EP4651814A1 - Dynamic waveform and vectoring adjustments for ablation therapy - Google Patents

Abstract

Methods and apparatus for performing medical ablation procedures. In an example, an electronic controller connected to an ablation waveform generator operates to iteratively adjust a plurality of waveform parameters, in response to signals from medical monitoring equipment connected to a patient, to reduce, to a safe level, an adverse reaction of the patient to the applied waveform. The iterative adjustment is performed based on calibration datasets representing lower-dimensional slices of a multidimensional space corresponding to the waveform-parameter space. In some examples, the adjustable waveform parameters include vectoring modality (e.g., monophasic or biphasic), a pulse amplitude, a pulse width, an interphase delay, an inter-pulse delay, and number of pulses in a pulse sequence.

Description

DYNAMIC WAVEFORM AND VECTORING ADJUSTMENTS FOR ABLATION

THERAPY

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63/480,775, filed January 20, 2023, the entire content of which is incorporated herein by reference.

FIELD

[0002] This application relates generally to methods and systems associated with ablation catheters, ablation generators, and other medical devices and components used in various ablation procedures.

BACKGROUND

[0003] Cardiac arrhythmias disrupt normal heart rhythm and reduce cardiac efficiency. Ablation is a procedure used to treat cardiac arrhythmias. Some ablation procedures use heat or cold energy to create fibrosis or tiny scars in the heart to block irregular electrical signals to help the heart maintain a normal heart rhythm. The delivery of some types of ablation therapy involves the use of a reliable, powerful, and precisely controlled source of electrical energy, e.g., in the form of a high-voltage pulse generator or a radio-frequency (RF) generator. Electrical pulses or continuous wave (CW) sinusoids are delivered to the intended endocardial sites to perform reversible or irreversible electroporation in the case of pulsed field ablation (PFA), and thermally induced necrosis via RF using an ablationtherapy delivery device. Reversible electroporation is typically used to reverse permeabilize cells to catalyze acceptance of genes or drugs, whereas irreversible electroporation is typically used to create permanent and lethal nanopores which can electrically isolate target areas of the myocardium and prevent arrhythmias, such as atrial fibrillation. The use of RF energy creates lesions via thermal necrosis, which can isolate target areas of the myocardium.

SUMMARY

[0004] Disclosed herein are, among other things, various aspects, features, and embodiments of methods and apparatus for performing various ablation procedures. In one example, an electronic controller connected to an ablation waveform generator operates to iteratively adjust a plurality of waveform parameters, in response to signals from medical monitoring equipment connected to a patient, to reduce, to a safe level, an adverse reaction of the patient to the applied waveform. The iterative adjustment is performed based on calibration datasets representing lower-dimensional slices of a multidimensional space corresponding to the waveform-parameter space. In some examples, the adjustable waveform parameters include vectoring modality (e.g., monophasic or biphasic), a pulse amplitude, a pulse width, an interphase delay, an interpulse delay, and number of pulses in a pulse sequence.

[0005] One example provides a medical-treatment apparatus, comprising an ablation waveform generator configured to apply electrical waveforms to a treatment element placeable in proximity to a treatment site of a patient and an electronic controller configured to control the ablation waveform generator and having an interface for receiving monitoring signals from medical monitoring equipment connected to the patient. The electronic controller is further configured to: cause the ablation waveform generator to apply a test waveform to the treatment element; process the monitoring signals to evaluate an adverse reaction of the patient to the test waveform; and change a plurality of parameters of the test waveform to reduce the adverse reaction, the plurality of parameters being selected from the parameter group consisting of vectoring modality, a pulse amplitude, a pulse width, an interphase delay, and an inter-pulse delay.

[0006] Another example provides a medical-treatment method, comprising: providing an ablation waveform generator configured to apply electrical waveforms to a treatment element placeable in proximity to a treatment site of a patient; and configuring an electronic controller to: cause the ablation waveform generator to apply a test waveform to the treatment element; process monitoring signals received from medical monitoring equipment connected to the patient to evaluate an adverse reaction of the patient to the test waveform; and change a plurality of parameters of the test waveform to reduce the adverse reaction, the plurality of parameters being selected from the parameter group consisting of vectoring modality, a pulse amplitude, a pulse width, an interphase delay, and an interpulse delay. BRIEF DESCRIPTION OF THE DRAWINGS

[0007] FIGS. 1A-1B are block diagrams illustrating a medical system according to various examples.

[0008] FIGS. 2A-2B graphically illustrate electrical pulses that can be delivered to a treatment site using the medical system of FIGS. 1A-1B according to various examples.

[0009] FIG. 3 graphically illustrates an electrical waveform that can be delivered to a treatment site using the medical system of FIGS. 1A-1B according to various examples.

[0010] FIGS. 4-7 show graphs illustrating calibration datasets that can be used to configure the medical system of FIGS. 1A-1B according to various examples.

[0011] FIG. 8 is a flowchart illustrating a configuration method that can be used to operate the medical system of FIGS. 1A-1B according to various examples.

DETAILED DESCRIPTION

[0012] Neuromuscular stimulation is a clinical adverse event of PFA. For example, pulsed fields can excite certain tissues including nerves and smooth and striated (e.g., skeletal) muscles. Clinical sequalae from stimulation of one or more skeletal muscles include patient discomfort and involuntary movement, which may disadvantageously lead to the use of deeper sedation. Some pulsed fields can also directly stimulate pain fibers (e.g., A-delta and/or C- fibers) leading to the corresponding pain/discomfort. Stimulation of vagal structures can result in bradycardia and cough reflex. The vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. The vagus is the longest nerve of the autonomic nervous system in the human body and comprises both sensory and motor fibers. In addition, stimulation of smooth muscle cells and/or autonomic nerve innervating vessels can lead to vasoconstriction and possibly vasospasms.

[0013] Electric fields generated using either current-controlled or voltage-controlled PFA generators can be vectored, e.g., to be unipolar or bipolar. Unipolar vectoring typically results in more neuromuscular stimulation than bipolar vectoring. The ablation waveform can be selected, modified, and/or adjusted such that stimulation is reduced (e.g., minimized) while an intended therapeutic purpose is still achieved.

[0014] When a PFA catheter is in an area of increased risk for stimulatory effects, some examples disclosed herein provide procedures according to which a test waveform (not causing irreversible electroporation) is applied to determine whether an unwanted clinical effect occurs. In various examples, the test waveform is designed, configured, and/or selected based on the specific sensitive structure, such as a coronary artery, that is in the vicinity of the inserted energy-delivery structure (e.g., the corresponding catheter part). In various examples, the type(s) of measured response(s) depend(s) on the type of the sensitive structure, for example, heart rate for vagal stimulation, or ST segments for coronary stimulation. In various examples, a test waveform has some characteristics of the candidate treatment waveform, such as the number of pulses, pulse frequency, interpulse delays, pulse width, etc. One or more different test waveforms are typically delivered to identify one or more candidate waveforms and then select a treatment waveform from the identified candidate waveforms.

[0015] As used herein, the term “ST segment” refers to a portion of the electrocardiogram (often abbreviated as ECG or EKG) that represents the interval between ventricular depolarization and repolarization. An ST segment abnormality (e.g., elevation or depression) may be caused by myocardial ischemia or infarction. The QRS complex is a combination of the Q wave, R wave and S wave that represent ventricular depolarization and is usually the tallest, most- visible aspect of the ECG trace. The ST segment directly follows the QRS complex. Importance of the ST segment is that it can provide important clues to physicians about potentially serious conditions, e.g., an impending heart attack.

[0016] In various examples, when the patient’s response to a test waveform indicates an unacceptable adverse reaction, the practitioner proceeds to: (i) change vectoring, e.g., from unipolar to bipolar, and/or (ii) adjust the waveform, e.g., to lower interphase and/or interpulse delays, and increase pulse frequencies to correspond to the nanosecond or low microsecond range. When a procedure does require ablation in areas of relatively intense stimulatory effects, for example, near the ventricles with concerns for stimulating the coronaries, ablation energy is applied with bipolar vectoring and a waveform is selected to cause an acceptable level of stimulatory effects. Various nonlimiting examples described herein below provide further details of these features. Some embodiments may benefit from certain features, aspects, and details disclosed in U.S. Patent Application Publication No. 2019/0038171.

[0017] FIGS. 1A-1B are block diagrams illustrating a medical system 100 according to various examples. More specifically, FIG. 1A is a block diagram illustrating an overall view of the system 100. FIG. IB is a block diagram illustrating an electronic controller used in the system 100.

[0018] In a representative example, the system 100 includes a medical device 112 and the electronic controller 114 in communication with the medical device 112. In operation, the medical device 112 is used to deliver energy (for example, PFA or electroporation energy) for treating or ablating an area of target tissue. In various examples, the medical device 112 is also used to deliver one or more test pulses or waveforms to evaluate a potential for an adverse reaction caused by the delivery of such energy.

[0019] In the example shown, the medical device 112 includes a catheter 102, a magnified view of a portion 101 of which is shown in FIG. 1A. The catheter 102 has electrodes 118 for therapeutic interaction with the selected treatment site in or on the patient’s body. In operation, the electrodes 118 deliver energy, for example, PFA energy, electroporation energy, test pulses and waveforms, and/or other transferred energy, to the treatment site. The catheter 102 includes an elongated body 120 passable through the patient’s vasculature to enable placement of the electrodes 118 in proximity to the treatment site of a patient for diagnosis and/or treatment. The elongated body 120 has a proximal portion 122 and a distal portion 124 and typically includes one or more lumens that provide mechanical, electrical, and/or fluid communication between the proximal portion 122 and the distal portion 124. In some examples, the elongated body 120 has a central or guidewire lumen 130 hosting a shaft 132 and a carrier arm 128. The shaft 132 is longitudinally movable within and with respect to the guidewire lumen 130. In operation, longitudinal movement of the shaft 132 is used to cause the carrier arm 128 to transition between the first (e.g., substantially linear) configuration and a second (e.g., looped) configuration. As an illustration, FIG. 1A shows the carrier arm 128 in the looped configuration.

[0020] The medical device 112 also includes a handle 140 connected to the proximal portion 122 of the elongated body 120. In various examples, the handle 140 includes circuitry and structures for properly operating and manipulating the catheter 102. Additionally, the handle 140 typically includes one or more connectors 104 for electrically connecting the circuitry to the electronic controller 114, e.g., to establish electrical paths between various pertinent parts of the medical device 112 and pertinent components or parts of the electronic controller 114. The handle 140 also typically has one or more actuation or control features that enable the corresponding practitioner to control, deflect, steer, or otherwise manipulate the distal portion 124 via the proximal portion 122.

[0021] In some examples, the system 100 also includes a navigation system 142 used for guiding a medical treatment procedure. In the example shown, the medical device 112 is coupled to the electronic controller 114 through the navigation system 142. In some other examples, both the medical device 112 and the navigation system 142 are directly coupled to the electronic controller 114. The navigation system 142 is designed to help visualize the real-time position and orientation of the catheter 102 within the patient’s body to increase the accuracy of targeted ablation and reacquisition of pacing sites for re-ablation. In a typical example, the navigation system 142 calculates the position and orientation of a catheter tip 108 using three magnetic sources 152, 154, 156 as references. The navigation system 142 typically relies on static magnetic fields that are calibrated and can be computer controlled. Due to the nature of magnetic fields, the orientation of the carrier arm 128 can be calculated even when the tip 108 is stationary. By calculating the strength and orientation of the magnetic fields at a given location, the Cartesian coordinates (x, y, z) of the tip 108 are typically calculated together with the roll, pitch, and yaw angles of the carrier arm 128.

[0022] In various examples, the electronic controller 114 includes components and circuits for the delivery of one or more energy modalities to the electrodes 118. In the example shown in FIG. IB, the electronic controller 114 includes an ablation waveform generator 144, control circuitry 146, and input/output (BO) devices 160. The control circuitry 146 includes a processing circuit (e.g., a general-purpose processor) 148 and a memory 150. The I/O devices 160 of the electronic controller 114 typically provide multiple I/O channels, e.g., including one or more channels 162 for communicating with the external monitoring devices, and at least one I/O channel 164 for operatively connecting the waveform generator 144 to the medical device 112 (also see FIG. 1A). The electronic controller 114 is operable in a plurality of operating modes, which can be selected for specific medical procedures as needed or appropriate.

[0023] In various examples, the memory 150 has buffers to temporarily store received data and nonvolatile data- storage devices to more permanently store data and program code. In operation, the memory 150 provides pertinent data and program code to the processing circuit 148. The program code, when executed by the processing circuit 148 enables the electronic controller 114 to perform signal processing and generate various control and communication signals. In some examples, the processing circuit 148 performs rendering processing of input signals received from the external monitoring devices and outputs, through the VO devices 160, the corresponding viewable images, charts, and/or graphs for being viewed on an external display.

[0024] In various examples, the medical monitoring devices include one or more devices from the following group of devices: a diaphragmatic or thoracic excursion assessment device; an accelerometer; an electromyography (EMG) machine; an ECG recorder; a vital signs monitor; an airway pressure monitor; and an expiratory carbon-dioxide monitor. In other examples, other suitable patient monitoring devices are similarly used and linked to the electronic controller 114 through the VO devices 160. In some examples, the VO devices 160 include at least one VO interface device for supporting a wireless data link.

[0025] In some examples, the electronic controller 114 is also connected, via the VO devices 160, to an operator interface device 170. In various examples, the operator interface device 170 includes: a touch screen; buttons, knobs, and/or keys; light indicators (e.g., colored light emitting diodes, LEDs); a speaker; a switch; a joystick; and other control accessories connected and configured to enable the operator to properly operate the electronic controller 114 and the medical device 112. The operator interface device 170 also typically enables the operator to see thereon at least some indicators generated by the electronic controller 114 in response to the signals received via the I/O devices 160 from the medical monitoring devices.

[0026] FIGS. 2A-2B graphically illustrate electrical pulses that can be delivered to the treatment site using the system 100 according to various examples. More specifically, FIG. 2A graphically illustrates a monophasic (unipolar) pulse 210. The monophasic pulse 210 has an amplitude Vo and a pulse width T_p. Both the amplitude Vo and the pulse width T_p are selectable and controllable via the waveform generator 144. FIG. 2B graphically illustrates a biphasic (bipolar) pulse 220. The biphasic pulse 220 includes a positive pulse 222 and a negative pulse 224. Both the positive pulse 222 and the negative pulse 224 have the amplitude aVo and the pulse width T_p, where a is the scaling factor, e.g., in the range between 0.1 and 10. The time delay between the positive pulse 222 and the negative pulse 224 is di. The parameter di is hereafter referred to as the interphase delay. The parameters a and di of the biphasic pulse 220 are also selectable and controllable via the waveform generator 144.

[0027] FIG. 3 graphically illustrates an electrical waveform 300 that can be delivered to the treatment site using the system 100 according to various examples. The electrical waveform 300 comprises a sequence of N biphasic pulses 220, which are labeled 220i, 2202, ..., 220N, respectively. The time delay between two consecutive biphasic pulses 220 in the waveform 300 is d2. The parameter d2 is hereafter referred to as the inter-pulse delay. The total duration of the waveform 300 is T_w. In various examples, the time T_w is in the range between 0.1 ms and 10 ms. The parameters N, d2, and T_w of the waveform 300 are selectable and controllable via the waveform generator 144.

[0028] The pulse/waveform parameters described above in reference to FIGS. 2-3 represent an example multidimensional parameter space within which a specific set of parameter values is selected to deliver safe and effective ablation therapy to a specific treatment site of a specific patient. In various examples, such selection is made based on calibration datasets and further using a system configuration method 800. Nonlimiting examples of such calibration datasets are described in more detail below in reference to FIGS. 4-7. The system configuration method 800 is described in more detail below in reference to FIG. 8. [0029] FIGS. 4-7 show graphs illustrating calibration datasets that can be used to configure system 100 according to various examples. In a typical example, such calibration datasets are obtained using one or more clinical trials carried out using a relatively large set of different energy-delivery protocols. The protocols are constructed using design-of-experiments (DOE) approaches. Herein, the term “design of experiments” refers to a branch of applied statistics that deals with planning, conducting, analyzing, and interpreting controlled tests to evaluate the factors that control the value of a parameter or a group of parameters, e.g., as applied to the above-mentioned parameter space of the system 100.

[0030] FIG. 4 is contour plot showing the amplitude of involuntary movement (AIM) as a function of the interphase delay di and the inter-pulse delay d2. This example set of calibration data was obtained by measuring muscle contraction initiated by electrical stimulation of the tibialis anterior muscle on the right leg. The corresponding AIM is represented by the leg-deflection angle in degrees.

[0031] FIG. 5 is contour plot showing VAS values as a function of the average applied current and the inter-pulse delay d2. Herein, the acronym VAS represents the Visual Analogue Scale, which is a pain rating scale often used in epidemiologic and clinical research to measure the intensity or frequency of various symptoms. For example, the amount of pain that a patient feels ranges across a continuum from no pain to an extreme amount of pain. From the patient’s perspective, the spectrum of pain appears continuous, i.e., does not typically take discrete jumps, as discrete pain-categorization scales might suggest. Unlike the latter, VAS values enable continuous sampling of the pain spectrum. The set of calibration data shown in FIG. 5 was obtained by querying patients subjected to the sequence 300.

[0032] FIG. 6 is contour plot showing PRI values as a function of the amplitude a Vo and the interphase delay di. Herein, the acronym PRI represents the Pain Rating Index obtained using a McGill Pain Questionnaire (MPQ). The MPQ includes three major measures: the PRI, the number of words chosen to describe pain, and the present pain intensity. The PRI is built by numerical grading of the words describing sensory, affective, and evaluative aspects of pain. [0033] FIG. 7 is contour plot showing total pain-index (PI) values as a function of the amplitude aVo and the interphase delay di. Herein, each of the total PI values is computed by taking a sum of the corresponding PRI value (also see FIG. 6) and the corresponding VAS value for the same vector value (aVo, di). The set of calibration data shown in FIG. 7 was obtained by querying patients subjected to the sequence 300.

[0034] In various examples, the calibration data used to configure the system 100 include a plurality of datasets representing slices of the above-mentioned multidimensional operating-parameter space of the system 100. In a representative example, various dimensions of such multidimensional operating-parameter space include: the vectoring modality (e.g., monophasic or biphasic, FIGS. 2-3); the number of pulses in the pulse sequence 300 (e.g., N, FIG. 3); the pulse amplitude Vo; the scaling factor a; the pulse width T_p; the interphase delay di; and the inter-pulse delay d2 (also see FIGS. 2-3). The calibration data are processed using suitable DOE analyses to construct a corresponding cost function for the optimization module of the electronic controller 114 to use in the method 800. In a representative example, such DOE analyses include some or all of the following blocks:

(i) Examination of the calibration data for outliers, inconsistencies, and experiment errors.

(ii) Construction of a plurality of graphs representing lower-dimensional slices of the multidimensional operating-parameter space. Such graphs may include but are not limited to (a) response distributions, such as histograms, box plots, and the like; (b) responses versus time order scatter plots to check for possible time effects; (c) responses versus factor levels plots; (d) main effects mean plots; (e) normal or half-normal plots of the effects; (f) interaction plots; and (g) other suitable plots as applicable to system 100. At least some of the graphs may be conceptually analogous to the graphs illustrated in FIGS. 4-7.

(iii) Create a theoretical model of the responses. The clinical trials are typically designed with a particular model in mind to enable sufficient sampling of the corresponding multidimensional parameter space. In various examples, the theoretical model is an analytical model, a numerical model, or a combination of analytical and numerical sub-models. (iv) Refine the model using stepwise regression methods and/or parameter-value significance information and by fitting the calibration data with the model.

(v) Based on the plurality of graphs, identify an optimal subspace of the multidimensional operating-parameter space corresponding to “optimal” settings of the system 100 for the ablation-therapy procedure in question.

(vi) Based on the refined model, construct a cost function causing the optimization module of the electronic controller 114 to converge toward the optimal subspace in response to a set of inputs from the pertinent set of medical monitoring devices connectable to the system 100 via the I/O devices 160.

In some cases, the above sequence of blocks is modified to be better suitable for the type of available calibration data. Not all types of experiments can be analyzed with one set procedure, and two or more different procedures may be used in the corresponding DOE analyses in such cases. In addition, medical-engineering judgment and overall expertise of persons of ordinary skill in the pertinent art can play a role in devising specific implementations of the above-outlined DOE-analysis sequence.

[0035] FIG. 8 is a flowchart illustrating the system configuration method 800 according to various examples. In some examples, the method 800 is implemented via the electronic controller 114 in a fully automatic mode, in which no additional input from the system’s human operator is needed after the method is initiated. In some other examples, the method 800 has one or more checkpoints, wherein a human decision or prompt is solicited. In such examples, the remainder of the method 800 is still executed by the corresponding controller circuitry of the electronic controller 114 in an automated manner, e.g., by running a corresponding program code.

[0036] The method 800 includes applying a test waveform to the treatment site (in block 802). In some examples, for the first instance of the block 802, the test waveform is a sequence of n monophasic pulses 210 with an amplitude Vo = 60 V and a pulse width T_p = 100 ps, delivered with 5-kHz pulse-repetition rate. The number n is in the range between 5 and 15. For each one of the subsequent instances of the block 802, the test waveform is selected based on adjusted parameters determined in block 812, e.g., as described below. [0037] The method 800 also includes receiving (in block 804) one or more monitoring signals corresponding to a time period associated with the effects of the test waveform on the patient. The monitoring signals are typically received by the electronic controller 114 through the I/O devices 160 as described above. In different examples, different sets of monitoring signals are received, with the specific signal types in such sets depending on the composition of the monitoring equipment linked up to the system 100 through the I/O devices 160.

[0038] The method 800 also includes the electronic controller 114 automatically evaluating (in decision block 806) the received monitoring signals for manifestations of an unacceptable adverse reaction to the test waveform from the patient. In some specific examples, such manifestation includes one or more of the following: (i) elevation or depression of the ST segment in the ECG trace; (ii) bradycardia, e.g., heart rate lower than 50 bpm; (iii) prolonged pauses in the heartbeat compared to the baseline heart rate; (iii) a coughing response or a coughing-like increase of airway pressure in an intubated patient;

(iv) characteristic changes of the CO2 concentration in the exhale flow or in the airways;

(v) relatively high level of muscular stimulation; and (vi) large shifts in the impedance map or large movement of catheters, e.g., as detected using the navigation system 142. In some other specific examples, other manifestations are similarly detected, as enabled by the corresponding monitoring equipment linked up to the system 100.

[0039] When a quantifier of at least one of the adverse reactions exceeds a respective fixed threshold value (“Yes” in the decision block 806), the electronic controller 114 operates to automatically generate an alert (in block 808), e.g., intended for the attending physician. In various examples, the generated alert includes a corresponding alert banner or conspicuous message displayed on the screen of the operator interface device 170, a flashing LED light on the operator interface device 170, and/or a distinct sound emitted by the speaker of the operator interface device 170. Depending on the severity of the adverse reaction, the attending physician or other qualified individual may decide to terminate or pause the method 800 and/or to take other warranted remedial action(s). When the quantifiers of various manifestations of the adverse reaction are all below the respective fixed threshold values (“No” in the decision block 806), the electronic controller 114 operates to skip the block 808. The various fixed threshold values used to arrive at the warranted decision in the decision block 806 are the parameters of the optimization algorithm invoked by the method 800.

[0040] The method 800 also includes the electronic controller 114 computing (in decision block 810) a cost- function value based on the pertinent parameters of the test waveform used in the block 802 and further based on the monitoring signals received in the block 804. The decision block 810 also includes comparing the computed cost-function value with a respective fixed threshold value, which is yet another parameter of the optimization algorithm. When the computed cost-function value is below the respective fixed threshold value (“Yes” in the decision block 810), the electronic controller 114 operates the system 100 to deliver (in block 814) the treatment waveform corresponding to the test waveform. Otherwise (“No” in the decision block 810), the processing of the method 800 is directed to block 812.

[0041] The method 800 also includes the electronic controller 114 changing (in the block 812) one or more parameters of the test waveform. The one or more parameters being changed in the block 812 belong to the above-described multidimensional parameter space. In a representative example, adjustments to the parameter values are determined using a cost-function optimization algorithm selected from the group consisting of: an algorithm based on evaluation of Hessians, a gradient-descent algorithm, a quasi-Newton method, and a particle- swarm-optimization algorithm. Additionally, other suitable costfunction optimization algorithms can be used, depending on the specific composition of the system 100 and the linked medical monitoring devices. The adjusted parameter values are then used to configure an updated test waveform for use in the next instance of the block 802. The processing loop including the blocks 802-812 typically causes several iterative adjustments to the waveform parameters until the “Yes” criteria are satisfied in the decision block 810, at which point the electronic controller 114 configures the system 100 to deliver the corresponding treatment waveform in the block 814.

[0042] In some examples, an often-encountered change prompted by the above-described cost- function optimization algorithm in the first instance of the block 812 is the change of the vectoring modality from monophasic to biphasic. In subsequent instances of the block and the product aVo. Towards the end of the iterative adjustment (i.e., for the later instances of the block 812), finer tuning of the waveform occurs, typically via changes of the pulse width T_p, interphase delay di, and inter-pulse delay d2, the interplay of which can be relatively complex. The cost-function optimization algorithm handles such interplay in an incremental manner to move the cost-function value into the acceptable range, thereby causing the method 800 to exit the processing loop 802-812 and perform operations of the block 814.

[0043] According to one example disclosed above, e.g., in the summary section and/or in reference to any one or any combination of some or all of FIGS. 1-8, provided is a medical-treatment apparatus, comprising: an ablation waveform generator configured to apply electrical waveforms to a treatment element placeable in proximity to a treatment site of a patient; and an electronic controller configured to control the ablation waveform generator and having an interface for receiving monitoring signals from medical monitoring equipment connected to the patient, the electronic controller being further configured to: cause the ablation waveform generator to apply a test waveform to the treatment element; process the monitoring signals to evaluate an adverse reaction of the patient to the test waveform; and change a plurality of parameters of the test waveform to reduce the adverse reaction, the plurality of parameters being selected from the parameter group consisting of vectoring modality, a pulse amplitude, a pulse width, an interphase delay, and an inter-pulse delay.

[0044] In some examples of the above medic al-treatment apparatus, the electronic controller is further configured to cause the ablation waveform generator to apply a treatment waveform to the treatment element, the treatment waveform being generated based on parameter values determined based on the test waveform.

[0045] In some examples of any of the above medical-treatment apparatus, the monitoring equipment is selected from the group of devices consisting of a diaphragmatic or thoracic excursion assessment device, an accelerometer, an electromyography machine, an electrocardiogram recorder, a vital signs monitor, an airway pressure monitor, and a medical carbon-dioxide monitor. [0046] In some examples of any of the above medical-treatment apparatus, the apparatus further comprises a catheter; and wherein the catheter includes the treatment element.

[0047] In some examples of any of the above medical-treatment apparatus, the electronic controller is configured to change the plurality of parameters based on calibration datasets representing lower-dimensional slices of a higher-dimensional parameter space corresponding to the plurality of parameters.

[0048] In some examples of any of the above medical-treatment apparatus, the electronic controller is configured to change the plurality of parameters based on a cost function constructed using the calibration datasets.

[0049] In some examples of any of the above medical-treatment apparatus, the electronic controller is further configured to perform iterative minimization of the cost function.

[0050] In some examples of any of the above medical-treatment apparatus, the apparatus further comprises an operator interface device; and wherein the electronic controller is further configured to cause the operator interface device to produce an alert signal when a quantifier of the adverse reaction exceeds a threshold value.

[0051] In some examples of any of the above medical-treatment apparatus, the apparatus further comprises a navigation system to guide the treatment element to the treatment site.

[0052] In some examples of any of the above medical-treatment apparatus, the electronic controller is further configured to change a number of biphasic pulses in the test waveform.

[0053] In some examples of any of the above medical-treatment apparatus, the apparatus is configured to perform a medical procedure selected from the group of procedures consisting of pulsed field ablation, RF ablation, reversible electroporation, and irreversible electroporation.

[0054] According to another example disclosed above, e.g., in the summary section and/or in reference to any one or any combination of some or all of FIGS. 1-8, provided is a medical-treatment method, comprising: providing an ablation waveform generator configured to apply electrical waveforms to a treatment element placeable in proximity to a treatment site of a patient; and configuring an electronic controller to: cause the ablation waveform generator to apply a test waveform to the treatment element; process monitoring signals received from medical monitoring equipment connected to the patient to evaluate an adverse reaction of the patient to the test waveform; and change a plurality of parameters of the test waveform to reduce the adverse reaction, the plurality of parameters being selected from the parameter group consisting of vectoring modality, a pulse amplitude, a pulse width, an interphase delay, and an inter-pulse delay.

[0055] In some examples of the above medic al-treatment method, the electronic controller is further configured to cause the ablation waveform generator to apply a treatment waveform to the treatment element, the treatment waveform being generated based on parameter values determined based on the test waveform.

[0056] In some examples of any of the above medical-treatment methods, the monitoring equipment is selected from the group of devices consisting of a diaphragmatic or thoracic excursion assessment device, an accelerometer, an electromyography machine, an electrocardiogram recorder, a vital signs monitor, an airway pressure monitor, and a carbon-dioxide monitor.

[0057] In some examples of any of the above medical-treatment methods, the treatment element is a part of a catheter.

[0058] In some examples of any of the above medical-treatment methods, the electronic controller is configured to change the plurality of parameters based on calibration datasets representing lower-dimensional slices of a higher-dimensional parameter space corresponding to the plurality of parameters.

[0059] In some examples of any of the above medical-treatment methods, the electronic controller is configured to change the plurality of parameters based on a cost function constructed using the calibration datasets.

[0060] In some examples of any of the above medical-treatment methods, the electronic controller is further configured to perform iterative minimization of the cost function. [0061] In some examples of any of the above medical-treatment methods, the electronic controller is further configured to cause an operator interface device to produce an alert signal when a quantifier of the adverse reaction exceeds a threshold value.

[0062] In some examples of any of the above medical-treatment methods, the method further comprises performing a medical procedure selected from the group of procedures consisting of pulsed field ablation, RF ablation, reversible electroporation, and irreversible electroporation.

[0063] 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 described 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.

[0064] 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.

[0065] 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.

[0066] 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.

[0067] 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 . ’ ’

[0068] 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.

[0069] 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].”

[0070] 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.

[0071] 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.

[0072] 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, 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.

[0073] 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.

[0074] 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.

[0075] The following examples are a non-limiting list of clauses in accordance with one or more techniques of this disclosure.

[0076] Example 1. A medical-treatment apparatus, comprising: an ablation waveform generator configured to apply electrical waveforms to a treatment element placeable in proximity to a treatment site of a patient; and an electronic controller configured to control the ablation waveform generator and having an interface for receiving monitoring signals from medical monitoring equipment connected to the patient, the electronic controller being further configured to: cause the ablation waveform generator to apply a test waveform to the treatment element; process the monitoring signals to evaluate an adverse reaction of the patient to the test waveform; and change a plurality of parameters of the test waveform to reduce the adverse reaction, the plurality of parameters being selected from the parameter group consisting of vectoring modality, a pulse amplitude, a pulse width, an interphase delay, and an inter-pulse delay.

[0077] Example 2. The apparatus of Example 1, wherein the electronic controller is further configured to cause the ablation waveform generator to apply a treatment waveform to the treatment element, the treatment waveform being generated based on parameter values determined based on the test waveform.

[0078] Example 3. The apparatus of either Example 1 or Example 2, wherein the monitoring equipment is selected from the group of devices consisting of a diaphragmatic or thoracic excursion assessment device, an accelerometer, an electromyography machine, an electrocardiogram recorder, a vital signs monitor, an airway pressure monitor, and a blood pressure monitor.

[0079] Example 4. The apparatus of Example 1, further comprising a catheter; and wherein the catheter includes the treatment element.

[0080] Example 5. The apparatus of Example 1, wherein the electronic controller is configured to change the plurality of parameters based on calibration datasets representing lower-dimensional slices of a higher-dimensional parameter space corresponding to the plurality of parameters.

[0081] Example 6. The apparatus of Example 5, wherein the electronic controller is configured to change the plurality of parameters based on a cost function constructed using the calibration datasets.

[0082] Example 7. The apparatus of Example 6, wherein the electronic controller is further configured to perform iterative minimization of the cost function.

[0083] Example 8. The apparatus of any of Examples 1-7, further comprising an operator interface device; and wherein the electronic controller is further configured to cause the operator interface device to produce an alert signal when a quantifier of the adverse reaction exceeds a threshold value. [0084] Example 9. The apparatus of any of Examples 1-8, further comprising a navigation system to guide the treatment element to the treatment site.

[0085] Example 10. The apparatus of any of Examples 1-9, wherein the electronic controller is further configured to change a number of pulses in the test waveform.

[0086] Example 11. The apparatus of any of Examples 1-10, wherein the apparatus is configured to perform a medical procedure selected from the group of procedures consisting of pulsed field ablation, radio-frequency ablation, reversible electroporation, and irreversible electroporation.

[0087] Example 12. A medical-treatment method, comprising: providing an ablation waveform generator configured to apply electrical waveforms to a treatment element placeable in proximity to a treatment site of a patient; and configuring an electronic controller to: cause the ablation waveform generator to apply a test waveform to the treatment element; process monitoring signals received from medical monitoring equipment connected to the patient to evaluate an adverse reaction of the patient to the test waveform; and change a plurality of parameters of the test waveform to reduce the adverse reaction, the plurality of parameters being selected from the parameter group consisting of vectoring modality, a number of pulses, a pulse amplitude, a pulse width, a pulse shape, an interphase delay, and an inter-pulse delay.

[0088] Example 13. The method of Example 12, wherein the electronic controller is further configured to cause the ablation waveform generator to apply a treatment waveform to the treatment element, the treatment waveform being generated based on parameter values determined based on the test waveform.

[0089] Example 14. The method of either Example 12 or Example 13, wherein the monitoring equipment is selected from the group of devices consisting of a diaphragmatic or thoracic excursion assessment device, an accelerometer, an electromyography machine, an electrocardiogram recorder, a vital signs monitor, an airway pressure monitor, and a carbon-dioxide monitor. [0090] Example 15. The method of any of Examples 12-14, wherein the treatment element is a part of a catheter.

[0091] Example 16. The method of any of Examples 12-15, wherein the electronic controller is configured to change the plurality of parameters based on calibration datasets representing lower-dimensional slices of a higher-dimensional parameter space corresponding to the plurality of parameters.

[0092] Example 17. The method of Example 16, wherein the electronic controller is configured to change the plurality of parameters based on a cost function constructed using the calibration datasets.

[0093] Example 18. The method of Example 17, wherein the electronic controller is further configured to perform iterative minimization of the cost function.

[0094] Example 19. The method of any of Examples 12-18, wherein the electronic controller is further configured to cause an operator interface device to produce an alert signal when a quantifier of the adverse reaction exceeds a threshold value.

[0095] Example 20. The method of any of Examples 12-19, further comprising performing a medical procedure selected from the group of procedures consisting of pulsed field ablation, radio-frequency ablation, reversible electroporation, and irreversible electroporation.

Claims

CLAIMS What is claimed is:

1. A medical-treatment apparatus, comprising: an ablation waveform generator configured to apply electrical waveforms to a treatment element placeable in proximity to a treatment site of a patient; and an electronic controller configured to control the ablation waveform generator and having an interface for receiving monitoring signals from medical monitoring equipment connected to the patient, the electronic controller being further configured to: cause the ablation waveform generator to apply a test waveform to the treatment element; process the monitoring signals to evaluate an adverse reaction of the patient to the test waveform; and change a plurality of parameters of the test waveform to reduce the adverse reaction, the plurality of parameters being selected from the parameter group consisting of vectoring modality, a pulse amplitude, a pulse width, an interphase delay, and an inter-pulse delay.

2. The apparatus of claim 1, wherein the electronic controller is further configured to cause the ablation waveform generator to apply a treatment waveform to the treatment element, the treatment waveform being generated based on parameter values determined based on the test waveform.

3. The apparatus of claim 1, wherein the monitoring equipment is selected from the group of devices consisting of a diaphragmatic or thoracic excursion assessment device, an accelerometer, an electromyography machine, an electrocardiogram recorder, a vital signs monitor, an airway pressure monitor, and a blood pressure monitor.

4. The apparatus of claim 1, further comprising a catheter; and wherein the catheter includes the treatment element.

5. The apparatus of claim 1, wherein the electronic controller is configured to change the plurality of parameters based on calibration datasets representing lower-dimensional slices of a higher-dimensional parameter space corresponding to the plurality of parameters.

6. The apparatus of claim 5, wherein the electronic controller is configured to change the plurality of parameters based on a cost function constructed using the calibration datasets.

7. The apparatus of claim 6, wherein the electronic controller is further configured to perform iterative minimization of the cost function.

8. The apparatus of claim 1, further comprising an operator interface device; and wherein the electronic controller is further configured to cause the operator interface device to produce an alert signal when a quantifier of the adverse reaction exceeds a threshold value.

9. The apparatus of claim 1, further comprising a navigation system to guide the treatment element to the treatment site.

10. The apparatus of claim 1, wherein the electronic controller is further configured to change a number of pulses in the test waveform.

11. The apparatus of claim 1, wherein the apparatus is configured to perform a medical procedure selected from the group of procedures consisting of pulsed field ablation, radiofrequency ablation, reversible electroporation, and irreversible electroporation.