Waveform delivery based on tissue fiber orientation

Abstract

A medical system is configured to deliver varying pulsed field ablation (PFA) waveforms to a treatment site based on tissue-fiber orientation information. In various examples, the electronic controller of the medical system operates to trigger different PFA waveforms for delivery to different specific locations within the treatment site depending on the predominant cell orientation therein. In some examples, the waveforms selected for delivery in this manner are pre-optimized for the corresponding cell orientation, thereby beneficially reducing the frequency of undesired instances of over-ablation and under-ablation.

Description

Atty Ref. No. A0011420WO01 WAVEFORM DELIVERY BASED ON TISSUE FIBER ORIENTATION FIELD

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No.63 / 621,191, filed January 16, 2024, the entire content of which is incorporated herein by reference. FIELD

[0002] The present disclosure relates to methods, systems, and devices for enhancing the efficiency and efficacy of ablation energy delivery and improving patient safety. BACKGROUND

[0003] Tissue ablation is used in numerous medical procedures to treat a patient. In some examples, ablation procedures involve modification of target tissue, e.g., to stop electrical propagation through the tissue in patients with an arrhythmia. Such ablation procedures are often performed by passing energy, such as electrical energy, through one or more electrodes of an inserted catheter. The energy causes modifications to the target tissue. SUMMARY

[0004] Disclosed herein are, among other things, various examples, aspects, features, and embodiments of a medical system capable of varying pulsed field ablation (PFA) waveforms delivered to a treatment site based on tissue-fiber orientation information. In various examples, the electronic controller of the medical system operates to trigger different PFA waveforms for delivery to different specific locations within the treatment site depending on the predominant cell orientation therein. In some examples, the waveforms selected for delivery in this manner are pre-optimized for the corresponding cell orientation, thereby beneficially reducing the frequency of undesired instances of over-ablation and under-ablation.

[0005] According to one example, a medical method includes generating a first electro-anatomical map of a treatment site having tissue-fiber orientation information.Atty Ref. No. A0011420WO01 The medical method also includes determining a first PFA delivery configuration based on the first electro-anatomical map. The first PFA delivery configuration specifies a first set of electrodes selected from a plurality of electrodes of an ablation device and further specifies a set of parameter values for a first PFA waveform to be delivered to the treatment site via the first set of electrodes. The medical method also includes causing a signal generator to transmit the first PFA waveform to the first set of electrodes.

[0006] According to another example embodiment, provided is a non-transitory computer-readable medium storing instructions that, when executed by a medical system, cause the medical system to perform operations comprising the above medical method.

[0007] According to yet another example, a medical system includes: an electronic controller with an electronic processor; a signal generator controlled by the electronic controller; and an ablation device having a plurality of electrodes connectable to the signal generator. The electronic processor is configured to generate a first electro-anatomical map of a treatment site having tissue-fiber orientation information and to determine a first PFA delivery configuration based on the first electro-anatomical map. The first PFA delivery configuration specifies a first set of electrodes selected from the plurality of electrodes and further specifies a set of parameter values for a first PFA waveform to be delivered to the treatment site via the first set of electrodes. The electronic controller is configured to cause the signal generator to generate and transmit the first PFA waveform to the first set of electrodes. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG.1 is a block diagram illustrating a medical system according to some examples.

[0009] FIG.2 is a block diagram illustrating an ablation device used in the medical system of FIG.1 according to some examples.

[0010] FIGS.3-6 graphically illustrate electrical waveforms used in the medical system of FIG.1 according to some examples.Atty Ref. No. A0011420WO01

[0011] FIG.7 is a flowchart illustrating a medical method implemented using the medical system of FIG.1 according to some examples. DETAILED DESCRIPTION

[0012] Pulsed field ablation (PFA) involves the application of pulsed electric fields (PEFs), which reversibly or irreversibly destabilize cell membranes through electro- permeabilization, but generally do not affect the structural integrity of the tissue components, including the acellular cardiac extracellular matrix. The nature of PFA allows for very brief periods of therapeutic energy delivery, e.g., pulses on the order of tens of milliseconds in duration and pulse trains distributed over several seconds. In at least some examples, PFA does not cause collateral damage to non-targeted tissue as frequently or severely as thermal ablation techniques. Alternatively, pharmacologic agents may be preferentially introduced into the cells of targeted tissue that are exposed to PEF via reversible membrane permeabilization.

[0013] Catheters inserted and navigated through blood vessels are used to probe and treat a variety of medical conditions. For example, atrial fibrillation and other cardiac arrythmias are treated by inserting a catheter into a blood vessel and guiding the end thereof to the heart. The end of the catheter typically has electrodes for applying electrical energy. At least some of the electrodes can be used to detect electrical activity in surrounding tissues and / or to deliver PEF treatment to the tissue.

[0014] As used herein, various instances of the terms “pulse,” “pulsed signal,” and “pulsed electric field” refer to a single pulse or to a train of pulses. In some instances, a single pulse or a train of pulses vary in amplitude over a time interval during which such single pulse or train of pulses exists.

[0015] Cardiac tissue is composed of different types of cells, such as cardiomyocytes, fibroblasts, smooth muscle cells, immune cells, and neuronal cells. Cardiac fibers are long, cylindrical muscle cells with one or two nuclei. Cardiac fibers are arranged in layers of counter-wound helices around the ventricles. The complex structural organization of cardiac fibers and the spatial arrangement of cardiomyocytes in laminar sheetlets significantly contribute to cardiac function and contractile ejection patterns. InformationAtty Ref. No. A0011420WO01 about local cardiac fiber orientation can be obtained, e.g., using diffusion tensor imaging (DTI) with MRI and high frequency ultrasound. For describing the global arrangement, some models depict the left ventricle (LV) myocardial architecture as a transmural continuum between two helical fiber geometries, where right-handed helical geometry in the subendothelial region gradually changes into left-handed geometry in the subepicardial region. Normal human LV architecture comprises a highly aligned array of cardiac fibers whose orientation depends on the transmural location. The spatial relations of the fibers in serial microscopic sections suggest that the LV can be characterized as a cross-inked, fiber- wound, ellipsoidal, or paraboloidal pressure vessel with the fiber angle changing smoothly from approximately 60° at the endocardium to approximately −60° at the epicardium. In the context of cardiac arrhythmia treatment, a wide range of pulse shapes and durations can be used, including but not limited to, exponentially decaying pulses, monophasic pulses, and biphasic pulses.

[0016] The orientation of elongated cardiac cells and various PEF parameters, such as the amplitude, duration, number of pulses, and repetition frequency, typically affect the efficiency of PFA treatment. If the electric field is oriented perpendicular to the myocardial fibers, then those perpendicularly oriented cells are typically more sensitive to shorter (e.g., < 100 ns) pulses, whereas parallel oriented cells are typically more sensitive to longer (e.g., > 10 µs) pulses. This anisotropic sensitivity is believed to be at least partially responsible for relatively large variability of PFA lesion sizes observed for similar tissues treated in different instantiations of a same treatment procedure. In at least some cases, such variability presents a significant challenge to a safe and effective delivery of treatment to patients.

[0017] At least some of the above-indicated problems in the state of the art can beneficially be addressed using various embodiments disclosed herein. For example, in one embodiment, fiber orientation data are obtained from pre-operative magnetic resonance imaging (MRI) data (e.g., MRI-DTI) and those orientation data are subsequently superimposed onto pre-operative magnetic resonance imaging (MRI) data and imported into the mapping and navigation system of the PFA apparatus. The mapping and navigation system is then used to trigger different waveforms for delivery to different specific locations within the treatment site. The waveforms selected for delivery in thisAtty Ref. No. A0011420WO01 manner may be pre-optimized for the corresponding cell orientation, thereby beneficially reducing the above-mentioned lesion-size variability and the associated undesired instances of over-ablation and under-ablation.

[0018] FIG.1 is a block diagram illustrating a medical system 100 according to some examples. The medical system 100 is typically used with one or more ablation devices 110, such as catheters and surgical instruments having PFA capabilities. In the example shown, the medical system 100 includes one ablation device 110. In other examples, the medical system 100 may include two or more ablation devices 110. The medical system 100 also includes a medical apparatus 120, an optional pacing device 130, and a mapping and navigation system 140.

[0019] The medical apparatus 120 includes a signal generator 122, an electronic controller 123, and an optional cardiac stimulator 128. The electronic controller 123 includes a processor 124 and a memory 126. In the example shown, the medical apparatus 120 is coupled to the ablation device 110, the pacing device 130, and the mapping and navigation system 140 as indicated in FIG.1.

[0020] The signal generator 122 is configured to generate electrical waveforms suitable for ablating a target tissue, such as, for example, the left isthmus region of the heart. The signal generator 122 is appropriately electrically connected to the ablation device 110 for delivery of energy to the target tissue. The processor 124 is connected to the memory 126 to read data therefrom and to write data thereto. The processor 124 is also configured to receive digital signals originating from the cardiac stimulator 128, the pacing device 130, and the mapping and navigation system 140. In various examples, the processor 124 performs algorithmic processing of pertinent data to determine one or more parameters for the waveforms to be generated by the signal generator 122. The memory 126 stores instructions that, when executed by the processor 124, cause the signal generator 122 to execute various modules, processes, and functions, such as PFA waveform generation operations in accordance with the determined parameters, cardiac pacing synchronization, and electrode tracking and visualization.

[0021] In some examples, the ablation device 110 is a catheter or a surgical instrument configured to receive electrical waveforms from the signal generator 122 and deliver theAtty Ref. No. A0011420WO01 corresponding energy to the target tissue. During a medical procedure, the ablation device 110 is manipulated and positioned such that one or more electrodes 112 thereof are near the target tissue. The electronic controller 123 causes the signal generator 122 to generate and transmit selected waveforms to the one or more electrodes 112 which deliver the corresponding energy to the target tissue. In one example, different ones of the electrodes 112 are independently connectable to the signal generator 122, with each electrode 112 including a respective insulated electrical lead designed to sustain a voltage of greater than about 500 V without a dielectric breakdown in the insulation. In some examples, the electrical insulation on each of the electrical leads is selected such that an electrical potential difference of about 4 kV across its thickness does not cause a dielectric breakdown therein. In some examples, the electronic controller 123 runs a suitable algorithm to automatically make decisions on vectoring and waveform selections given specific tissue thickness and fiber orientation data and then operates the signal generator 122 accordingly.

[0022] One illustrative example of the ablation device 110 is described in more detail below in reference to FIG.2. Based on the provided description, a person of ordinary skill in the pertinent art will be able to select and use with the medical system 100 other suitable types of ablation device 110 in accordance with various embodiments disclosed herein without any undue experimentation.

[0023] When present, the pacing device 130 is suitably coupled to a patient (not explicitly shown in FIG.1) and configured to receive a heart pacing signal from the cardiac stimulator 128 for patient’s cardiac stimulation. In some examples, an indication for the pacing signal is transmitted by the cardiac stimulator 128 to the electronic controller 123. Based on the indication, the processor 124 and the memory 126 are operated by the electronic controller 123 to select, compute, or otherwise identify a pacing pulse waveform. The electronic controller 123 then causes the signal generator 122 to generate that pacing pulse waveform and transmit it, via the cardiac stimulator 128, to the pacing device 130 in proper synchronization with the cardiac cycle.

[0024] The mapping and navigation system 140 is used for guiding a medical procedure. In the example shown, the mapping and navigation system 140 is coupled (e.g., eitherAtty Ref. No. A0011420WO01 physically or communicatively) to the medical apparatus 120. In some other examples, the mapping and navigation system 140 is integrated into the medical apparatus 120. The mapping and navigation system 140 is designed to help visualize the real-time position and orientation of catheters, ablation devices, and / or auxiliary devices within the patient’s body, e.g., to increase the accuracy of targeted ablation and reacquisition of pacing sites for re-ablation. In various implementations, the mapping and navigation system 140 enables one or both of impedance-based tracking and electromagnetic tracking.

[0025] In one example, the mapping and navigation system 140 operates to generate an electro-anatomical map of the treatment site using a mapping catheter 146. In some examples, the mapping catheter 146 is integrated into the ablation device 110. In some other examples, the mapping catheter 146 is a dedicated mapping catheter that is separate from the ablation device 110. The mapping and navigation system 140 determines and tracks the position and / or orientation of the ablation device 110. For example, the mapping and navigation system 140 may determine the position of an electromagnetic (EM) sensor referenced to the tracked ablation device 110 using three or more magnetic sources of a magnetic-field generator 142 as references. The magnetic sources of the magnetic field generator 142 are positioned such that a volume of magnetic fields 144 generated thereby envelopes the mapping catheter 146, the tracked portion of the ablation device 110, or an auxiliary device having the corresponding EM sensor. The magnetic fields in that volume are calibrated and can be controlled with the electronic controller 123. Based on the response of the EM sensor to such magnetic fields, position of the tracked portion is accurately determined and tracked in real time. With the tracked location information, a visual representation of the ablation device 110 or auxiliary device is displayed on an anatomical map, e.g., to provide spatial and anatomic context for visualizing the electrode locations. Such visual representations can be generated, e.g., using the processor 124 or another processing device coupled to or integrated into the medical apparatus 120 or the mapping and navigation system 140.

[0026] In various additional examples, the mapping and navigation system 140 may, alternatively or additionally, employ impedance-based mapping / navigation techniques and / or hybrid EM mapping / navigation (e.g., magnetic and impedance based) techniques.Atty Ref. No. A0011420WO01 In further examples, the mapping and navigation system 140 can be configured to use ultrasound- and / or MR-based navigation.

[0027] In some examples, the ablation device 110 includes an actuation mechanism 116, e.g., a knob, a lever, a handle, or other suitable mechanism for moving, deflecting, steering, reconfiguring, deploying, and otherwise manipulating the ablation device 110 or relevant portions thereof within the patient’s anatomy (also see FIG.2). The actuation mechanism 116 can be controlled by an operator based on the location of the distal portion of the ablation device 110 and the overall objective of the medical procedure. In some examples, the operator controls the actuation mechanism 116 with the aid of the above- mentioned visual representations generated with the mapping and navigation system 140, e.g., based in part on the signals received from one or more sensors 114 of the ablation device 110.

[0028] FIG.2 is a block diagram illustrating the ablation device 110 according to some examples. In the example shown, the ablation device 110 is a catheter having a proximal portion 228 and a distal portion 236. The proximal portion 228 is connected to the medical apparatus 120 as indicated in FIGS.1-2. An enlarged view of the distal portion 236 is shown in FIG.2 to illustrate certain components thereof more clearly.

[0029] The distal portion 236 of the catheter 110 in this example has nine electrodes 112, which are labeled 1121-1129. In different respective operating modes of the medical system 100, the electrodes 1121-1129are used to deliver pulsed waveforms to the treatment site, to sense mapping / navigation (MAP / NAV) signals at the treatment site, and / or to collect electrogram (EGM) signals from the treatment site. The catheter 110 also includes an elongated body 234 to enable placement of the electrodes 112 in proximity to the treatment site of the patient. The elongated body 234 typically includes one or more lumens that provide mechanical, electrical, and / or fluid communication between the proximal portion 228 and the distal portion 236 of the catheter 110. In some examples, the elongated body 234 has a central or guidewire lumen for hosting a shaft 238 and a carrier arm 240 in a retracted position. The shaft 238 is movable along the central lumen. In operation, longitudinal movement of the shaft 238 is used to cause the carrier arm 240 to transition between at least a first (e.g., substantially linear) configuration and a secondAtty Ref. No. A0011420WO01 (e.g., looped) configuration. As an illustration, FIG.2 shows the carrier arm 240 in a looped configuration.

[0030] The electrodes 1121-1129are located on the carrier arm 240. Each one of the electrodes 1121-1129is electrically connected, via a dedicated electrical wire of an electrical bus disposed within the corresponding lumen of the elongated body 234, to a multi-pin connector (not explicitly shown) located at the end of the proximal portion 228 of the catheter 110. The multi-pin connector is further electrically connected to the medical apparatus 120.

[0031] FIG.3 graphically illustrates an electrical waveform 302 generated with the signal generator 122 according to some examples. The electrical waveform 302 includes a sequence of biphasic pulses 310, each including a respective positive pulse 322 and a respective negative pulse 324. As would be understood by one of ordinary skill in the art, whether a pulse is positive or negative may be understood to be a matter of perspective (e.g., from the perspective of one electrode or another), such that in some embodiments the same biphasic pulse delivered to the same set of electrodes may be viewed as having the positive pulse 322 first or the negative pulse 324 first depending upon this perspective. In the example shown, each pulse 322, 324 has an absolute amplitude value αV0and a pulse width Tp, where V0is a constant. Both the scaling factor α and the pulse width Tpare selectable and controllable via the electronic controller 123.

[0032] The time delay between the positive pulse 322 and the negative pulse 324 of the same biphasic pulse 310 is d1. The parameter d1is often referred to as the interphase delay. The time delay between two consecutive biphasic pulses 310 in the waveform 302 is d2. The parameter d2is often referred to as the inter-pulse delay. The waveform 302 has a period Tw= d1+ d2+ 2Tp. In some examples, the period Twis on the order of milliseconds. In general, the waveform 302 has N biphasic pulses 310, where N is a positive integer. The parameters N, d1, d2, and Twof the waveform 202 are also selectable and controllable via the electronic controller 123. In some examples, the interphase delay may nominally have a zero value. Further, the illustrated waveform is just one example, and more complex waveforms (e.g. tri-phasic) may be constructed and used in various additional examples.Atty Ref. No. A0011420WO01

[0033] In some examples, one or more of the following considerations are applied when configuring the signal generator 122 for delivery of therapeutic waveforms: i. Biphasic or other balanced waveforms, such as the waveform 302, are characterized by an approximately zero net charge applied to the targeted tissue, which is beneficial for many treatment scenarios. ii. The value of αV0is selected to produce an electric field strength in the range between approximately 250 V / cm and 1250 V / cm in the vicinity of the corresponding electrodes 112. This electric field strength corresponds to the irreversible electroporation threshold of a specific targeted tissue, in this example, cardiac myocytes. The value of αV0may differ for different ablation applications targeting different tissues. These electric field strengths can typically be produced with an applied voltage in the range from approximately 1 kV to approximately 4 kV. iii. Substantially rectangular pulses 322, 324 with a short rise time and a short fall time are often preferred for therapeutic pulses to achieve an approximately maximum field strength for substantially entire pulse duration. iv. Biphasic pulses 310 may be delivered in trains. v. Pulse trains are typically delivered within a relatively short time interval, e.g., shorter than 200 ms, to fit into the refractory period of the surrounding myocardium. The interphase delay and / or the inter-pulse delay can be adjusted to achieve a desired train duration. vi. Therapeutic pulses may be vectored between the electrodes that are selected to produce a therapeutic electric field strength and orientation into the targeted volume of tissue. In different examples, such electrodes can be on a same catheter, on multiple catheters, or among catheter and surface / patch electrodes.

[0034] FIG.4 graphically illustrates an electrical waveform 402 generated with the signal generator 122 according to another example. The waveform 402 is a concatenation of two waveform segments 302 (also see FIG.3), which are labeled 3021and 3022, respectively. The waveform 402 is switched from the waveform segment 3021to the waveform segmentAtty Ref. No. A0011420WO01 3022at the time t=t1. The waveform segments 3021and 3022differ from one another in the values of their respective pulse widths Tp1and Tp2, where Tp1>Tp2.

[0035] Segmented electrical waveforms, of which the waveform 402 is an example, are useful when the tissue volume subjected to the corresponding electric field has a mixture of differently oriented fibers or cells. For example, when the tissue volume has 10% of parallel-oriented cells and 90% of perpendicular-oriented cells, the segment 3021may contain 90% of the total number of pulses with the pulse width being in the 1-50 µs range, and the segment 3022may contain 10% of the total number of pulses with the pulse width being in the 100 ns - 1 µs range. Similarly, when the tissue volume has 50% of parallel- oriented cells and 50% of perpendicular-oriented cells, the pulse distribution between the segments 3021and 3022may be 50%:50%. In some examples, all pulses are in a pulse width range corresponding to little or no sensitivity to the fiber orientation (e.g., 1-5 µs).

[0036] In some cases, an increase in the electric field strength renders perpendicular cells more susceptible to electric fields. Therefore, in some examples, increasing the electric field strength may be useful as it may result in preferential ablation of perpendicular cells.

[0037] In some examples, a segmented electrical waveform may have more than two segments. For example, in some cases, a pulse-width sweep can be implemented using different segments of such segmented electrical waveform. As another example, suppose that the tissue volume has 30% of parallel-oriented cells, 40% of slanted cells, and 30% of perpendicular-oriented cells. In this case, the segmented electrical waveform may be constructed to have three segments, with the respective pulse widths being selected to match the volume’s composition.

[0038] FIG.5 graphically illustrates a biphasic pulse 510 generated with the signal generator 122 according to yet another example. The biphasic pulse 510 includes a positive pulse 522 and two negative pulses 5241, 5242. The pulse width of the positive pulse 522 is two times larger than the pulse width of each of the negative pulses 5241, 5242. Due to this property, the biphasic pulse 510 applies an approximately zero net charge to the targeted tissue. A plurality of biphasic pulse 510 can be applied in sequence to form a pulse sequence qualitatively similar to the waveform 302.Atty Ref. No. A0011420WO01

[0039] FIG.6 graphically illustrates a biphasic pulse 610 generated with the signal generator 122 according to yet another example. The biphasic pulse 610 includes a positive pulse 622 and four negative pulses 6241-6244. The pulse width of the positive pulse 622 is four times larger than the pulse width of each of the negative pulses 6241- 6244. Due to this property, the biphasic pulse 610 applies an approximately zero net charge to the targeted tissue. A plurality of biphasic pulse 610 can be applied in sequence to form a pulse sequence qualitatively similar to the waveform 302.

[0040] FIG.7 is a flowchart illustrating a medical method 700 implemented using the medical system 100 according to some examples. The method 700 is described below in continuing reference to FIGS.1-7.

[0041] The method 700 includes generating an electro-anatomical map of the treatment site (in a block 702). In various examples of the block 702, the electro-anatomical map is generated using the mapping catheter 146 of the mapping and navigation system 140. The mapping and navigation system 140 operates to associate anatomical structure and electrophysiological data collected using the mapping catheter 146 and then displays the combined information in a conveniently readable, visual fashion. When the mapping catheter 146 is moved in the three-dimensional (3D) space, the catheter location is monitored by the mapping and navigation system 140, typically with a spatial resolution of < 1 mm. By gating the acquisition of points in the 3D space to the cardiac electrical activity, data points that represent both location and the electrical activity at that location are acquired by the mapping and navigation system 140 and displayed on a computer screen. After acquiring a sufficient number of data points, a 3D representation (map) of the treatment site is constructed and may be rotated thereafter on the computer screen to provide any selected viewing projection. In various examples, the 3D representation of the treatment site generated in the block 702 is useful for defining the mechanisms of arrhythmias, designing ablation strategies, guiding ablations, and improving the safety of mapping and ablation procedures by allowing localization of critical cardiac structures.

[0042] In some examples, operations of the block 702 include (i) defining the chamber anatomy, (ii) recording signal morphology, timing, and voltage, (iii) displaying the electrical information as color-coded maps, and (iv) annotating and interpreting the mapsAtty Ref. No. A0011420WO01 to delineate the arrhythmia mechanism, in isolation or in combination with other pertinent information, e.g., as the tissue-fiber orientation information described below. Example electro-anatomical data obtained via these operations include chamber reconstruction, tagging of important anatomic landmarks / features and planned or previous ablation lesions, display of diagnostic and mapping catheters, activation mapping, and voltage (or scar) mapping. In some examples, additional specialized features may be available for implementing various additional operations in the block 702, such as enhanced ability to map non-sustained or hemodynamically unstable arrhythmias, ability to display catheter positions, and compatibility with a variety of ablation devices 110.

[0043] The method 700 also includes obtaining a tissue-fiber orientation map of the treatment site (in a block 704). In some examples, the tissue-fiber orientation map is obtained based on pre-procedural imaging data (e.g., MRI-DTI) and / or intraprocedural imaging data (e.g., high frequency ultrasound). In some examples, the tissue-fiber orientation map is imported from an external source in a format compatible with the electro-anatomical map generated in the block 702. One representative example of such format is the DICOM file format, where the acronym DICOM stands for Digital Imaging and Communications in Medicine. In various examples, a tissue-fiber orientation map of the treatment site is constructed based on one or more of the following: computerized tomography (CT) scan data, MRI images of the treatment site, ultrasound images of the treatment site, EGM propagation data, and intracardiac echocardiography (ICE) images of the treatment site.

[0044] In some cases, pre-procedural and intraprocedural imaging data suitable for obtaining a tissue-fiber orientation map of the treatment site may not be available. In such cases, the tissue-fiber orientation map of the treatment site is obtained in the block 704 using a generic model of the heart constructed based on a plurality of reference measurements providing an adequate sampling of the patient population. In some examples, the generic model may be appropriately scaled to better correspond to the electro-anatomical map generated in the block 702. In some cases, the scaling operations include (i) appropriately aligning selected anatomic landmarks or features of the electro- anatomical map of the treatment site generated in the block 702 and a generic tissue-fiber orientation map obtained from the generic model and (ii) applying to the generic tissue-Atty Ref. No. A0011420WO01 fiber orientation map one, two, or three scaling factors corresponding to the three respective spatial dimensions such that the resulting scaled tissue-fiber orientation map has at least three anatomic landmarks or features overlapped with the corresponding anatomic landmarks / features of the electro-anatomical map generated in the block 702.

[0045] The method 700 also includes generating an enhanced electro-anatomical map (in a block 706). The enhanced electro-anatomical map of the block 706 differs from a conventional electro-anatomical map in that it additionally has tissue-fiber orientation information incorporated therein. In some examples, the enhanced electro-anatomical map is generated in the block 706 by combining or fusing the electro-anatomical map generated in the block 702 and the tissue-fiber orientation map obtained in the block 704.

[0046] The method 700 also includes positioning or repositioning the distal portion (e.g., 236, FIG.2) of the ablation device 110 in a selected location at the treatment site (in a block 708). Example operations of the block 708 include the user operating the actuation mechanism 116 of the ablation device 110 and observing, e.g., on the display screen of the medical system 100, the position / orientation of the distal portion of the ablation device 110 on the electro-anatomical map of the treatment site.

[0047] The method 700 also includes the electronic controller 123 determining an optimal PFA delivery configuration (in a block 710). In some examples, operations of the block 710 include the electronic controller 123 running an optimization algorithm using which the optimal PFA treatment configuration is selected. Example inputs to the optimization algorithm include: (i) position and orientation of the distal portion of the ablation device 110 obtained in the block 708; (ii) the enhanced electro-anatomical map of the block 706; and (iii) the planned lesion geometry, including the size, shape, and configuration of the lesion(s). Example outputs of the optimization algorithm include: (i) identification of a set of the electrodes 112 for delivery of a PFA waveform to the treatment site and (ii) a set of parameters defining that PFA waveform.

[0048] In some examples of the optimization algorithm of the block 710, different candidate sets of the electrodes 112 and the corresponding candidate waveforms are evaluated using an appropriately constructed cost function. For each candidate set of the electrodes 112, a respective set of optimal waveform parameters is determined byAtty Ref. No. A0011420WO01 minimizing the cost function. The set of waveform parameters that may be determined in this manner includes some or all of: (i) one or more pulse widths; (ii) one or more amplitude scaling factors α; (iii) one or more values of the interphase delay; (iv) one or more values of the inter-pulse delay; (v) the number of pulses; and (vi) the number of concatenated waveform segments that differ in at least one waveform parameter. Nonlimiting examples of the waveforms that may be considered and evaluated via the optimization algorithm are illustrated in and described in reference to FIGS.3-6. The PFA-configuration evaluations performed in this manner produce a respective minimum cost-function value for each of the candidate sets of the electrodes 112. The candidate set of the electrodes 112 characterized by the smallest cost-function value and the corresponding optimal PFA waveform are then selected to be in the output of the optimization algorithm of the block 710.

[0049] In a representative example, the cost function employed by the optimization algorithm of the block 710 is computed at least based on: (i) the tissue-fiber orientation information found in the enhanced electro-anatomical map of the block 706; (ii) relative orientation of the electric field that would be generated by the candidate set of the delivery electrodes 112 and the tissue fibers subjected to that electric field; and (iii) the orientation- dependent sensitivity of the tissue fibers to the electric field. In some examples, additional factors included into the cost function take into account the relative proximity of the candidate set of the delivery electrodes 112 to certain sensitive anatomic structures, such as the esophagus and the phrenic nerve. In some examples, the orientation-dependent sensitivity of the tissue fibers to the electric field is obtained by submitting an appropriate query to a database having stored therein the corresponding calibration data. Example methods of obtaining such calibration data are described, e.g., in Maria Scuderi, Janja Dermol-Černe, Tina Batista Napotnik, et al., “Characterization of Experimentally Observed Complex Interplay between Pulse Duration, Electrical Field Strength, and Cell Orientation on Electroporation Outcome Using a Time-Dependent Nonlinear Numerical Model,” Biomolecules, 2023, v.13(5), pp.727-746, which is incorporated herein by reference in its entirety.

[0050] The method 700 also includes the electronic controller 123 determining whether the PFA delivery configuration selected with the above-described optimization algorithmAtty Ref. No. A0011420WO01 is acceptable (in a decision block 712). In some examples, this determination is made by comparing the cost-function value of the optimal PFA delivery configuration found via the optimization algorithm of the block 710 with a threshold value. When the cost-function value is smaller than the threshold value (“Yes” at the decision block 712), the processing of the method 700 is directed to a block 714. When the cost-function value is larger than the threshold value (“No” at the decision block 712), the processing of the method 700 is directed back to the block 708.

[0051] Operations of the block 714 include the electronic controller 123 configuring and causing the signal generator 122 to deliver the optimal PFA waveform determined in the block 710 to the treatment site via the corresponding set of the electrodes 112 of the ablation device 110.

[0052] The method 700 also includes the electronic controller 123 determining whether the distal portion of the ablation device 110 needs to be moved to a next position (in a decision block 716). In some examples, this determination of the block 716 is made based on the planned lesion configuration and the already accomplished PFA deliveries in the previous instances of the block 714. When it is determined that the intended lesion configuration has not yet been achieved (“Yes” at the decision block 716), the processing of the method 700 is directed back to the block 708. When it is determined that the intended lesion configuration has been achieved (“No” at the decision block 716), the method 700 is terminated.

[0053] According to an example embodiment disclosed above, e.g., in the summary section and / or in reference to any one or any combination of some or all of FIGS.1-7, provided is a medical method comprising: generating a first electro-anatomical map of a treatment site, the first electro-anatomical map including tissue-fiber orientation information; determining a first pulsed field ablation (PFA) delivery configuration based on the first electro-anatomical map, the first PFA delivery configuration specifying a first set of electrodes selected from a plurality of electrodes of an ablation device and further specifying a set of parameter values for a first PFA waveform to be delivered to the treatment site via the first set of electrodes; and causing a signal generator to generate the first PFA waveform and transmit this PFA waveform to the first set of electrodes.Atty Ref. No. A0011420WO01

[0054] In some embodiments of the above method, the generating includes: generating a second electro-anatomical map of the treatment site based on cardiac electrical activity data collected from the treatment site with a mapping catheter; obtaining a tissue-fiber orientation map corresponding to the treatment site; and combining the second electro- anatomical map and the tissue-fiber orientation map to generate the first electro- anatomical map of the treatment site.

[0055] In some embodiments of any of the above methods, the obtaining includes obtaining the tissue-fiber orientation map based on imaging data corresponding to the treatment site, the imaging data being selected from the group consisting of: computerized tomography scan data; magnetic resonance imaging data; ultrasound imaging data; electrogram propagation data; and intracardiac echocardiography imaging data.

[0056] In some embodiments of any of the above methods, the obtaining includes: aligning a selected set of anatomic landmarks of the second electro-anatomical map with a corresponding set of anatomic landmarks of a generic tissue-fiber orientation map corresponding to the treatment site; and applying to the generic tissue-fiber orientation map one, two, or three scaling factors corresponding to three respective spatial dimensions such that a resulting scaled tissue-fiber orientation map has the corresponding set of anatomic landmarks overlapped with the selected set of anatomic landmarks of the second electro-anatomical map.

[0057] In some embodiments of any of the above methods, the determining includes: running an optimization algorithm to determine a candidate PFA delivery configuration; and comparing a cost-function value corresponding to the candidate PFA delivery configuration with a threshold value to determine whether to use the candidate PFA delivery configuration as the first PFA delivery configuration.

[0058] In some embodiments of any of the above methods, the method further comprises: when the cost-function value is greater than the threshold value, issuing an instruction to move the plurality of electrodes with respect to the treatment site.Atty Ref. No. A0011420WO01

[0059] In some embodiments of any of the above methods, the method further comprises: in response to the plurality of electrodes having been moved, running the optimization algorithm to determine another candidate PFA delivery configuration.

[0060] In some embodiments of any of the above methods, the optimization algorithm is configured to evaluate a plurality of PFA delivery configurations based on respective cost-function values; and wherein any individual one of the plurality of PFA delivery configurations differs from any other one of the plurality of PFA delivery configurations in at least one of an electrode selection and a parameter value of a corresponding PFA waveform.

[0061] In some embodiments of any of the above methods, a set of inputs to the optimization algorithm includes: present positions of the plurality of electrodes at the treatment site; the first electro-anatomical map; and a planned lesion geometry.

[0062] In some embodiments of any of the above methods, the set of parameter values includes one or more of: a pulse width; a pulse amplitude; an interphase delay; an inter- pulse delay; a number of pulses; and a number of waveform segments that differ from one another in at least one waveform parameter value.

[0063] According to another example embodiment disclosed above, e.g., in the summary section and / or in reference to any one or any combination of some or all of FIGS.1-7, provided is a non-transitory computer-readable medium storing instructions that, when executed by a medical system, cause the medical system to perform operations comprising any one of the above methods.

[0064] According to yet another example embodiment disclosed above, e.g., in the summary section and / or in reference to any one or any combination of some or all of FIGS.1-7, provided is a medical system, comprising: an electronic controller including an electronic processor; a signal generator controlled by the electronic controller; and an ablation device including a plurality of electrodes connectable to the signal generator, wherein the electronic processor is configured to: generate a first electro-anatomical map of a treatment site, the first electro-anatomical map including tissue-fiber orientation information; and determine a first pulsed field ablation (PFA) delivery configuration basedAtty Ref. No. A0011420WO01 on the first electro-anatomical map, the first PFA delivery configuration specifying a first set of electrodes selected from the plurality of electrodes and further specifying a set of parameter values for a first PFA waveform to be delivered to the treatment site via the first set of electrodes; and wherein the electronic controller is configured to cause the signal generator to generate and transmit the first PFA waveform to the first set of electrodes, wherein the first PFA waveform is one of a plurality of PFA waveforms that the signal generator is configured to generate.

[0065] In some embodiments of the above system, the system further comprises a mapping and navigation system coupled to the electronic controller and including a mapping catheter, wherein the electronic processor is further configured to: generate a second electro-anatomical map of the treatment site based on cardiac electrical activity data collected from the treatment site with the mapping catheter; obtain a tissue-fiber orientation map corresponding to the treatment site; and combine the second electro- anatomical map and the tissue-fiber orientation map to generate the first electro- anatomical map of the treatment site.

[0066] In some embodiments of any of the above systems, the electronic processor is further configured to obtain the tissue-fiber orientation map based on imaging data corresponding to the treatment site, the imaging data being selected from the group consisting of: computerized tomography scan data; magnetic resonance imaging data; ultrasound imaging data; electrogram propagation data; and intracardiac echocardiography imaging data.

[0067] In some embodiments of any of the above systems, the electronic processor is further configured to: align a selected set of anatomic landmarks of the second electro- anatomical map with a corresponding set of anatomic landmarks of a generic tissue-fiber orientation map corresponding to the treatment site; and apply to the generic tissue-fiber orientation map one, two, or three scaling factors corresponding to three respective spatial dimensions such that a resulting scaled tissue-fiber orientation map has the corresponding set of anatomic landmarks overlapped with the selected set of anatomic landmarks of the second electro-anatomical map.Atty Ref. No. A0011420WO01

[0068] In some embodiments of any of the above systems, the electronic processor is further configured to: run an optimization algorithm to determine a candidate PFA delivery configuration; and compare a cost-function value corresponding to the candidate PFA delivery configuration with a threshold value to determine whether to use the candidate PFA delivery configuration as the first PFA delivery configuration.

[0069] In some embodiments of any of the above systems, the electronic controller is further configured to issue an instruction to move the plurality of electrodes with respect to the treatment site when the cost-function value is greater than the threshold value.

[0070] In some embodiments of any of the above systems, wherein the electronic processor is further configured to run the optimization algorithm to determine another candidate PFA delivery configuration in response to the plurality of electrodes having been moved.

[0071] In some embodiments of any of the above systems, the optimization algorithm is configured to evaluate a plurality of PFA delivery configurations based on respective cost-function values; and wherein any individual one of the plurality of PFA delivery configurations differs from any other one of the plurality of PFA delivery configurations in at least one of an electrode selection and a parameter value of a corresponding PFA waveform.

[0072] In some embodiments of any of the above systems, a set of inputs to the optimization algorithm includes: present positions of the plurality of electrodes at the treatment site; the first electro-anatomical map; and a planned lesion geometry.

[0073] In some embodiments of any of the above systems, the set of parameter values includes one or more of: a pulse width; a pulse amplitude; an interphase delay; an inter- pulse delay; a number of pulses; and a number of waveform segments that differ from one another in at least one waveform parameter value.

[0074] With regard to the processes, systems, methods, heuristics, etc. described herein, it should be understood that, although the steps of such processes, etc. have been described as occurring according to a certain ordered sequence, such processes could be practiced with the described steps performed in an order other than the order describedAtty Ref. No. A0011420WO01 herein. It further should be understood that certain steps could be performed simultaneously, that other steps could be added, or that certain steps described herein could be omitted. In other words, the descriptions of processes herein are provided for the purpose of illustrating certain implementations and should in no way be construed to limit the claims.

[0075] Accordingly, it is to be understood that the above description is intended to be illustrative and not restrictive. Many embodiments and applications other than the examples provided would be apparent upon reading the above description. The scope should be determined, not with reference to the above description, but should instead be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. It is anticipated and intended that future developments will occur in the technologies discussed herein, and that the disclosed systems and methods will be incorporated into such future embodiments. In sum, it should be understood that the application is capable of modification and variation.

[0076] All terms used in the claims are intended to be given their broadest reasonable constructions and their ordinary meanings as understood by those knowledgeable in the technologies described herein unless an explicit indication to the contrary in made herein. In particular, use of the singular articles such as “a,” “the,” “said,” etc. should be read to recite one or more of the indicated elements unless a claim recites an explicit limitation to the contrary.

[0077] Unless explicitly stated otherwise, each numerical value and range should be interpreted as being approximate as if the word “about” or “approximately” preceded the value or range.

[0078] The use of figure numbers and / or figure reference labels (if any) in the claims is intended to identify one or more possible embodiments of the claimed subject matter in order to facilitate the interpretation of the claims. Such use is not to be construed as necessarily limiting the scope of those claims to the embodiments shown in the corresponding figures.Atty Ref. No. A0011420WO01

[0079] Although the elements in the following method claims, if any, are recited in a particular sequence with corresponding labeling, unless the claim recitations otherwise imply a particular sequence for implementing some or all of those elements, those elements are not necessarily intended to be limited to being implemented in that particular sequence.

[0080] Reference herein to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment can be included in at least one embodiment of the disclosure. The appearances of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments necessarily mutually exclusive of other embodiments. The same applies to the term “implementation.”

[0081] Unless otherwise specified herein, the use of the ordinal adjectives “first,” “second,” “third,” etc., to refer to an object of a plurality of like objects merely indicates that different instances of such like objects are being referred to, and is not intended to imply that the like objects so referred-to have to be in a corresponding order or sequence, either temporally, spatially, in ranking, or in any other manner.

[0082] Unless otherwise specified herein, in addition to its plain meaning, the conjunction “if” may also or alternatively be construed to mean “when” or “upon” or “in response to determining” or “in response to detecting,” which construal may depend on the corresponding specific context. For example, the phrase “if it is determined” or “if [a stated condition] is detected” may be construed to mean “upon determining” or “in response to determining” or “upon detecting [the stated condition or event]” or “in response to detecting [the stated condition or event].”

[0083] Throughout the detailed description, the drawings, which are not to scale, are illustrative only and are used in order to explain, rather than limit the disclosure. The use of terms such as height, length, width, top, bottom, is strictly to facilitate the description of the embodiments and is not intended to limit the embodiments to a specific orientation. For example, height does not imply only a vertical rise limitation, but is used to identify one of the three dimensions of a three-dimensional structure as shown in the figures. SuchAtty Ref. No. A0011420WO01 "height" would be vertical where the electrodes are horizontal but would be horizontal where the electrodes are vertical, and so on. Similarly, while all figures show the different layers as horizontal layers such orientation is for descriptive purpose only and not to be construed as a limitation.

[0084] Also, for purposes of this description, the terms “couple,” “coupling,” “coupled,” “connect,” “connecting,” or “connected” refer to any manner known in the art or later developed in which energy is allowed to be transferred between two or more elements, and the interposition of one or more additional elements is contemplated, although not required. Conversely, the terms “directly coupled,” “directly connected,” etc., imply the absence of such additional elements. The same type of distinction applies to the use of terms “attached” and “directly attached,” as applied to a description of a physical structure. For example, a relatively thin layer of adhesive or other suitable binder can be used to implement such “direct attachment” of the two corresponding components in such physical structure.

[0085] The described embodiments are to be considered in all respects as only illustrative and not restrictive. In particular, the scope of the disclosure is indicated by the appended claims rather than by the description and figures herein. All changes that come within the meaning and range of equivalency of the claims are to be embraced within their scope.

[0086] The functions of the various elements shown in the figures, including any functional blocks labeled as “processors” and / or “controllers,” may be provided through the use of dedicated hardware as well as hardware capable of executing software in association with appropriate software. When provided by a processor, the functions may be provided by a single dedicated processor, by a single shared processor, or by a plurality of individual processors, some of which may be shared. Moreover, explicit use of the term “processor” or “controller” should not be construed to refer exclusively to hardware capable of executing software, and may implicitly include, without limitation, digital signal processor (DSP) hardware, network processor, application specific integrated circuit (ASIC), field programmable gate array (FPGA), read only memory (ROM) for storing software, random access memory (RAM), and nonvolatile storage. Other hardware,Atty Ref. No. A0011420WO01 conventional and / or custom, may also be included. Similarly, any switches shown in the figures are conceptual only. Their function may be carried out through the operation of program logic, through dedicated logic, through the interaction of program control and dedicated logic, or even manually, the particular technique being selectable by the implementer as more specifically understood from the context.

[0087] As used in this application, the term “circuitry” may refer to one or more or all of the following: (a) hardware-only circuit implementations (such as implementations in only analog and / or digital circuitry); (b) combinations of hardware circuits and software, such as (as applicable): (i) a combination of analog and / or digital hardware circuit(s) with software / firmware and (ii) any portions of hardware processor(s) with software (including digital signal processor(s)), software, and memory(ies) that work together to cause an apparatus, such as a mobile phone or server, to perform various functions); and (c) hardware circuit(s) and or processor(s), such as a microprocessor(s) or a portion of a microprocessor(s), that requires software (e.g., firmware) for operation, but the software may not be present when it is not needed for operation.” This definition of circuitry applies to all uses of this term in this application, including in any claims. As a further example, as used in this application, the term circuitry also covers an implementation of merely a hardware circuit or processor (or multiple processors) or portion of a hardware circuit or processor and its (or their) accompanying software and / or firmware. The term circuitry also covers, for example and if applicable to the particular claim element, a baseband integrated circuit or processor integrated circuit for a mobile device or a similar integrated circuit in server, a cellular network device, or other computing or network device.

[0088] It should be appreciated by those of ordinary skill in the art that any block diagrams herein represent conceptual views of illustrative circuitry embodying the principles of the disclosure. Similarly, it will be appreciated that any flow charts, flow diagrams, state transition diagrams, pseudo code, and the like represent various processes which may be substantially represented in computer readable medium and so executed by a computer or processor, whether or not such computer or processor is explicitly shown.Atty Ref. No. A0011420WO01

[0089] Example 1. A medical method, comprising: generating a first electro- anatomical map of a treatment site, the first electro-anatomical map including tissue-fiber orientation information; determining a first pulsed field ablation (PFA) delivery configuration based on the first electro-anatomical map, the first PFA delivery configuration specifying a first set of electrodes selected from a plurality of electrodes of an ablation device and further specifying a set of parameter values for a first PFA waveform to be delivered to the treatment site via the first set of electrodes; and causing a signal generator to generate and transmit the first PFA waveform to the first set of electrodes, wherein the first PFA waveform is one of a plurality of PFA waveforms that the signal generator is configured to generate.

[0090] Example 2. The medical method of Example 1, wherein the generating includes: generating a second electro-anatomical map of the treatment site based on cardiac electrical activity data collected from the treatment site with a mapping catheter; obtaining a tissue-fiber orientation map corresponding to the treatment site; and combining the second electro-anatomical map and the tissue-fiber orientation map to generate the first electro-anatomical map of the treatment site.

[0091] Example 3. The medical method of Example 2, wherein the obtaining includes obtaining the tissue-fiber orientation map based on imaging data corresponding to the treatment site, the imaging data being selected from the group consisting of: computerized tomography scan data; magnetic resonance imaging data; ultrasound imaging data; electrogram propagation data; and intracardiac echocardiography imaging data.

[0092] Example 4. The medical method of Example 2, wherein the obtaining includes: aligning a selected set of anatomic landmarks of the second electro-anatomical map with a corresponding set of anatomic landmarks of a generic tissue-fiber orientation map corresponding to the treatment site; and applying to the generic tissue-fiber orientation map one, two, or three scaling factors corresponding to three respective spatial dimensions such that a resulting scaled tissue-fiber orientation map has the corresponding set of anatomic landmarks overlapped with the selected set of anatomic landmarks of the second electro-anatomical map.Atty Ref. No. A0011420WO01

[0093] Example 5. The medical method of Example 1, wherein the determining includes: running an optimization algorithm to determine a candidate PFA delivery configuration; and comparing a cost-function value corresponding to the candidate PFA delivery configuration with a threshold value to determine whether to use the candidate PFA delivery configuration as the first PFA delivery configuration.

[0094] Example 6. The medical method of Example 5, further comprising: when the cost-function value is greater than the threshold value, issuing an instruction to move the plurality of electrodes with respect to the treatment site.

[0095] Example 7. The medical method of Example 6, further comprising: in response to the plurality of electrodes having been moved, running the optimization algorithm to determine another candidate PFA delivery configuration.

[0096] Example 8. The medical method of Example 5, wherein the optimization algorithm is configured to evaluate a plurality of PFA delivery configurations based on respective cost-function values; and wherein any individual one of the plurality of PFA delivery configurations differs from any other one of the plurality of PFA delivery configurations in at least one of an electrode selection and a parameter value of a corresponding PFA waveform.

[0097] Example 9. The medical method of Example 5, wherein a set of inputs to the optimization algorithm includes: present positions of the plurality of electrodes at the treatment site; the first electro-anatomical map; and a planned lesion geometry.

[0098] Example 10. The medical method of Example 5, wherein the set of parameter values includes one or more of: a pulse width; a pulse amplitude; an interphase delay; an inter-pulse delay; a number of pulses; and a number of waveform segments that differ from one another in at least one waveform parameter value.

[0099] Example 11. A non-transitory computer-readable medium storing instructions that, when executed by a medical system, cause the medical system to perform operations comprising the method of Example 1.Atty Ref. No. A0011420WO01

[0100] Example 12. A medical system, comprising: an electronic controller including an electronic processor; a signal generator controlled by the electronic controller; and an ablation device including a plurality of electrodes connectable to the signal generator, wherein the electronic processor is configured to: generate a first electro- anatomical map of a treatment site, the first electro-anatomical map including tissue-fiber orientation information; and determine a first pulsed field ablation (PFA) delivery configuration based on the first electro-anatomical map, the first PFA delivery configuration specifying a first set of electrodes selected from the plurality of electrodes and further specifying a set of parameter values for a first PFA waveform to be delivered to the treatment site via the first set of electrodes; and wherein the electronic controller is configured to cause the signal generator to generate and transmit the first PFA waveform to the first set of electrodes.

[0101] Example 13. The medical system of Example 12, further comprising a mapping and navigation system coupled to the electronic controller and including a mapping catheter, wherein the electronic processor is further configured to: generate a second electro-anatomical map of the treatment site based on cardiac electrical activity data collected from the treatment site with the mapping catheter; obtain a tissue-fiber orientation map corresponding to the treatment site; and combine the second electro- anatomical map and the tissue-fiber orientation map to generate the first electro- anatomical map of the treatment site.

[0102] Example 14. The medical system of Example 13, wherein the electronic processor is further configured to obtain the tissue-fiber orientation map based on imaging data corresponding to the treatment site, the imaging data being selected from the group consisting of: computerized tomography scan data; magnetic resonance imaging data; ultrasound imaging data; electrogram propagation data; and intracardiac echocardiography imaging data.

[0103] Example 15. The medical system of Example 13, wherein the electronic processor is further configured to: align a selected set of anatomic landmarks of the second electro-anatomical map with a corresponding set of anatomic landmarks of a generic tissue-fiber orientation map corresponding to the treatment site; and apply to the genericAtty Ref. No. A0011420WO01 tissue-fiber orientation map one, two, or three scaling factors corresponding to three respective spatial dimensions such that a resulting scaled tissue-fiber orientation map has the corresponding set of anatomic landmarks overlapped with the selected set of anatomic landmarks of the second electro-anatomical map.

[0104] Example 16. The medical system of Example 12, wherein the electronic processor is further configured to: run an optimization algorithm to determine a candidate PFA delivery configuration; and compare a cost-function value corresponding to the candidate PFA delivery configuration with a threshold value to determine whether to use the candidate PFA delivery configuration as the first PFA delivery configuration.

[0105] Example 17. The medical system of Example 16, wherein the electronic controller is further configured to issue an instruction to move the plurality of electrodes with respect to the treatment site when the cost-function value is greater than the threshold value.

[0106] Example 18. The medical system of Example 17, wherein the electronic processor is further configured to run the optimization algorithm to determine another candidate PFA delivery configuration in response to the plurality of electrodes having been moved.

[0107] Example 19. The medical system of Example 16, wherein the optimization algorithm is configured to evaluate a plurality of PFA delivery configurations based on respective cost-function values; and wherein any individual one of the plurality of PFA delivery configurations differs from any other one of the plurality of PFA delivery configurations in at least one of an electrode selection and a parameter value of a corresponding PFA waveform.

[0108] Example 20. The medical system of Example 16, wherein a set of inputs to the optimization algorithm includes: present positions of the plurality of electrodes at the treatment site; the first electro-anatomical map; and a planned lesion geometry.

[0109] Example 21. The medical system of Example 16, wherein the set of parameter values includes one or more of: a pulse width; a pulse amplitude; an interphaseAtty Ref. No. A0011420WO01 delay; an inter-pulse delay; a number of pulses; and a number of waveform segments that differ from one another in at least one waveform parameter value.

Claims

Atty Ref. No. A0011420WO01 WHAT IS CLAIMED:

1. A medical method, comprising: generating (702, 704, 706) a first electro-anatomical map of a treatment site, the first electro-anatomical map including tissue-fiber orientation information; determining (710) a first pulsed field ablation (PFA) delivery configuration based on the first electro-anatomical map, the first PFA delivery configuration specifying a first set of electrodes selected from a plurality of electrodes of an ablation device and further specifying a set of parameter values for a first PFA waveform to be delivered to the treatment site via the first set of electrodes; and causing (714) a signal generator to generate and transmit the first PFA waveform to the first set of electrodes, wherein the first PFA waveform is one of a plurality of PFA waveforms that the signal generator is configured to generate.

2. The medical method of claim 1, wherein the generating includes: generating (702) a second electro-anatomical map of the treatment site based on cardiac electrical activity data collected from the treatment site with a mapping catheter; obtaining (704) a tissue-fiber orientation map corresponding to the treatment site; and combining (706) the second electro-anatomical map and the tissue-fiber orientation map to generate the first electro-anatomical map of the treatment site.

3. The medical method of claim 2, wherein the obtaining includes obtaining the tissue-fiber orientation map based on imaging data corresponding to the treatment site, the imaging data being selected from the group consisting of: computerized tomography scan data; magnetic resonance imaging data; ultrasound imaging data; electrogram propagation data; and intracardiac echocardiography imaging data.

4. The medical method of claim 2, wherein the obtaining includes:Atty Ref. No. A0011420WO01 aligning a selected set of anatomic landmarks of the second electro-anatomical map with a corresponding set of anatomic landmarks of a generic tissue-fiber orientation map corresponding to the treatment site; and applying to the generic tissue-fiber orientation map one, two, or three scaling factors corresponding to three respective spatial dimensions such that a resulting scaled tissue-fiber orientation map has the corresponding set of anatomic landmarks overlapped with the selected set of anatomic landmarks of the second electro-anatomical map.

5. The medical method of claim 1, wherein the determining includes: running an optimization algorithm to determine a candidate PFA delivery configuration; and comparing (712) a cost-function value corresponding to the candidate PFA delivery configuration with a threshold value to determine whether to use the candidate PFA delivery configuration as the first PFA delivery configuration.

6. The medical method of claim 5, further comprising: when the cost-function value is greater than the threshold value, issuing an instruction to move the plurality of electrodes with respect to the treatment site.

7. The medical method of claim 6, further comprising: in response to the plurality of electrodes having been moved (708), running (710) the optimization algorithm to determine another candidate PFA delivery configuration.

8. The medical method of claim 5, wherein the optimization algorithm is configured to evaluate a plurality of PFA delivery configurations based on respective cost-function values; and wherein any individual one of the plurality of PFA delivery configurations differs from any other one of the plurality of PFA delivery configurations in at least one of an electrode selection and a parameter value of a corresponding PFA waveform.

9. The medical method of claim 5, wherein a set of inputs to the optimization algorithm includes:Atty Ref. No. A0011420WO01 present positions of the plurality of electrodes at the treatment site; the first electro-anatomical map; and a planned lesion geometry.

10. The medical method of claim 5, wherein the set of parameter values includes one or more of: a pulse width; a pulse amplitude; an interphase delay; an inter-pulse delay; a number of pulses; and a number of waveform segments that differ from one another in at least one waveform parameter value.

11. A medical system, comprising: an electronic controller (123) including an electronic processor (124); a signal generator (122) controlled by the electronic controller; and an ablation device (110) including a plurality of electrodes (112) connectable to the signal generator, wherein the electronic processor is configured to: generate (702, 704, 706) a first electro-anatomical map of a treatment site, the first electro-anatomical map including tissue-fiber orientation information; and determine (710) a first pulsed field ablation (PFA) delivery configuration based on the first electro-anatomical map, the first PFA delivery configuration specifying a first set of electrodes selected from the plurality of electrodes and further specifying a set of parameter values for a first PFA waveform to be delivered to the treatment site via the first set of electrodes; and wherein the electronic controller is configured to cause (714) the signal generator to generate and transmit the first PFA waveform to the first set of electrodes.

12. The medical system of claim 11, further comprising a mapping and navigation system (140) coupled to the electronic controller and including a mapping catheter (146),Atty Ref. No. A0011420WO01 wherein the electronic processor is further configured to: generate (702) a second electro-anatomical map of the treatment site based on cardiac electrical activity data collected from the treatment site with the mapping catheter; obtain (704) a tissue-fiber orientation map corresponding to the treatment site; and combine (706) the second electro-anatomical map and the tissue-fiber orientation map to generate the first electro-anatomical map of the treatment site.

13. The medical system of claim 12, wherein the electronic processor is further configured to obtain the tissue-fiber orientation map based on imaging data corresponding to the treatment site, the imaging data being selected from the group consisting of: computerized tomography scan data; magnetic resonance imaging data; ultrasound imaging data; electrogram propagation data; and intracardiac echocardiography imaging data.

14. The medical system of claim 12, wherein the electronic processor is further configured to: align a selected set of anatomic landmarks of the second electro-anatomical map with a corresponding set of anatomic landmarks of a generic tissue-fiber orientation map corresponding to the treatment site; and apply to the generic tissue-fiber orientation map one, two, or three scaling factors corresponding to three respective spatial dimensions such that a resulting scaled tissue- fiber orientation map has the corresponding set of anatomic landmarks overlapped with the selected set of anatomic landmarks of the second electro-anatomical map.

15. The medical system of claim 11, wherein the electronic processor is further configured to: run (710) an optimization algorithm to determine a candidate PFA delivery configuration;Atty Ref. No. A0011420WO01 compare (712) a cost-function value corresponding to the candidate PFA delivery configuration with a threshold value to determine whether to use the candidate PFA delivery configuration as the first PFA delivery configuration; issue (714) an instruction to move the plurality of electrodes with respect to the treatment site when the cost-function value is greater than the threshold value; and run (710) the optimization algorithm to determine another candidate PFA delivery configuration in response to the plurality of electrodes having been moved (708).

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