to import a 3D model, such as a 3D model generated from an imaging device, such as an MRI and / or a CT imaging device. Alternatively, or additionally, anatomy module 280 can be configured to provide signals and / or collect data from one or more devices of system 10 (e.g., catheter 100), such as to generate a 3D anatomic model. For example, catheter 100 can comprise one or more ultrasonic transducers configured to transmit and receive ultrasonic signals, and anatomy module 280 can be configured to generate a 3D model of the anatomy based on the ultrasonic data. In some embodiments, system 10 is configured to localize (i.e., determine the spatial coordinates of) one or more devices relative to the anatomic model (e.g., when the anatomic model is similarly localized to a 3D coordinate system established by system 10, as described herein). One or more localized devices can be displayed relative to the anatomic model, such as on a display of system 10, as described herein.

[0093] System 10 of Fig. 1 can include similar components and can otherwise be of similar construction and arrangement to system 10 described in reference to Fig. 1 A and / or other figures described herein.

[0098]

[0094] System 10 can include one or more functional elements, such as functional element 99 shown. One or more components of system 10, such as catheter 100 and / or console 200 can each include a functional element 99, such as when functional elements 199 and / or 299, respectively, each shown, comprise a functional element 99. Singly or collectively, various functional elements described herein can individually or collectively be referred to as “functional element 99”.

[0099]

[0095] In some embodiments, system 10 is configured to perform hybrid navigation, which can include establishing an impedance conversion matrix, calibrating the impedance conversion matrix, and using the impedance conversion matrix to localize one or more devices without magnetic sensors relative to the magnetic localization field and / or a 3D coordinate system established by navigation module 250. Impedance-based localization information, magneticbased localization information, and / or other localization information related to one or more grid cells of a 3D coordinate system (e.g., a voxel grid), can be stored in a dictionary type data structure (e.g., when stored in memory 52 of processing unit 50). In some embodiments, system 10 is configured to estimate electrode locations based on an impedance conversion matrix (e.g., instructions 53 stored in memory 52 of processor 51 are adapted to estimate the electrode locations). For example, system 10 can comprise a “z-loc” algorithm (e.g., algorithm 55 comprises a z-loc algorithm) that is configured to estimate the position of one or more electrodes (e.g., electrodes 155, electrodes 40, and / or other electrode) relative to the 3D coordinate system established by navigation module 250, based on impedance-based localization data.

[0100] Additionally, or alternatively, system 10 can be configured to estimate electrode locations with a hybrid algorithm (e.g., an algorithm 55 comprising a hybrid algorithm). For example, system 10 can comprise an “h-loc” algorithm that is configured to estimate the position of one or more electrodes relative to the 3D coordinate system established by navigation module 250, based on impedance-based localization data, magnetic-based localization data, and / or known catheter configurations. In some embodiments, system 10 is configured to obtain an optimal twisting angle in a local coordinate system. In some embodiments, system 10 is configured to compensate for respiration and / or cardiac motion. System 10 can comprise various methods and algorithms similar to the methods and algorithms described in applicant’s co-pending International PCT Patent Application Serial Number PCT / US2024 / 030585 (Docket No. ENC- 001-PCT-Parent), titled “Mapping and Navigation System”, filed May 22, 2024.

[0101]

[0096] Referring additionally to Fig. 1 A, a block diagram of another embodiment of a diagnostic mapping system is illustrated, consistent with the present inventive concepts. In some embodiments, one or more components of system 10 of Fig. 1 A are of similar construction and arrangement to the similar components described in reference to Fig. 1 herein.

[0102]

[0097] System 10 can include one or more data processing modules, processing unit 50 shown, that can be configured to perform and / or facilitate one or more of the functions of system 10 described herein. For example, processing unit 50 can perform and / or facilitate one or more processes, data collections, data analyses, data transfers, signal processing functions, energy deliveries, monitoring of one or more patient parameters, and / or other functions of system 10 (“functions of system 10” or “system functions” herein). Processing unit 50 can comprise one or more electronic elements, electronic assemblies, and / or other electronic components, such as components selected from the group consisting of: microprocessors; microcontrollers; state machines; memory storage components; analog-to-digital converters; rectification circuitry; amplifiers, filters, and / or other signal conditioners; sensor interface circuitry; transducer interface circuitry; and combinations of one, two, or more of these. For example, processing unit 50 can include at least one processor, processor 51 shown. Processor 51 can comprise a Von Neumann digital processor, a non-transitory computer, and the like. Processing unit 50 can comprise a signal processor, such as a signal processor operatively coupled between one or more electrodes (e.g., electrodes 155, electrodes 40, or both), and processor 51. Processing unit 50 can comprise a non-transitory computer readable medium and / or other forms of electronic data storage, memory 52 shown. Memory 52 can be coupled to processor 51, and memory 52 can store one or more sets of computer instructions, instructions 53 shown. Instructions 53 can comprise instructions used by processor 51 to perform one or more algorithms of system 10. For example, system 10 can comprise one or more algorithms, algorithm 55 shown, that are performed by processor 51. Additionally, or alternatively, instructions 53 can comprise instructions for running one or more applications of system 10, for example application 56 shown. Processing unit 50 can be configured to “run” application 56, such that application 56 can initiate, modify, stop, and / or coordinate the performance of various functions of console 200 and / or of system 10. In some embodiments, application 56 is configured to receive input from a user of system 10 (e.g., a clinician, nurse, or other operator of system 10), for example via a user interface (e.g., user interface 60 described herein). In some embodiments, algorithm 55 can comprise one or more machine learning, neural net, and / or other artificial intelligence algorithms (“Al algorithm” herein). All or a portion of one or more processing units 50 can be integrated into one, two, or more of the various components of system 10, such as console 200, a server (e.g., server 80 described herein), and / or other components of system 10.

[0103]

[0098] System 10 can include one or more user interfaces, user interface 60 shown. User interface 60 can provide and / or receive information to and / or from a user of the system (e.g., a clinician and / or other user of system 10). User interface 60 can include one or more user input components and / or output components. For example, user interface 60 can comprise a keyboard, mouse, touchscreen, and / or other human interface or other input component (e.g., as described herein), user input device 61. In some embodiments, user interface 60 can comprise a speaker, indicator light, haptic transducer and / or other human interface or other output component (e.g., as described herein), user output device 62. In some embodiments, user output device 62 comprises a video output component, such as display 63 shown. Display 63 can comprise a touchscreen display, for example when user input device 61 and user output device 62 collectively comprise display 63. In some embodiments, processing unit 50 is configured to provide an interactive graphical interface, GUI 65, such as a graphical user interface provided by application 56. GUI 65 can be displayed (e.g., displayed to a user of system 10) via display 63. In some embodiments, user interface 60 and / or GUI 65 comprise a virtual reality and / or augmented reality interface. One or more components of system 10 can comprise one or more portions of a user interface 60, such as catheter 100, console 200, and / or other components of system 10 described herein.

[0104]

[0099] System 10 can include one or more communication modules, communication module 70 shown. One or more devices of system 10 can comprise one or more portions of a communication module 70, such as catheter 100, console 200, and / or other components of system 10 described herein. Communication module 70 can be configured to provide communication (e.g., transfer commands, delivery information, patient information, and / or other data) between two or more components of system 10, such as via wired and / or wireless communication. For example, communication module 70 can include one or more transmitters and / or receivers, transceiver 71 shown. Transceiver 71 can comprise a wireless transceiver, such as a Bluetooth transceiver, a Near Field Communication (NFC) transceiver, a Wi-Fi transceiver, a cellular transceiver, a satellite-connected transceiver, and / or other short-range and / or long-range wireless transceiver. A wireless connection can include a short-range wireless connection, such as an NFC connection and / or a Bluetooth low energy (BLE) connection. In some embodiments, communication module 70 is configured to transfer data via an acoustic signal, such as an acoustic signal that is outside of the auditory range of the user. In some embodiments, communication module 70 is configured to communicate via one or more wired and / or wireless networks, such as network 75 shown. Network 75 can include a wireless network, such as a cellular network, LAN, WAN, VPN, the Internet, and / or other wireless network connecting two or more devices. In some embodiments, network 75 comprises a wired network, and / or a network including wired and wireless devices.

[0105]

[0100] Communication module 70 can be configured to transfer data between at least a first component of system 10 and at least a second component of system 10, as described herein. In some embodiments, the first component of system 10 comprises catheter 100. The second component can comprise another component of system 10, for example console 200.

[0106]

[0101] In some embodiments, system 10 includes one or more servers, server 80 shown, that can be configured to provide data storage and / or data processing for the providers of system 10 (e.g., the manufacturer and / or distributor of system 10) and / or the users or patients of system 10. As used herein, data processing can refer to the receiving of data, processing of data, transmission of data (e.g., transmitting the results of data processing), and / or the storage of data. Server 80 can comprise one or more processing units 50. Additionally, or alternatively, server 80 can include one or more data storage units for storing data collected by system 10, data 85 shown. In some embodiments, server 80 is configured to process data from various users of system 10, for example when the provider of system 10 maintains one or more servers 80 configured to process data for each (and / or a subset) of the users of system 10 (e.g., each of the clinicians, patients, and / or other users of system 10). Server 80 can comprise an “off-site” server (e.g., remotely located from the users of system 10), such as a server owned, maintained, and / or otherwise provided by the provider of system 10. Alternatively, or additionally, server 80 can comprise a cloud-based server.

[0102] In some embodiments, catheter 100 includes at least a portion of processing unit 50, at least a portion of user interface 60, and / or at least a portion of communication module 70, such as when catheter 100 comprises processing unit 105, user interface 106, and / or communication module 107, respectively, each shown. In some embodiments, console 200 includes at least a portion of processing unit 50, at least a portion of user interface 60, and / or at least a portion of communication module 70, such as when console 200 comprises processing unit 205, user interface 206, and / or communication module 207, respectively, each shown. In some embodiments, processing unit 205 is configured to perform one or more functions of navigation module 250, diagnostic module 260, treatment module 270, and / or anatomy module 280, such as are described herein. For example, processing unit 205 can be configured to process data received from catheter 100 by navigation module 250 and / or diagnostic module 260, such as to localize a device and / or to map cardiac electrical activity, as described herein. Algorithm 55 can be executed by processing unit 50 to perform one or more of the functions described in reference to the various modules of console 200. Console 200 can be configured to facilitate interaction between the clinician and system 10, for example providing an interface for procedure planning, execution, and / or review. Display 63 of user interface 60 can be coupled to console 200 and provide a visual output (e.g., GUI 65) for displaying real-time data, imaging, and / or other information needed by the physician during the procedure. In some embodiments, console 200 comprises two or more separate console units (e.g., two or more units each comprising a housing surrounding various components described herein). For example, console 200 can comprise a workstation, such as a workstation comprising a user interface, such as user interface 206, and a separate console (e.g., a separate unit operably attached to the workstation unit) housing one or more modules, such as navigation module 250, diagnostic module 260, treatment module 270, and / or anatomy module 280. In some embodiments, a workstation unit of console 200 comprises a user device such as a tablet or desktop computer that provides an interface for controlling a separate unit of console 200, such as a separate unit comprising signal and / or power generators and / or various data acquisition modules (e.g., components of modules 250, 260, 270, and / or 280, described herein). In some embodiments, two or more separate units of console 200 and / or two or more other components of system 10 (e.g., console 200 and catheter 100) are connected via one or more cables, such as cable 121 described in reference to Fig. 2 and otherwise herein.

[0103] Catheter 100 can include an elongated body, shaft 110 shown, extending from a user control portion, handle 120 shown. Functional assembly 150 can be located on a distal portion of shaft 110, for example when functional assembly 150 comprises an expandable array that is located at the distal end of shaft 110. An embodiment of functional assembly 150 comprising an expandable array is described in reference to Fig. 2 and otherwise herein.

[0107]

[0104] Functional assembly 150 can include an expandable array, such as an expandable array of one or more flexible struts, splines 151 shown, such as two, four, six, eight, ten, or twelve splines 151. Functional assembly 150 can include one or more flexible circuit portions, flex circuit 152 shown, such as a flex circuit 152 located on each side (e.g., the “inside” of each spline, toward the center of functional assembly 150, and the “outside” of each spline, away from the center of functional assembly 150) of each spline 151. Each flex circuit 152 can include one or more electrodes 155, where an electrode 155 positioned on an inside flex circuit 152 is oriented toward the center of functional assembly 150, and an electrode 155 positioned on an outside flex circuit 152 is oriented away from the center of functional assembly 150, for example as described in reference to Fig. 3 and otherwise herein.

[0108]

[0105] Functional assembly 150 can comprise a plurality of electrodes, such as multiple electrodes comprising a high density of electrodes 155, a high number of electrodes 155, or both. For example, functional assembly 150 can comprise at least four splines 151, such as at least six, eight, ten, or twelve splines 151. Each spline 151 can include at least three electrodes 155 per side (e.g., inward-facing and outward-facing, as described herein), such as at least six, eight, ten, twelve, fourteen, or sixteen electrodes 155 per side.

[0109]

[0106] Splines 151 can comprise a material selected from the group consisting of: nickel- titanium alloy; stainless steel; polyethylenimine (PEI); polyimide; and combinations of these. Each spline 151 can comprise a flexible and / or elastic member, such as an elastic ribbon (e.g., a flat sheet), such as a nickel-titanium (e.g., Nitinol) ribbon. Each spline can comprise a length of at least 15mm, and / or a length of no more than 35mm. Each flex circuit 152 can be operably attached to a portion (e.g., side) of an associated spline 151. For example, flex circuits 152 can be laminated, bonded, and / or otherwise attached to splines 151. Electrodes 155 can comprise a material selected from the group consisting of: gold; platinum; platinum-iridium; iridium oxide; PEDOT conductive polymer; titanium nitride; graphene; a precious metal alloy; and combinations of these. In some embodiments, each electrode 155 comprises a coating, such as a coating selected from the group consisting of: a gold coating; a coating configured to decrease the input impedance of the electrode; a PEDOT coating; an iridium oxide coating; a titanium nitride coating; an oxide coating; and combinations of these. Each electrode 155 can comprise a thickness of at least 0.01 pm and / or no more than 10pm. Each electrode 155 can comprise a surface area of at least 0.3mm2and / or no more than 5.0mm2.

[0110]

[0107] Each electrode 155 of functional assembly 150 can be operably attached to a portion of a flex circuit 152, for example to an electrical trace of flex circuit 152 that is operably (e.g., electrically) connectable to console 200, such via one or more electrical conductors (e.g., one or more wires or flex circuits), and one or more connectors configured to operably atach catheter 100 to console 200, such as cable 121 including connector 122 as described in reference to Fig. 2 and otherwise herein. In some embodiments, flex circuit 152 includes one or more vias connecting one or more electrical components on various layers of the circuit. In some embodiments, one or more vias connecting electrodes 155 to electrical traces of flex circuit 152 can comprise a coating, such as a gold or other coating.

[0111]

[0108] As described herein, catheter 100 can include one or more magnetic navigational sensors, such as coil 310, shown. Coil 310 can be located on a portion of functional assembly 150, such as to provide a signal related to the location, orientation, and / or geometric configuration (e.g., whether in an expanded or collapsed geometric configuration) of functional assembly 150, as described herein. Coil 310 can comprise a multi-degree of freedom sensor, such as a three, four, five, and / or six degree-of-freedom (DOF) sensor.

[0112]

[0109] Console 200 can include power supply 210 that provides electrical power to the various components of console 200. In some embodiments, power supply 210 is configured to provide patient isolation, for example when console 200 is configured to receive electrical power from an outlet or other external power source, and power supply 210 includes patient protection circuitry configured to protect the patient from the external power source. This isolation can protect the patient from potential electrical hazards, ensuring that catheter 100 can safely operate within the patient’s body.

[0113]

[0110] Diagnostic module 260 can include a cardiac signals processing assembly, EGM assembly 261. EGM assembly 261 can be configured to receive and record signals from electrodes 155 of catheter 100, and to process the recorded signals to diagnose and / or otherwise evaluate the patient, such as by mapping the cardiac electrical pathways of the patient.

[0111] Treatment module 270 can be configured io provide electrical energy to catheter 100 to be delivered to the tissue of the patient (e.g., via one or more electrodes 155), such as to ablate and / or otherwise treat the tissue. Treatment module 270 can include one or more signal generators, such as signal generator 271 shown, configured to generate the electrical signal to be delivered to the tissue. Signal generator 271 can be configured to generate an RF signal, such as a signal configured to thermally ablate tissue, and / or an electroporation signal, such as a signal configured to reversibly and / or irreversibly electroporate the tissue.

[0114]

[0112] Magnetic navigation module 251 can include a signal generator, magnetic signal generator 252, that generates one or more magnetic drive signals, and / or a signal receiver, magnetic signal receiver 253, that receives and records signals from one or more magnetic sensors, such as coil 310 of catheter 100. System 10 can include magnetic field generator 300 that receives the drive signal from magnetic signal generator 252 and generates one or more magnetic localization fields proximate the patient (e.g., to generate a magnetic field encompassing at least a cardiac chamber within which functional assembly 150 is to be inserted). Each coil 310 can generate a signal (e.g., a signal that is recorded by. magnetic signal receiver 253) related to the position of the. coil within the magnetic localization field generated by magnetic field generator 300. For example, each coil 310 can receive a magnetic signal (e.g., sense the magnetic field generated by magnetic field generator 300) and produce an electrical signal based on the received magnetic signal.

[0115]

[0113] Impedance navigation module 255 can include a signal generator, impedance signal generator 256, that generates one or more electric drive signals, and / or a signal receiver, impedance signal receiver 257, that receives and records signals from one or more electrodes, such as electrode 155 of functional assembly 150. System 10 can include one or more external patient electrodes, patch electrodes 40. System 10 can be configured to collect and process signals from an electrode 40 comprising a first plurality of electrodes positioned on respective skin regions of a patient, and an electrode 155 comprising a second plurality of electrodes positioned within the body of the patient. Impedance signal generator 256 can be configured to deliver the generated electric drive signals between sets of two or more patch electrodes 40, such as to establish a multi-axis impedance localization field within the patient. In some embodiments, a multi-axis impedance localization field can be configured as described in reference to Fig. 5A and / or Fig. 5B herein. In some embodiments, signals provided by impedance signal generator 256 comprise different frequencies, for example when signals comprising different frequencies are delivered between different pairs of patch electrodes 40, such that each axis of the multi-axis impedance localization field comprises a signal (e.g., current flowing through the patient between the patch pairs) with a different frequency.

[0116]

[0114] In some embodiments, navigation module 250 defines a 3D coordinate system surrounding the patient within which the various devices of system 10 can be localized. The magnetic localization field generated by magnetic field generator 300 can be correlated to the 3D coordinate system, such that rhe position of a magnetic sensor that is determined relative to the magnetic localization field via magnetic localization can be correlated to a position within the 3D coordinate system. Additionally, or alternatively, the multi-axis impedance localization field generated by signals delivered between patch electrodes 40 can be correlated to the 3D coordinate system, such that the position of an electrode that is determined relative to the impedance localization field via impedance-based localization can be correlated to a position within the 3D coordinate system. In some embodiments, a first conversion matrix (“magnetic conversion matrix” herein) can be used by conversion module 259 of navigation module 250 to convert position data determined by magnetic localization to position data relative to the 3D coordinate system. Additionally, or alternatively, a second conversion matrix (“impedance conversion matrix” herein) can be used by conversion module 259 of navigation module 250 to convert position data determined by impedance-based localization to position data relative to the 3D coordinate system, as described herein.

[0117]

[0115] As described herein, at least a portion of catheter 100, such as functional assembly 150, comprising one or more, coils 310 and / or electrodes 155, can be inserted into the patient, and navigation module 250 can be configured to localize the inserted portion of catheter 100 within the patient. Navigation module 250 can establish a 3D coordinate system for localizing catheter 100 within the patient. In some embodiments, magnetic signal receiver 253 is configured to record one or more signals from the one or more coils 310 of catheter 100, where the signals are related to the position of the coils 310 within the magnetic field generated by magnetic field generator 300. Conversion module 259 can be configured to localize coils 310 within the 3D coordinate system based on the signals recorded by magnetic signal receiver 253 (e.g., by establishing the magnetic conversion matrix, as described herein). Impedance signal receiver 257 can be configured to record one or more signals from one or more electrodes 155 of catheter 100, where the signals are related to the position of the electrodes 155 within an electrical field generated by signals provided by impedance signal generator 256 to patch electrodes 40, as described herein. In some embodiments, signals recorded by impedance signal receiver 257 comprises phase values, magnitude values, and / or both, that are related to the multiaxis impedance field described herein. In some embodiments, patch electrode 40 includes one or more magnetic sensors, for example coil 45 shown, such as a sensor that is configured to produce a signal related to the location of patch electrode 40 within the 3D coordinate system based on magnetic localization signals, such that patch electrode 40 can be localized to the 3D coordinate system, as described herein.

[0118]

[0116] One or more coils 310 and electrodes 155 of catheter 100 can form fiducial pairs, where the physical relationship between the elements of the fiducial pairs have a known physical spatial relationship. Conversion module 259 can be configured to establish the impedance conversion matrix based on the known relationship of the fiducial pairs, the localization data of the coils 310 of the fiducial pairs, and the signals recorded by impedance signal receiver 257 from the electrodes 155 of the fiducial pairs. In some embodiments, impedance signal receiver 257 is configured to record signals from one or more electrodes 155 not fiducially paired with a coil 310 (e.g., unpaired electrodes 155 of a catheter including one or more fiducial pairs, and / or electrodes 155 of another catheter 155 that does not comprise any coils 310). Conversion module 259 can be configured to localize one or more electrodes 155 within the 3D coordinate system based on the signals recorded by impedance signal receiver 257 and the impedance conversion matrix.

[0119]

[0117] In some embodiments, conversion module 259 is configured to calibrate the magnetic conversion matrix and / or the impedance conversion matrix (singly or collectively “conversion matrices” herein). Conversion module 259 can be configured to calibrate a conversion matrix based on fitting the localized position of one or more elements (e.g., coils 310 and / or electrodes 155) to a known physical spatial relationship of the elements of catheter 100 (e.g., based on a known model of catheter 100).

[0120]

[0118] In some embodiments, one or more magnetic sensors (e.g., coils 45) can be attached to the patient (e.g., positioned on the skin of the patient), and signals from these sensors can be used by system 10 to compensate for patient body motion during a procedure, such as motion relative to magnetic field generator 300. For example, two or more magnetic sensors (e.g., patch electrodes 40 comprising coils 45) can be attached to the patient. These sensors can be positioned at the same location as patch electrodes 40 (e.g., coils 45 that are integral to patch electrodes 40), and / or can be positioned at other locations on the body that are separate from patch electrodes 40 (e.g., non-electrode patient patches comprising coil 45). Signals recorded from coils 45 can be used to track the motion of the torso of the patient relative to the 3D coordinate system and can provide information to an algorithm (e.g., algorithm 55) that compensates for undesired, artifactual components of motion that are imposed upon navigation of one or more catheters within the body. The location and / or orientation of coils 45 can be recorded at the start of the procedure for reference. During the procedure, the current location and / or orientation of coils 45 can be used to construct a mathematical transformation. The transformation can be linear or non-linear, and its inverse transformation can be used to remove components of body motion from the magnetic-based and impedance-based catheter localization information. This method of body motion compensation can be applied on navigation of one or more catheters or treatment or diagnostic devices of system 10 that are localized within the body. The linear transformation can be any of “identity” (no motion), “translation” (movement in space without rotation), “rotation” (change of orientation in space), “scale” (change of volume), “shear” (sliding and stretching motion along one direction), or any combination of these. In some embodiments, the linear transformation simply amounts to a rigid body motion (a combination of a “translation” and a “rotation”). More accurate nonlinear transformations can also be constructed when three or more coils 45 are used. In some embodiments, compensation for respiratory motion can be performed using the “scale” transformation type. Linear affine transformation for different motion types is provided by the following equations.

[0121]

[0122]

[0119] Referring now to Fig.2, a side view of an embodiment of a catheter including a handle and a functional assembly is illustrated, consistent with the present inventive concepts. Catheter 100 and / or other components of system 10 described in Fig. 2 can be of similar construction and arrangement as the similar components described in reference to Fig. 1 and otherwise herein. Catheter 100 can include a user control portion, handle 120. Shaft 110 can extend distally from handle 120, with functional assembly 150 positioned proximate a distal portion, distal portion 118 shown, of shaft 110. Catheter 100 can include one or more interconnects, cable 121, including one or more conduits, such as one or more electrical, fluid carrying, optical, mechanical linkages, and / or other conduits configured to operably attach catheter 100 to console 200 and / or other components of system 10. Cable 121 can include connector 122 that removably attaches to a component of system 10 (e.g., console 200), and creates one or more connections, such as one or more electrical, fluid, optical, mechanical, and / or other operable connections between catheter 100 and the connected component. In some embodiments, cable 121 provides a fluid connection between console 200 and catheter 100, for example when catheter 100 is configured to provide irrigation via one or more lumens extending through shaft 110 to one or more irrigation ports proximate functional assembly 150, not shown but known to those skilled in the art.

[0123]

[0120] Handle 120 can include one or more user controls (e.g., one or more controls of user interface 60, such as user input device 61). For example, handle 120 can include one or more mechanical controls that allow the user to mechanically manipulate a portion of catheter 100, such as steering control 125a and / or deployment control 125b, each shown. Steering control 125a can operably attach to one or more steering cables (not shown) that are arranged to manipulate the articulation of the distal portion 118 of shaft 110. Deployment control 125b can operably attach to one or more linkages (not shown but described herein) that are arranged to manipulate the geometry of functional assembly 150, for example to transition functional assembly 150 from a linear (compacted) geometry, to a radially expanded geometry (e.g., when functional assembly 150 comprises an expandable basket arrangement, as described herein). Additionally, or alternatively, handle 120 can include one or more user input controls (e.g., user inputs configured to provide an input signal to console 200), user input 126 shown. User input 126 can be configured to provide an input signal, such as a signal configured to start and / or stop a process of system 10 described herein, for example to record data (e.g., during a cardiac mapping process) and / or to deliver energy (e.g., during an ablation process). Handle 120 can include one or more outputs (e.g., one or more outputs of user interface 60, such as user output device 62). For example, handle 120 can include output 127, such as an output device comprising a visual indicator, audible indicator, haptic indicator, and / or other output device, such as described herein.

[0124]

[0121] Referring now to Fig. 3, a perspective view of the distal portion of an embodiment of a catheter including a basket-like functional assembly is illustrated, consistent with the present inventive concepts. Catheter 100 and / or other components of system 10 described in Fig. 3 can be of similar construction and arrangement as the similar components described in reference to Fig. 1 and otherwise herein. In the embodiment of Fig. 3, functional assembly 150 comprises a basket-like array, shown in an expanded geometry. Fig 3 shows the distal portion of catheter 100, including distal portion 118 of shaft 110, and functional assembly 150. Shaft 110 terminates at distal end 119, and can include one or more lumens extending therethrough, such as lumen 115 extending proximally from distal end 119 through shaft 110. Distal portion 118 of shaft 110 can include a coupling mechanism, coupler housing 114, that connects functional assembly 150 to shaft 110, as described herein. Catheter 100 can include control assembly 160 that is constructed and arranged to control the geometry of functional assembly 150. Control assembly 160 can include one or more linkages, such as puller tube 161 shown, and a distal hub assembly, housing 162, that attaches to and / or forms the distal portion of functional assembly 150. In some embodiments, for example as shown in Fig. 3, the proximal portion of each spline 151 is fixedly attached to coupler housing 114, and the distal portion of each spline 151 is fixedly attached to housing 162. Puller tube 161 can be advanced and / or retracted through lumen 115, such as to adjust the distance between housing 162 and distal end 119 of shaft 110, thereby adjusting the geometry of functional assembly 150 (e.g., by straightening and / or deflecting each spline 151 to transition between a linear geometry and an expanded geometry). Puller tube 161 can be operably attached to a user control, such as deployment control 125b described in reference to Fig. 2 herein. Alternatively, or additionally, puller tube 161 can be operably attached to a linear actuator or other electromechanical actuator, such as when catheter 100 is configured to be automatically and / or semi-automatically controlled (e.g., robotically controlled). Functional assembly 150 is shown in an expanded geometry in Fig. 3. Fig. 4, described herein, shows functional assembly 150 in a linear geometry. Functional assembly 150 can be configured to expand to a diameter of up to at least 12mm, such as at least 16mm and / or up to no more than 35mm, such as no more than 24mm.

[0125]

[0122] Functional assembly 150 can comprise distal surface 159, as shown. In some embodiments, distal surface 159 comprises the distal most end of catheter 100, for example when no part of shaft 110, puller tube 161, and / or housing 162 extends beyond distal surface 159 (e.g., catheter 100 comprises a “nose-less” catheter). For example, the distal ends of splines 151 can be contiguous with distal surface 159, as shown.

[0126]

[0123] Catheter 100 can include one or more coils 310 configured to enable magnetic localization of functional assembly 150 and / or other portions of catheter 100, as described herein. In some embodiments, catheter 100 includes at least a first coil 310a located proximate coupler housing 114 (e.g., at a fixed location relative to distal end 119 of shaft 110), and a second coil 310b located on or within housing 162, each shown. System 10 can be configured to localize each of coils 310a,b and to determine the deployment status of functional assembly 150 based on the determined distance between the coils.

[0127]

[0124] Each spline 151 can include (e.g., positioned thereon) a set of one or more “outwardfacing” electrodes (electrodes facing away from the center of functional assembly 150), electrodes 155a, and / or a set of one or more “inward-facing” electrodes (electrodes facing toward the center of functional assembly 150), electrodes 155b, each shown. Each electrode 155 can be electrically coupled to one or more conduits, such as one or more traces of a circuit assembly, such as flex circuit 152 described herein. In some embodiments, flex circuit 152 comprises a flexible circuit board construction, such as flexible substrate with electrical traces connecting various components of the circuit (e.g., electrodes 155 located thereon).

[0128] Alternatively, or additionally, flex circuit 152 can include one or more wires that electrically connect to various electrical components of functional assembly 150 (and / or catheter 100), such as individual wires without a “circuit board” like substrate. Functional assembly 150 can comprise one or more discrete flex circuits, where each flex circuit 152 can comprise all or a portion of a discrete flex circuit, for example when a single flex circuit comprise two or more portions, each of which are configured to be positioned relative to a portion of functional assembly 150. Various discrete flex circuits can be interconnected by one or more connectors, wires, or other electrical conduits.

[0129]

[0125] Each spline 151 can include (e.g., positioned thereon) a flex circuit 152a positioned on the outside of the spline, and / or a flex circuit 152b positioned on the inside of the spline (e.g., such that each outward-facing electrode 155a is positioned on a flex circuit 152a, and each inward-facing electrode 155b is positioned on a flex circuit .152b, as shown). In some embodiments, each flex circuit 152a and 152b of each spline 151 comprises a single discrete flex circuit that is “folded” such that a first portion of the flex circuit comprises the outward flex circuit 152a, and a second portion of the flex circuit comprises the inward flex circuit 152b. Alternatively, or additionally, each of the flex circuits 152a,b of each spline 151 can comprise discrete flex circuits, such as discrete flex circuits that are interconnected as described herein. In some embodiments, functional assembly 150 comprises a first discrete flex circuit comprising each outward flex circuit 152a (e.g., a single discrete flex circuit comprising multiple elongate portions that are each positioned along the outside of an associated spline 151), and / or a second discrete flex circuit comprising each inward flex circuit 152b (e.g., a single discrete flex circuit comprising multiple elongate portions that are each positioned along the inside of an associated spline 151). In some embodiments, a single discrete flex circuit comprises multiple elongate portions each comprising a flex circuit 152a or 152b, where the single flex circuit is configured to be folded and / or otherwise manipulated (e.g., in a manufacturing process), to align with the respective inside and / or outside of splines 151.

[0130]

[0126] Referring now to Fig.4, a side view of the distal portion of an embodiment of a catheter including a basket-like functional assembly is illustrated, consistent with the present inventive concepts. Catheter 100 and / or other components of system 10 described in Fig. 4 can be of similar construction and arrangement as the similar components described in reference to Fig. 1 and otherwise herein. In the embodiment of Fig. 4, functional assembly 150 comprises a basket-like array, shown in a collapsed (“linear”) geometry. Fig. 4 shows functional assembly 150 extending from distal end 119 of shaft 110. Distal portion 118 of shaft 110 includes coupler housing 114, as described herein. Puller tube 161 is shown in an extended position (extended distally from shaft 110), such that housing 162 of control assembly 160 is positioned away from coupler housing 114, extending splines 151 into the linear geometry shown. Coils 310a,b are shown located within coupler housing 114 and housing 162, as described herein. In the geometry shown, the distance between coils 310a,b is greater than the relative distance between the coils in the expanded geometry of functional assembly 150 shown in Fig. 3. Each spline 151 can include flex circuits 152 (outward flex circuit 152a shown), and / or electrodes 155 (outwardfacing electrodes 155a shown). Distal surface 159 of functional assembly 150 comprises the distal most portion of catheter 100, as shown and described herein.

[0131]

[0127] Referring additionally to Fig. 4A, a cross-sectional view of the functional assembly of Fig. 3 is illustrated, consistent with the present inventive concepts. Coil 310a is shown positioned within coupler housing 114. Coil 310a can comprise a hollow structure, as shown, such that puller tube 161 can slidingly extend through coil 310a. Coil 310b is shown positioned within housing 162. The distal end of each spline 151 can be fixedly attached to the distal end of housing 162, forming distal surface 159, as shown. The proximal end of each spline 151 can extend into and be fixedly attached within coupler housing 114, as shown.

[0132]

[0128] Referring now to Figs. 5A and 5B, anatomic views showing embodiments of patch electrodes placement arrangements are illustrated, consistent with the present inventive concepts. Patch electrodes 40 and / or other components of system 10 described in Figs. 5 A and 5B can be of similar construction and arrangement as the similar components described in reference to Fig.

[0133] 1 and otherwise herein. System 10 can include one or more sets (e.g. “pairs”) of two or more patch electrodes 40, such as a first pair, electrodes 41a,b, a second pair, 42a, b, and / or a third pair 43a,b, as shown in Figs. 5A and 5B. Impedance signal generator 256 of impedance navigation module 255, not shown but described herein, can be configured to provide an electrical signal between each electrode of a pair of patch electrodes 40, such as to generate an electrical impedance field between the electrodes. Signals comprising varying electrical properties (e.g., signal frequencies) can be provided between different pairs of patch electrodes 40, such as to create a multi-axis impedance localization field. Impedance navigation module 255 can receive and process signals from one or more electrodes located on a patient inserted device (e.g., electrodes 155 of catheter 100), where the signals are related to the multi-axis impedance localization field and are processed to localize the patient inserted device.

[0134]

[0129] The placement and alignment of each pair of patch electrodes 40 can be configured based on procedural needs and / or the patient’s physique (e.g., the patient’s body size and shape). Figs. 5A and 5B show two non-limiting embodiments of patch electrode 40 placement configurations. Fig. 5A shows the pair of patient patch electrodes 41a,b positioned centrally on the upper chest and lower back, respectively, of the patient, defining a first axis of the impedance electrical field. The pair of patch electrodes 42a, b are shown positioned on the lower right of the front of the torso and upper left of the back, respectively, of the patient, defining a second axis of the impedance electrical field. The pair of electrodes 43 a, b are shown positioned on the lower left of the front of the torso and the upper right of the back, respectively, of the patient, defining a third axis of the impedance electrical field. Fig. 5B shows the pair of patch electrodes 41a,b similarly positioned centrally on the upper chest and lower back, respectively, of the patient, defining a first axis of the impedance electrical field. The pair of patch electrodes 42a, b are shown positioned centrally on the lower torso and upper back, respectively, of the patient, defining a second axis of the impedance electrical field. The pair of patch electrodes 43 a, b, are shown positioned on the right and left sides of the torso, respectively, of the patient, defining a third axis of the impedance electrical field. In some embodiments, patch electrodes 40 are positioned, and / or the signals provided are configured, such that the physical locations of zero amplitude (e.g., the null points) of the composite impedance electrical field are located proximate the heart of the patient, but outside of a region of interest (e.g., proximate but outside of a heart chamber), such as to avoid null points (e.g., locations where a the localization signal comprises zero amplitude) within the region of interest. Alternatively, or additionally, the physical location of zero-amplitude of the field for one or more axes can be configured away from the heart of the patient.

[0135]

[0130] Clinical cardiac mapping is an established practice in cardiac electrophysiology, which evolved from 2D recording of multiple intracardiac signals obtained from multiple catheters positioned within the chambers of the heart under the limited visual guidance of x-ray fluoroscopy. Multiple 2D signals enable physicians to predict and locate sites within the chamber that initiate and maintain specific types of cardiac arrhythmias. Such sites are commonly treated with radiofrequency ablation, which destroys the cardiac cells responsible for generating these arrhythmias and restores normal heart rhythm and function. The radiofrequency energy is delivered through specialized electrode catheters designed for this purpose. Additional types of ablative energy sources include cryothermy and high-amplitude, pulsed electric fields. The types of arrhythmias that can be effectively treated with 2D recording are limited, compared to the full range of arrhythmias that are prevalent and require treatment, especially complex and irregular arrhythmias such as atrial fibrillation (AF).

[0136]

[0131] Consequently, 2D recording evolved into 3D cardiac mapping, which enables physicians to visualize a 3D representation of multiple catheters displayed on a computer screen, as well as 2D signal traces obtained from the catheter electrodes. Commercial mapping systems that are used in clinical procedures provide software features that enable 3D construction and display of cardiac chamber anatomy. Catheters are maneuvered around the chamber to generate a 3D “point-cloud” of location coordinates that demarcate the volume within the chamber, and, ultimately, the physical boundary of the endocardial surface of the chamber. A triangular mesh that optimally encloses the point-cloud is formed to establish the endocardial surface of the chamber. Catheter signals sampled across the surface-mesh are processed and displayed upon the 3D cardiac anatomy as a color map of signal amplitude and timing of tissue activation. Ablation catheters are graphically visualized and navigated upon the surface-mesh to sites that are responsible for generation of arrythmia and are targeted for ablation treatment. A much broader range of clinically relevant types of arrhythmias can be assessed and treated with 3D mapping systems than with 2D recording systems.

[0137]

[0132] There are two general categories of 3D mapping methodology: 1) sequential; and 2) global. Sequential mapping is applied on regular, periodic arrhythmias in which the global pattern of activation can be “stitched” together from samples of signals obtained “point-by- point” at multiple locations across the chamber. Global mapping is applied on any arrhythmia, both regular and irregular, by taking simultaneous, instantaneous, “snapshots” of signals across the entire chamber. Each snapshot is taken in a sequence of global samples through time. Global mapping contains all spatiotemporal information, which enables mapping of regular, irregular, non-sustained, and single-beat arrhythmias over a broad range of complexity, including AF.

[0138]

[0133] The most common methodology in sequential mapping obtains signals from the heart tissue by direct contact with electrode catheters that are manipulated around the chamber, step- by-step.

[0139]

[0134] The most common methodology in global mapping is cardiac activation reconstruction from noncontact signals. Such signals can be obtained from an array of electrodes distributed across the body surface, within the chamber cavity, or both. Historically, noncontact reconstruction of cardiac activation began in a first-generation, in which the voltage-based signals were acquired from an array of multiple, evenly-distributed electrodes on an elliptically- shaped or ellipsoidal probe that was placed in the cavity of the chamber of interest. The noncontact, “cavitary” signals were inversely transformed to voltage-based signals upon the cardiac chamber anatomy displayed on the computer screen. Electric field theory was applied to accurately model the distribution of cardiac potentials within the heart and across the body torso. This methodology evolved to a higher-resolution second-generation, in which the acquired array of voltage-based signals is inversely transformed to charge-density-based signals upon the cardiac chamber anatomy displayed on the computer screen. Electric field theory was applied to accurately model the location of charge density within the myocardial tissue.

[0140]

[0135] Charge-density -based methodology is an evolution aimed at reconstructing the electric source of the signal, namely the double-layer of charge density that briefly emerges and disappears in the extracellular medium, which results from the action of ion channels within the cell membrane. Accordingly, the ideal, physiologically-based source for mapping cardiac conduction lies in the biophysical process that generates the double-layer of charge density, namely the cardiac action potential. To date, there are no clinical mapping systems that provide global mapping of cardiac action potentials.

[0141]

[0136] Cardiac mapping systems include apparatuses and features for localizing the position of electrodes or the catheter body or both. Electrode “patches” are placed on the body surface and low-magnitude currents are passed between pairs of patches to localize the position of electrodes using an electrical impedance-field. Electromagnetic coils are placed on the body surface and / or within the catheter shaft and a magnetic field is transmitted to the body from a fixed electromagnetic source to localize the position of the magnetic sensors using electromagnetic induction. A 3D coordinate system is established trough the localization systems to support navigation of catheters, construction of cardiac chamber anatomy, and guidance of ablation therapy to identified targets from maps of cardiac activation.

[0142]

[0137] Cardiac source modeling is a mathematical model that can be applied at the cellular level to accurately reconstruct the electric potential that can be measured inside or outside the heart. Electric charge is generally recognized as the source of cardiac potential. Source modeling can be utilized to understand irregular electrical activity on the atria, such as AF, through simulation and non-contact mapping. Non-contact mapping is a cardiac mapping approach that provides a global picture of electrical activation at any point upon a heart chamber. It can be non- invasive (e.g., body-surface ECGI™) or invasive (e.g., intracardiac AcQMap™). Invasive non- contact mapping transforms electric potentials measured within the chamber to the electric potential or charge-density sources located on the chamber surface. These measured potentials contain far-field information coming from all four chambers of the heart. Such far-field information presents an interference that can diminish the accuracy of reconstruction of potentials or charge-density in the atria, resulting jn incomplete mapping of an arrhythmia cycle- length, such as in atrial flutter. This far-field effect is less severe on the contact mapping approach, however, contact mapping cannot provide a global map of electrical activation during an irregular arrhythmia, thereby limiting its application in AF.

[0143]

[0138] System 10 can be configured to perform contact mapping, non-contact mapping, or both. In non-contact mapping, from the point of view of inverse reconstruction, the problem is underdetermined, as the number of measurements performed are usually lower than the number of segments / elements to be calculated on the cardiac surface. In addition, this problem needs to be solved for each sampled time-point, which requires computationally feasible regularization methods that can quickly find an accurate solution. System 10 can be configured to perform the following approach: (1) compute a linearized forward model (as forward matrix A, such that at any time-point, Ax ≈ y, where y is the measured potential, and x is the unknown potential on cardiac surface, and dim(x) » dim(y)), and (2) solve it as ridge regression (i.e. linear regression with L2 regularization: for each time point. Depending on the parameter, λ, the solution can be very smooth spatially, with temporal consistency. In some embodiments, system 10 can be configured to urovide solutions that rapidly derive accurate, and as well as spatially and temporally consistent morphologies of cardiac repolarization.

[0144]

[0139] Ultimately, system 10 uses the reconstructed signals to estimate the cardiac activation time across the entire heart-chamber of interest. Both complex and heuristic spatially and temporally constrained methods are used by system 10 to accurately estimate the activation time at each point on the cardiac surface. Since the action potential (AP) is being reconstructed, a highly accurate estimate of activation time from the fundamental principles of electrophysiology is achieved. In addition, a clinically relevant reconstruction of the action potential duration (APD) is achieved, as well as reconstruction of repolarization phases two and three of the action potential.

[0145]

[0140] The present inventive concepts include novel systems, devices, and methods to reconstruct cardiac sources from measured voltages within a cardiac chamber and / or upon the body surface. The inventive concepts are advancements from previous methods, such as those that apply (1) voltage as a source using Laplace’s Equation [1], and (2) charge as a source using Poisson’s Equation [2] to achieve higher resolution by reducing the intrinsic smoothness of voltage generated by spatial superposition.

[0146]

[0141] Cardiac source mapping performed by system 10 can reduce the scope of invasiveness and duration of electrophysiological procedures, as it instantaneously enables accurate identification of arrhythmogenic regions of the heart. The method can have applications in the diagnosis and treatment of a variety of heart conditions, including arrhythmias, heart failure, and congenital heart defects.

[0147]

[0142] Cardiac source mapping performed by system 10 can include the two steps depicted in Figs. 6 and 7: (1) forward modeling to establish the source and field relationship, also known as the “lead field”, which is derived from the inputs of the cardiac chamber anatomy and the spatial coordinates (also referred to as “spatial locations”) of electrodes; and (2) inverse solving to calculate the cardiac sources from voltages measured by the electrodes within the chamber and / or upon the body surface.

[0148]

[0143] In some embodiments, five or more forward models can be applied to derive the source- voltage relationship and / or their derivatives.

[0149] STAGE 1 - Forward Modeling

[0144] System 10 can perform forward modeling, in which the relationship between the cardiac source and the electric field generated by the sources is established. Since the relationship is governed by field theory, which asserts that the field generated by the source can be sensed at a distance, and does not require physical contact to the source, forward modeling can incorporate the cardiac-source information from all locations of the cardiac surface, irrespective of placements of electrodes 155 of catheter 100. In other words, system 10 can provide a global map of cardiac sources. In some embodiments, system 10 provides five (e.g., at least five) forward models based on different assumptions on cardiac sources. Although system 10 operates under the assumption that the voltages are measured from within the heart chamber, the same source-field relationship can be extended to voltage measurements acquired from the body surface (e.g., via patch electrodes 40) or combined from both within the heart chamber (e.g., via electrodes 155) and across the body surface (e.g., via patch electrodes 40).

[0150]

[0145] A general form of the forward problem used by system 10 can be written as: where Y represents the m × t time-series of measurements from electrodes (e.g., electrodes 155, patch electrodes 40, or both), with “m ” measurements and “t” time samples. S is the n × t cardiac sources, represented by “n ” action potentials and “t” time samples. A is the known lead field consisting of the linear relationship between the source and measurements. A can be derived by the integral on each polygonal face-element of the cardiac surface mesh, for example by applying the boundary element method (BEM), or it can be derived directly at each coordinate-point that lies upon the cardiac surface using a meshless method.

[0151] Approach 1: Poisson equation

[0152]

[0146] The change in concentration of various ions (Na+, K+, Ca2+) creates polarization that is associated with bound charges (ppol) and generates an electric field throughout the extracellular space. This electric field is defined by Poisson’s Equation [ref]:

[0153] (1) where S denotes the cardiac surface, tl is the measurement domain, V (r; t) is the measured potential at time t, ∈bis the permittivity of blood, and charge density and polarization are connected by

[0154]

[0147] Using the relationship between polarization and electric field and we have: where A is the Laplacian operator and Vmis the action potential, as measured across the cell membrane. Vmapplies here because polarization is coupled across the intracellular and extracellular space. Therefore, when the gradient of this electric field is calculated, the action potential results, as formally defined. Combining all the above:

[0155] (2)

[0156] Letting T1denote a transfer matrix and L denote a discretized Laplacian operator, the lead field matrix A can be derived as:

[0157] Approach 2: Green function

[0158]

[0148] Using a general form of Green’s theorem, an alternative approach to derive the action potential comes from another form of (2):

[0159] (3)

[0160] Letting T1denote a transfer matrix and G denote a gradient operator, the lead matrix A is represented as:

[0161] Given a catheter 100 with a sufficiently large number of electrodes 155, such that adjacent electrodes are sufficiently close (e.g., within 1mm, or 3mm, or 5mm, or 20mm of another electrode 155), the gradient of the voltage measurements from the catheter 100 can be accurately calculated by system 10. In some embodiments, adjacent electrodes 155 are spaced at least 1mm, or 3mm, or 5mm apart. The gradient calculation reduces or nullifies the electric fields that are similar, or “common” on adjacent electrodes 155 of the catheter 100. The ventricles are more distant from the chamber being mapped than the adjacent atrium, with respect to the catheter 100. Accordingly, the distance between adjacent electrodes 155 is smaller than the distance between the catheter 100 and the ventricles of the heart of the patient. With such smaller distances between electrodes 155, the far-field interference from the ventricles is reduced in the differentials between the adjacent electrodes 155, while the electrodes 155 still uniquely sense the electric field from the adjacent regions of the heart chamber being mapped. Therefore, this approach performed by system 10 has the capability to create regional maps of action potentials. These regional maps can reduce computational burden, as well as provide better accuracy.

[0149] Another form of forward problem can be derived from the gradient of voltage measurements:

[0162] Here, the n x t source matrix is the same as above, while denotes a 3m x t matrix comprised of the directional derivatives of Y with respect to x, y, and z .

[0163] The lead field matrix is then 3m × n, which can be derived by the following three approaches.

[0164] Approach 3: Gradient of Poisson equation

[0165]

[0150] Taking the gradient on both sides of equation (2) results in:

[0166] Rearranging terms results in:

[0167] After discretizing, what results is the matrix representation , where the source matrix 5 is the same as in Approach 1 and Approach 2 described hereabove, represents the derivative of measurements, and the 3m × n lead field matrix A contains the transfer matrix T1, the Laplacian operator L, and gradient operator G.

[0168] Alternatively, the gradient of the transfer matrix, denoted as U1, can be computed mathematically. In this approach, the 3m × n lead field matrix A contains the transfer matrix U1and the Laplacian operator L.

[0169] Approach 4: Gradient of Green function

[0170]

[0151] Alternatively, the gradient on the action potential formulation can be calculated (eq. (3)) and the above steps followed. Then, another linear system results where A does not contain the Laplacian operator but has the Divergence operator and unknowns are the action potentials. Mathematically, it is defined as:

[0171] After discretizing, what results is the matrix representation: , where the 3m × n lead field matrix A contains two gradient operators G and the transfer matrix Tz.

[0172] Alternatively, the gradient of the transfer matrix, denoted as Uz, can be computed mathematically. In this approach, the 3m X n lead field matrix^ contains the transfer matrix Vz and the gradient operator G.

[0173] Approach 5: Gradient of xx model

[0174]

[0152] The gradient-based approach can also be modeled as: where giis the conductivity of intercellular space, σ0is the conductivity of the medium, and integration is carried out over the cardiac surface.

[0175]

[0153] Now, calculating the gradient on both sides of the above equation,

[0176]

[0154] After discretizing, what results is the matrix representation: , where represents the derivative of measurements, and the 3m x n lead field matrix A contains the gradient operator G and transfer matrix T3.

[0177]

[0155] Alternatively, the gradient of the transfer matrix, denoted as U3, can be computed mathematically. In this approach, the 3m × n lead field matrix contains the transfer matrix U3.

[0178]

[0156] In the alternative gradient-based approaches 3, 4, and 5, the number of unknowns remains the same, while the number of voltage measurements has increased by three. This approach can reduce the under-determinedness of the system and thereby improve the condition- number of the “A” matrix. Additionally, obtaining the gradient of the voltage measurements reduces the measured far-field interference, and thereby enables generation of regional maps of action potentials. These regional maps can be generated with reduced computational burden, as well as improved accuracy.

[0179] STAGE 2 - A time series model of action potentials

[0180]

[0157] System 10 can be configured to utilize a time series model of action potentials in at least two different ways. For example, in one configuration, system 10 utilizes a time independent model in which each instance of time is treated separately. This approach is valid because of the quasistatic nature of the cardiac electric field. Alternatively, or additionally, in another configuration, system 10 utilizes a time dependent model in which a predefined, action potential morphology is fitted to achieve a physiologically accurate result. For example, one preferred parameterization of the action potential (e.g., cardiac action potential) is the product of three sigmoid functions: where α, β , γ are constants defining the steepness of the upstroke and downstroke, δ is the timing of local depolarization, ρ is the timing of local repolarization, and T is the translation parameter. Note that two exponential functions are used to define repolarization to highlight phases 2 and 3 of the action potential (e.g., cardiac action potential). This parameterization can handle multiple activations and morphological variations. Fig.8 illustrates an example in which multiple cardiac activations occur at a fixed but arbitrary location on the heart surface, at an arbitrary time point, and parameterized with the above function.

[0181]

[0158] Fig.9 illustrates that the action potential duration can be formulated with the equation immediately hereabove.

[0182]

[0159] As observed in Figs. 8 and 9, this parametric approach allows recovery of three temporal properties: (1) morphology or shape of the action potential, (2) temporal instance of action potential occurrence, and (3) action potential duration.

[0183]

[0160] The exponential decaying downstroke of the ground truth action potential shown in

[0184] Fig. 9 is prominent in the ventricle, but in the atrium, the ground truth action potential shape can have a different, more linearly decaying downstroke. In those cases, action potential shape can also be modeled as a piecewise-linear triangular shape, as shown in Fig. 10, and represented by: where 6 is the timing of local depolarization, p is the timing of local repolarization, and p is a small positive constant of depolarization duration. If this piecewise-linear shape function is used, the parameters, function and gradient evaluations would be different, but the rest of the procedures are the same.

[0185]

[0161] Another shape variation is the combined exponential-linear shape shown in Fig. 11, and represented by: where α, β , γ are constants defining the steepness of the upstroke and downstroke, δ is the timing of local depolarization, and ρ is the timing of local repolarization. Here, the upstroke is more exponential-like, and the downstroke is more linear-hke, as compared to the results shown in Fig. 10.

[0186]

[0162] In some embodiments, system 10 is configured to smooth the sharp comers due to linear components in each shape above, such as by utilizing the more “huberized” shape variations that are listed below. In these embodiments, the non-smooth sharp comer present in above piecewise-linear triangular shapes are huberized, meaning that these sharp comers are replaced by system 10 via a globally smooth function composed of linear and quadratic parts. Note that all huberized functions listed below are gradient Lipschitz continuous (i.e. continuous and differentiable, with Lipschitz-continuous gradients), at each intersection of linear and quadratic parts. This smoothness is also key in achieving faster convergence guarantees while performing optimization on the non-convex global loss function parametrized with this given shape function, as described in the “3. Inverse Reconstruction” section below.

[0187]

[0163] One such shape variation of system 10 is the huberized piecewise-linear triangular shape, such as is shown in Fig. 12. The first partly -huberized sub-variation is: where δ is the timing of local depolarization, p is the timing of local repolarization, μ is a small positive constant of depolarization duration, and is a tiny positive constant of smoothing duration. Here, M(t) is continuous and smooth everywhere except at t = δ + μ , where the linear upstroke and linear downstroke intersects.

[0188]

[0164] The second fully-huberized sub-variation is:

[0189]

[0190] Here, M(t) is globally continuous and smooth, and is required. An example of this shape is shown in Fig.13.

[0191] STAGE 3 - Inverse reconstruction - solving for the action potential (AP)

[0192]

[0165] As described herein, system 10 can be used to collect a set of voltage measurement inside the heart, outside the heart, or both, and to estimate the action potential (e.g., cardiac action potential) for various locations on the cardiac or other anatomy (e.g., instructions 53 stored in memory 52 of processor 51 are adapted to estimate the action potential). To estimate the action potential, system 10 can utilize any of the forward models described herein, because the lead field is a physics-based model that links the relationship between the actional potentials and measured voltages at the associated electrodes of system 10 (e.g., electrodes 155, patch electrodes 40, or both).

[0193] Approach 1: Iterative method

[0194]

[0166] In this approach, shape and location of action potentials are estimated by system 10 recursively in iterative manner. Fig. 14 is a flow chart that summarizes the algorithmic steps used by system 10 to estimate action potentials (e.g., cardiac action potentials) using the parameterized formulation described in, but not limited to, Stage 2, described hereabove. In these steps, spatial information is incorporated in the first step, while temporal information is used in the remaining steps, each as described below. Step 1: Update action potential (AP) estimation

[0195]

[0167] Given “m” voltage measurements taken over “t” time samples , the action potential (e.g., cardiac action potential) at “n” points on the cardiac or other anatomy can be estimated by system 10 using a composite “cost function” as a sum of data error and regularizations. The data error is || AX — Y|| where A is one of the linearized forward models above. The regularization can be any convex norm-based regularization such as L1 -norm, L2- norm, Frobenius norm, and / or general mixed-norm. The mixed-norm regularization can include mixed matrix norm and can also be generalized to consider both spatial and temporal regularity constraints by multiplying a spatial Laplacian or temporal difference matrix before applying a norm operator. This composite cost function is naturally the sum of a smooth (i.e. gradient Lipschitz continuous) function and a non-smooth proximable function (i.e. proximal mapping can be computed in closed form). This non-smooth proximable function includes general regularizations, such as the indicator function of convex constraint set, and mixed matrix norm. With this cost function, the action potential (e.g., cardiac action potential) can be updated by system 10 using the iterative gradient-based, approach to directly minimize the cost function, or any other nonlinear-constrained optimization approach such as inexact augmented Lagrangian methods (iALM) to find primal-dual solutions that satisfy Karush-Kuhn-Tucker (KKT) conditions. The action potential (e.g., cardiac action potential) update equation can be described as where “g” is the gradient of the smooth objective part, fl is the proximal operator of the non- smooth objective part (which is usually a constrained projection on the norm ball, or a projection to a convex constraint set), 2 is the gradient step size and “i” is the iteration step.

[0196] Step 2: Update slope parameters and translation estimation.

[0197]

[0168] With the most-recent estimation of action potentials (e.g., cardiac action potentials), the shape of the action potential can be separately recovered by system 10 at each point on the associated anatomy (e.g., cardiac anatomy). For each point, initial slope parameters for repolarization can be estimated from the action potential using a look up table of system 10 (e.g., of memory 52 of processing unit 50) that lists the estimated repolarization width corresponding to all possible variations of slope parameters. Since each point on the associated anatomy can have multiple activations over the sampled time “t”, these slope parameters are estimated for each activation separately. System 10 can then derive translation by peak detection on the estimated action potential (e.g., cardiac action potential).

[0198] Step 3: Update local depolarization time(s)

[0199]

[0169] The local time of depolarization can be estimated at every point on the associated anatomy (e.g., cardiac anatomy) using the first exponential term of the parameterized equation hereabove, where first order or second order solvers are used by system 10 to estimate the depolarization time.

[0200] Step 4: Update local repolarization time(s)

[0201]

[0170] Similar to the Step 3, repolarization time for each activation is estimated by system 10 by applying a first order solver for the last two exponential terms of the above parameterized equation.

[0202]

[0171] All of the previous four steps are repeated until the solution is converged.

[0203] Step 5: Integrating action potential duration

[0204]

[0172] Action potential duration is defined as ρ — δ. Since these values are estimated by system 10 for each activation at each point on the associated anatomy (e.g., cardiac anatomy), action potential duration can be calculated easily.

[0205] Approach 2: Multi-Step Method:

[0206]

[0173] The action potential (AP) reconstruction problem can be solved by a multi-step approach. The solution from this method both has a small objective error and is spatial- temporally regular. The main steps include Steps 1 through 4 described herebelow.

[0207]

[0174] In Step 1 , similar to existing approaches, a forward model is computed based on measurement and surface locations.

[0208]

[0175] In Step 2, an interval of time (t) is considered, and a spatial-temporally regularized linear system is solved, for example, with L2 regularization in both spatial Laplacian and temporal difference . Here, unknown X is a matrix of size (n x t), H is the spatial Laplacian matrix, W is the temporal difference matrix, and denotes the Frobenius norm of a matrix. Despite having more regularizations, this problem still can be solved closed form. The interval of time for regular rhythm can be selected as cycle length, or a bit longer than cycle length. For irregular rhythm, the interval of time can be as long as it is needed such as 5 sec, 10 sec or 15 sec.

[0209]

[0176] In Step 3, a shape function is designed. The action potential is parameterized at each point on the cardiac surface through several parameters, and these parameters are estimated. One example of the shape parameters described above includes activation time, APD, and slopes of each phase of the action potential. This shape function can be a product of three sigmoids or any other shape functions defined above: • To estimate these,’ a shap re-fitting process is performed, where F is a shape function, p contains k shape parameters at each cardiac surface location for n locations, R includes additional regularizations, and X0is the inverse solution from previous step). Here, , where is the shape parameter at surface location i, and f is the corresponding surface potential at T time points. For regular rhythm, the shape fitting estimation can be constrained further by knowing the fact that within the interval of time, there is only one action potential. For irregular rhythm, since this shape fitting is applied for each point separately and the shape function has activation time as a parameter, the estimation can be carried out in two different ways: (a) estimate potential number of activations within the interval of time and fit the shape for each activation individually, and / or (b) estimate the potential number of activations within the interval of time and fit the shape for all activation together.

[0210]

[0177] In Step D, shape plus data through a “joint solver” is performed. A spatially regularized data-fitting is represented by: . Here F is the function designed in the previous step. Since this is a large-scale non-convex problem, the previous steps provide a good initial estimation. With this estimation and a non-convex optimization method, not only is error minimized, but also spatial-temporal continuity is significantly enhanced. The recovered parameters give activation time, APD, as well as information about different phases. Approach 3: ML guided approach

[0211] 3-1 Integrated approach

[0212]

[0178] In the integrated approach, any steps of iterative approach or multi-step approach is used along with a machine learning model. The associated training phase and production phase are described immediately herebelow.

[0213]

[0179] In the training phase: (a) activation sequences are generated by running simulation models on realistic tissue and conduction properties, where the activation sequences include one or more types of cardiac arrhythmias; (b) these realistic simulations can be projected to universal atrial or ventricular chamber and / or can be projected onto 2D plane using conformal mapping or similar projection techniques; (c) from the projected data, local activation time and / or other cardiac properties are extracted and considered as training samples; and (d) with these training data, generative models such as GAN, variational encoder, and / or diffusion model are trained to generate local activation time or other cardiac properties.

[0214]

[0180] In the production phase:(a) for a given set of cardiac measurements, the initial local activation time and / or other cardiac properties are estimated; and (b) the initial estimation is iteratively updated by alternatively running one of the steps of the multi-step approach and one or multiple steps of generative model.

[0215]

[0181] In Fig. 15, steps for iterative process during production phase are shown. During each step, the diffusion model denoises the current estimate of activation time. This denoised activation image is projected back to cardiac geometry and the activation time is calibrated and / or denormalized to the sample data. The updated activation time is used to correct action potential data. With the multi-step approach described in approach 1 or approach 2, this correction can be easily made by correcting the parameter that corresponds to the local depolarization time. This updated action potential data is further updated by a single step of the multi-step approach. Then, the estimated activation time is normalized and projected back to the image domain.

[0216]

[0182] Once the residual error is determined to be below a threshold, or when the maximum number of denoising steps for diffusion model is reached, the iterative process is stopped. Fig.16 shows an illustration of this approach with intermediate results. 3-2: Denoising approach

[0217]

[0183] In the training phase: (a) activation sequences are generated by running simulation models on realistic tissue and conduction properties, where the activation sequences include one or more types of cardiac arrhythmias; (b) these realistic simulations can be projected to universal atrial or ventricular chamber and / or can be projected onto 2D plane using conformal mapping or similar projection techniques; (c) from the projected data, local activation time and / or other cardiac properties are extracted and considered as part of the training samples; (d) the other part of training samples is derived from the following: for the given set of activation sequences, multiple measurements are carried out by placing catheter at different locations; for each position, the preferred inversion approach is used to reconstruct the activation time or other cardiac properties; and (e) with these training data, generative models such as GAN, variational encoder or diffusion model and / or other denoising model can be trained to clean the noise or artifacts.

[0218]

[0184] In the production phase:(a) for a given set of cardiac measurements, the local activation time or other cardiac properties are estimated using preferred inversion approach; and (b) these estimates are passed through a generative model and / or denoising model to clean the artifacts or reduce noises.

[0219] 3-3 Direct recovery approach

[0220]

[0185] In the training phase: (a) activation sequences are generated by running simulation models on realistic tissue and conduction properties, where the activation sequences include one or more types of cardiac arrhythmias; (b) these realistic simulations can be projected to universal atrial or ventricular chamber and / or can be projected onto a 2D plane using conformal mapping and / or similar projection techniques; (c) from the projected data, local activation time and / or other cardiac properties are extracted and considered as part of the training samples; (d) the other part of training samples is derived from the following: for the given set of activation sequences, multiple measurements are carried out by placing catheter at different locations; and (e) with these training data, generative models such as GAN, variational encoder and / or diffusion model are trained to estimate local activation time from the measurements.

[0186] In the production phase: (a) the given set of cardiac measurements and geometry are projected to the training setup, and the trained model then is used to generate local activation time or other cardiac properties.

[0221]

[0187] The above-described embodiments should be understood to serve only as illustrative examples; further embodiments are envisaged. Any feature described herein in relation to any one embodiment may be used alone, or in combination with other features described, and may also be used in combination with one or more features of any other of the embodiments, or any combination of any other of the embodiments. Furthermore, equivalents and modifications not described above may also be employed without departing from the scope of the inventive concepts, which are defined in the accompanying claims.

Claims

WHAT IS CLAIMED IS:

1. An action potential mapping system, comprising: a processor for performing an algorithm; a plurality of electrodes, wherein the plurality of electrodes are operatively coupled to the processor and the patient; and a non-transitory computer readable medium storing instructions for the processor to perform the algorithm, the algorithm configured to estimate action potentials, each representative of a plurality of cells by:(a) receiving inputs of a heart chamber anatomy of a patient and spatial coordinates of the plurality of electrodes, and performing forward modeling to produce a lead field;(b) receiving the lead field and receiving a respective plurality of voltage values corresponding to respective voltages detected at the plurality of electrodes;(c) creating an action potential shape model; and(d) performing an inverse solution to produce a plurality of values representing the estimated action potentials.

2. An action potential mapping system according to claim 1, wherein the plurality of electrodes comprises a first plurality of electrodes and a second plurality of electrodes, wherein the first plurality of electrodes are configured to be disposed on respective skin regions of the patient, and wherein the second plurality of electrodes are configured to be disposed within the patient.

3. An action potential mapping system according to claim 1, wherein the plurality of electrodes comprises an electrode array assembly including one or more electrodes of the plurality of electrodes.

4. An action potential mapping system according to claim 3, wherein the electrode array assembly comprises at least one support member, and wherein the at least one support member is constructed and arranged to support the one or more electrodes in a generally ellipsoidal configuration.

5. An action potential mapping system according to claim 1, wherein the processor comprises a non-transitory computer.

6. An action potential mapping system according to claim 1, further comprising a signal processor, wherein the signal processor is operatively coupled between the plurality of electrodes and the processor.

7. An activation potential mapping system according to claim 1, wherein the spatial coordinates of the plurality of electrodes are derived from magnetic navigation, impedance navigation, or both.

8. An action potential mapping system according to claim 1 , wherein at least a part of the processor is disposed remotely from the plurality of electrodes.

9. An action potential mapping system according to claim 1 , wherein the plurality of cells comprises a plurality of cardiac cells.

10. An action potential mapping system according to claim 9, wherein the plurality of cardiac cells comprises a plurality of human cardiac cells.

11. An action potential mapping system according to claim 1 , wherein the plurality of cells comprises a cell type selected from the group consisting of; a bladder cell; a brain cell; a peripheral nerve cell; and combinations thereof.

12. An action potential mapping system according to claim 1, further comprising an anatomy module, wherein the anatomy module is configured to generate patient geometry data.

13. An action potential mapping system according to claim 1 , wherein the plurality of electrodes are spaced apart from one another at a respective distance of no more than 5mm, 3mm, and / or 1mm.

14. An action potential mapping system according to claim 1, wherein the plurality of electrodes are spaced apart from one another at a respective distance of at least 1mm, 3mm, and / or 5mm.

15. An action potential mapping system according to claim 1, further comprising a plurality of magnetic sensors, wherein the plurality of magnetic sensors are operatively coupled to the processor.

16. An action potential mapping system comprising: a processor for performing an algorithm; a plurality of electrodes, the plurality of electrodes are operatively coupled to the processor and the patient; and a non-transitory computer readable medium storing instructions for the processor to perform the algorithm, the algorithm configured to estimate action potentials, each representative of a plurality of cells by:(a) receiving inputs of a heart chamber anatomy of a patient and spatial coordinates of a plurality of electrodes coupled to the patient, and performing forward modeling to produce a lead field;(b) receiving the lead field and receiving a respective plurality of voltage values corresponding to respective voltages detected at the plurality of electrodes; and(c) performing an inverse solution to produce a plurality of values representing the estimated action potentials; wherein the producing of the lead field includes developing a forward model:where S denotes a matrix containing a discretized action potential of a cardiac surface and / or other tissue surface, Y denotes a measurement matrix, forward model matrix A denotes the lead field, wherein the lead field is derived by the equation:where is an unknown action potential, and is a measuredvoltage at the electrode located at r and time t; and wherein the inverse solution includes:(i) reconstructing a shape of a cardiac action potential and / or other action potential by parameterizing the action potential according to:where α, β , γ are constants defining the steepness of the upstroke and downstroke, δ is the timing of locai depolarization, ρ is the timing of local repolarization, and T is the translation parameter;(ii) applying the lead field and the plurality of voltage values;(iii) creating a map of estimated action potentials;(iv) for each point within the action potential map, updating values for slope parameters, translation estimation, local depolarization times and local repolarization times;(v) updating the action potential estimations; and(vi) iterating until convergence to produce the plurality of values representing the estimated action potentials.

17. An action potential mapping system according to claim 16, wherein the plurality of electrodes comprises a first plurality of electrodes and a second plurality of electrodes, wherein the first plurality of electrodes are configured to be disposed on respective skin regions of the patient, and wherein the second plurality of electrodes are configured to be disposed within the patient.

18. An action potential mapping system according to claim 16, wherein the plurality of electrodes comprises an electrode array assembly including one or more electrodes of the plurality of electrodes.

19. An action potential mapping system according to claim 18, wherein the electrode array assembly comprises at least one support member, and wherein the at least one support member is constructed and arranged to support the one or more electrodes in a generally ellipsoidal configuration.

20. An action potential mapping system according to claim 16, wherein the processor comprises a non-transitory computer.

21. An action potential mapping system according to claim 16, further comprising a signal processor, wherein the signal processor is operatively coupled between the plurality of electrodes and the processor.

22. An action potential mapping system according to claim 16, wherein at least a part of the processor is disposed remotely from the plurality of electrodes.

23. An action potential mapping system according to claim 16, wherein the plurality of cells comprises a plurality of cardiac cells.

24. An action potential mapping system according to claim 23, wherein the plurality of cardiac cells comprises a plurality of human cardiac cells.

25. An action potential mapping system according to claim 16, wherein the plurality of cells comprises a cell type selected from the group consisting of: a bladder cell; a brain cell; a peripheral nerve cell; and combinations thereof.

26. An action potential mapping system according to claim 16, further comprising an anatomy module, wherein the anatomy module is configured to generate patient geometry data.

27. An action potential mapping system according to claim 16, wherein the plurality of electrodes are spaced apart from one another at a respective distance of no more than 5mm, 3mm, and / or 1mm.

28. An action potential mapping system according to claim 16, wherein the plurality of electrodes are spaced apart from one another at a respective distance of at least 1mm, 3mm, and / or 5mm.

29. An action potential mapping system according to claim 16, further comprising a plurality of magnetic sensors, wherein the plurality of magnetic sensors are operatively coupled to the processor.

30. An action potential mapping system comprising: a processor for performing an algorithm; a plurality of electrodes, the plurality of electrodes are operatively coupled to the processor and the patient; and a non-transitory computer readable medium storing instructions for the processor to perform the algorithm, the algorithm configured to estimate an action potential representative of a plurality of cells by:(a) receiving inputs of a heart chamber anatotny of a patient and spatial locations of a plurality of electrodes coupled to the patient, and performing forward modeling to produce a lead field;(b) receiving the lead field and receiving a respective plurality of voltage values corresponding to respective voltages detected at the plurality of electrodes; and(c) performing an inverse solution to produce a plurality of values representing the estimated action potentials; wherein the producing of the lead field includes developing a forward model:where S denotes a matrix containing a discretized action potential of the cardiac surface and / or other tissue surface, denotes a 3m × t matrix containing thedirectional derivative of measurements Y with respect to x, y, and z, and forward model matrix A denotes the lead field, wherein the lead field is derived by the equation:where is an unknown action potential, and is the measuredvoltage at the electrode located at r and time t; and wherein the inverse solution includes:(i) recons tructing a shape of a cardiac action potential and / or other action potential by parameterizing the action potential according to:where α, β , γ are constants defining the steepness of the upstroke and downstroke, δ is the timing of local depolarization, ρ is the timing of local repolarization, and τ is the translation parameter;(ii) applying the lead field and the plurality of voltage values;(iii) estimating an action potential map;(iv) for each point within the action potential map, updating values for slope parameters, translation estimation, local depolarization times and local repolarization times;(v) updating the action potential estimations; and(vi) iterating until convergence to produce the plurality of values representing the estimated action potentials.

31. An action potential mapping system according to claim 30, wherein the plurality of electrodes comprises a first plurality of electrodes and a second plurality of electrodes, wherein the first plurality of electrodes are configured to be disposed on respective skin regions of the patient, and wherein the second plurality of electrodes are configured to be disposed within the patient.

32. An action potential mapping system according to claim 30, wherein the plurality of electrodes comprises an electrode array assembly including one or more electrodes of the plurality of electrodes.

33. An action potential mapping system according to claim 32, wherein the electrode array assembly comprises at least one support member, and wherein the at least one support member is constructed and arranged to support the one or more electrodes in a generally ellipsoidal configuration.

34. An action potential mapping system according to claim 30, wherein the processor comprises a non-transitory computer.

35. An action potential mapping system according to claim 30, further comprising a signal processor, wherein the signal processor is operatively coupled between the plurality of electrodes and the processor.

36. An action potential mapping system according to claim 30, wherein at least a part of the processor is disposed remotely from the plurality of electrodes.

37. An action potential mapping system accor ding to claim 30, wherein the plurality of cells comprises a plurality of cardiac cells.

38. An action potential mapping system according to claim 37, wherein the plurality of cardiac cells comprises a plurality of human cardiac cells.

39. An action potential mapping system according to claim 30, wherein the plurality of cells comprises a cell type selected from the group consisting of: a bladder cell; a brain cell; a peripheral nerve cell; and combinations thereof.

40. An action potential mapping system according to claim 30, further comprising an anatomy module, wherein the anatomy module is configured to generate patient geometry data.

41. An action potential mapping system according to claim 30, wherein the plurality of electrodes are spaced apart from one another at a respective distance of no more than 5mm, 3mm, and / or 1mm.

42. An action potential mapping system according to claim 30, wherein the plurality of electrodes are spaced apart from one another at a respective distance of at least 1mm, 3mm, and / or 5mm.

43. An action potential mapping system according to claim 30, further comprising a plurality of magnetic sensors, wherein the plurality of magnetic sensors are operatively coupled to the processor.

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