Systems and methods for ablation visualization and treatment confirmation

Abstract

Examples described herein include visualization techniques for ablation. In some examples, the ablation includes a combination of electrolysis and electroporation. Tissue within a zone of a target region is treated using endoluminal or other ablation. Imaging devices may be used to image the zone to identify treated regions within the zone by observing the treated tissue that changes color. In some examples, the imaging may be performed before, during, and after treatment. Confirmation of treatment can be obtained by observing coloration of treated tissue in images. Regions of tissue that were not treated, or were insufficiently treated, may be identified using their different coloration in contrast to treated regions. Based on a location of the treated regions, additional endoluminal ablation may be performed at selected additional regions within the zone that were missed, using either manual techniques, or partially or wholly automated techniques.

Description

SYSTEMS AND METHODS FOR ABLATION VISUALIZATION ANDTREATMENT CONFIRMATIONCROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] This application claims priority to U.S. Provisional Application No. 63 / 598,893 filed November 14, 2023, which is incorporated herein by reference, in its entirety, for any purpose.TECHNICAL FIELD

[0002] The present disclosure relates generally to the field of medical procedure visualization and treatment confirmation. Examples are described that utilize visualization of endoluminal ablation zones for planning and confirmation of tissue treatment.BACKGROUND

[0003] Ablation in soft tissue, specifically endoluminal structures, has been used for a number of clinical applications including endovascular treatment for varicose veins, gastrointestinal (GI) tract ablation for Barrett’s esophagus and insulin resistance, and lung ablation for chronic obstructive pulmonary disease as prime examples.

[0004] Regarding the small intestine, the duodenum plays a fundamental role in glucose homeostasis and metabolic disease that has been evidenced by glycemic improvement seen in patients with gastric bypass procedures. An emerging investigational procedure, duodenal mucosal resurfacing (DMR) has shown promising outcomes for patients with diabetes and fatty liver. Despite favorable outcomes in glycemic control, there are safety concerns with thermal ablation used in the duodenum and early cases of duodenal stenosis. Ablation can be achieved in the duodenum with a variety of energy modalities. Thermal ablation has come with the caveat that protection of the underlying muscle layer must occur given the potential for thermal damage to the muscle which may result in stricturing of the bowel in the tissue recovery and healing phase post-procedure. Thus, thermal ablation has been coupled with a submucosal injection to provide a buffer in order to provide this protection. Ablation using thermal-risk mitigating energy modalities such as pulsed field ablation, such as irreversible electroporation (IRE), high-frequency irreversible electroporation (H-FIRE), electroporation and electrolysis (E2), etc., can potentially avoid the need for the submucosal lift given that depth of ablation can be modeled and controlled to apply trans-mucosal ablation in the duodenum to treat duodenopathy that directly contributes to the patient’s insulin resistance.

[0005] Regarding the lung, the lining of the lung plays a fundamental role in the overall lung function. Goblet cells which are present in the endobronchial lining of the lung secrete mucin and create a protective mucous layer which helps trap microorganisms. In chronic bronchitis (CB), a chronic obstructive pulmonary disease (COPD), inflammation within the airway wall leads to mucous hypersecretion from an overabundance of goblet cells. Energy modalities including both thermal (thermal vapor ablation) and thermal-mitigating modalities such as pulsed ablation, such as IRE and H-FIRE, can potentially be applied to ablate the endobronchial lining of the lung in order to reduce the number of goblet cells thus reducing mucous secretion and improving pulmonary function in the process.

[0006] While thermal-mitigating energy modalities hold promise for ablation the small intestine and lung, the treatments have not been fully optimized. A known shortcoming of specifically using IRE parameters for mucosal ablation in the small intestine and lungs is the inability to visualize where treatment has been applied due to the reliance on IRE as the treatment modality. This has led to initial experience being frustrating for medical practitioners without knowing a treated region of tissue that has been ablated, an extent of treatment, potential gaps or skips in treatment, and a degree of treatment to determine overablating or under-ablating in the treated region.SUMMARY

[0007] Examples of methods are described herein. An example method may include treating tissue within a zone of a targeted region using ablation from an ablation device, the ablation comprising applying electroporation energy, imaging the zone to identify treated regions within the zone, and performing additional ablation by the ablation device at selected additional regions within the zone based on a location of the treated regions.

[0008] Some example methods further include delivering medication to the zone based on an appearance of the treated regions.

[0009] In some example methods, the ablation includes a combination of electroporation and electrolysis. Some example methods further include using white light endoscopy to image the zone, and wherein the treated regions have a different visual appearance than nontreated regions. In some example methods, the treated regions appear discolored (e.g., white). Some example methods further include determining a degree of the ablation at the treated regions by image recognition or visual evaluation, and adjusting the additional ablation at the selected additional regions based on the degree of the ablation at the treated regions. In some examplemethods, said adjusting the additional ablation includes controlling at least one of pulse duration, a current applied, a charge applied, a voltage applied, a number of pulses or a combination thereof.

[0010] Some example methods further include, prior to treating the tissue, marking at least one of a leading edge or a trailing edge of the zone using the ablation device to mark the tissue. In some example methods, said marking the zone includes applying energy to the zone. In some example methods, said marking the zone includes applying a combination of electroporation and electrolysis. In some example methods, said marking includes applying a first amount of energy to the zone, and wherein said treating includes applying a second amount of energy to the zone, wherein the first amount is less than the second amount.

[0011] Some example methods further include tagging portions of images generated by said imaging to tag the selected additional regions. Some example methods further include comparing said tagging with kinematic data from a robotic system used to perform the ablation, and generating position data for the selected additional regions based on said comparing. In some example methods, said performing additional ablation includes using the position data to position the robotic system to treat the selected additional regions.

[0012] Examples of methods are described herein. An example method may include treating tissue within a zone of a target region using ablation including a combination of electroporation and electrolysis, imaging the zone, and identifying treated regions within the zone based on the imaging.

[0013] In some example methods, said imaging uses white light endoscopy, narrow band imaging (NBI), fluorescence, chromoendoscopy, or a combination thereof. In some example methods, said identifying includes determining whether the treated regions are different from at least one untreated region in appearance using image recognition, kinematic, shape sensing and / or visual evaluation. Some example methods further include determining a degree of ablation at the treated regions by image recognition or visual evaluation.

[0014] In some example methods, treating the tissue is performed with an ablation device and prior to treating the tissue, marking at least one of a leading edge or a trailing edge of the zone using the ablation device to mark the tissue. Some example methods further include comparing the leading edge, trailing edge, and / or overlapping edges with at least one of shape sensing data, kinematic data, or positional data, and positioning the ablation device between the leading and trailing edges based on the at least one of shape sensing data, kinematic data, or positional data to perform the ablation. Some example methods further include markingthe trailing edge, moving an imaging device to the trailing edge, identifying either a landmark or an electrolysis marker in the zone to identify the leading edge, moving the imaging device to a proximal portion of the treatment zone to measure a travel distance from the trailing edge to either the landmark or the electrolysis marker, moving the imaging device to the leading edge, pre-plotting a map including the zone, planning one or more treatment segments in the map based on a predetermined length in the treatment zone, a treatment location, the travel distance or combinations thereof, and moving the ablation device to the one or more planned treatment segments. In some example methods, said pre-plotting a map includes anatomical positioning. Some example methods further include dynamically adjusting one or more locations of the one or more treatment segments to update the planned one or more treatment segments.

[0015] Examples of systems are described herein. An example system includes an ablation device including a plurality of electrodes that contacts tissue, and performing ablation of the contacted tissue where the ablation includes applying electroporation energy, an imaging device in proximity to the ablation device that images a zone of a target region, and a controller coupled to the ablation device and the imaging device, the controller controls the ablation device to mark tissue within the zone using ablation by controlling a charge applied to the plurality of electrodes, and controls the imaging device to image the zone to visualize the marked regions. In some example systems, the ablation includes a combination of electroporation and electrolysis. In some example systems, controlling the ablation device to mark tissue includes applying energy comprising a combination of electroporation and electrolysis. In some example systems, visualizing the marked regions includes using white light endoscopy to image the zone, and the marked regions have a different visual appearance than non-marked regions.

[0016] Some example systems further include an elongate flexible device. In some example systems, the plurality of electrodes includes at least one electrode inserted through a working channel of the elongate flexible device. In some example systems, at least one expandable member at a distal portion of the elongate flexible device.

[0017] In some example systems, the imaging device includes an ultrasound imaging sensor and light source. In some example systems, the imaging device performs white light endoscopy, NBI, fluorescence, or a combination thereof.

[0018] Some example systems further include an elongate flexible device including the imaging device, wherein the plurality of electrodes are distally attached to the elongate flexible device.

[0019] Some example systems further include a processor that receives data from the imaging device and performs image recognition to identify the marked regions. In some example systems, the processor further determines a degree of ablation at the marked regions based on the data from the imaging device, and the controller further controls charge, by selecting a duration, a voltage or range of voltages, a plurality of pulses, or combinations thereof, to be applied on the marked regions based on the degree of ablation. Some example systems further include a robotic system that robotically actuates the ablation device and the imaging device, wherein the processor further determines the region within the zone, and wherein the controller causes the robotic system to position the ablation device and the imaging device at the region within the zone. In some example systems, the controller further tags portions of one or more images generated by the imaging device to compare the tagged portions of the one or more images with at least one of shape sensing data, kinematic data, or positional data, and the controller positions the ablation device in proximity to the region within the zone based on the at least one of shape sensing data, kinematic data, or positional data.

[0020] Some example systems further include a display that displays one or more images generated by the imaging device, and the controller is further allows a user visual evaluation to determine a degree of ablation at the marked regions. In some example systems, the controller further allows a user to control at least one of a duration, a voltage or a number of pulses to be applied for performing additional ablation to the treated regions, or a position of the ablation device and the imaging device to be at the region within the zone based on the marked regions.

[0021] Examples of non-transitory computer-readable storage media are described herein, which may be encoded with instructions that when executed by a controller, cause the controller to control an ablation device to treat tissue within a zone of a target region using ablation by controlling a charge applied to a plurality of electrodes of the ablation device where the ablation including applying electroporation energy, control an imaging device to image the zone to generate one or more images, and control the ablation device to perform additional ablation at selected additional regions within the zone based on a location of the treated regions determined based on the one or more images.

[0022] Examples of methods are described herein. An example method includes positioning an electrolytic device proximate a tissue region, and performing electrolysis to discolor the tissue region and provide a visual marker.

[0023] Example methods may further include delivering energy for treatment based on a location of the visual marker. In some example methods, performing electrolysis on the tissue comprises avoiding full ablation of the tissue region.

[0024] Some example methods further include navigating a treatment device to a treatment location based in part on the visual marker. Example methods may further include performing electroporation using the electrolytic device positioned at the treatment location. In some example methods, a same electrode is used to perform electrolysis and to perform electroporation.BRIEF DESCRIPTION OF THE DRAWINGS

[0025] FIG. 1A is a schematic diagram of a medical procedure visualization system according to some examples.

[0026] FIG. IB is a schematic diagram of an ablation device according to some examples.

[0027] FIG. 2 is a schematic diagram of an ablation device and an imaging device according to examples described herein.

[0028] FIG. 3 is a flow chart of a method of medical procedure visualization using the medical procedure visualization system of FIG. 1.

[0029] FIG. 4 is a flow chart of a method of medical procedure visualization using the medical procedure visualization system of FIG. 1.

[0030] FIG. 5 is a schematic diagram of anatomy arranged in accordance with examples described herein.

[0031] FIG. 6A is a schematic diagram of an electrode as an anode according to examples described herein.

[0032] FIG. 6B is a schematic diagram of an electrode as a cathode according to examples described herein.

[0033] FIG. 7A is an example image of a medical procedure for visualizing a treatment site with an ablation device according to examples described herein.

[0034] FIG. 7B is an example image of a medical procedure for visualizing a treatment site with an ablation device according to examples described herein.

[0035] FIG. 8A includes example images of treatment sites using white light endoscopy according to examples described herein.

[0036] FIG. 8B is an example image of a treatment site using narrow band imaging (NBI) according to examples described herein.

[0037] FIG. 8C is an example image of a treatment site with histology showing regions of mucosal eruption correlating to electrode placement according to examples described herein.

[0038] FIGS. 9A-9C are example images of a treatment site of a small intestine of a pig after ablation using white light endoscopy according to examples described herein.

[0039] FIGS. 10A-10D are example images of a treatment site of a small intestine of a pig after ablation using white light endoscopy according to examples described herein.

[0040] FIG. 11 is a schematic diagram for a robotically-assisted servomechanism system, according to some examples.

[0041] FIG. 12A is a schematic diagram of an instrument system according to examples described herein.

[0042] FIG. 12B illustrates a distal portion of the instrument system of FIG. 12A with an extended example of an instrument according to examples described herein.

[0043] FIG. 13 is a perspective view of a manipulator system according to examples described herein.

[0044] FIG. 14 is a top view of a manipulator system according to examples described herein.DETAILED DESCRIPTION

[0045] Certain details are set forth below to provide a sufficient understanding of embodiments of the disclosure. However, it will be clear to one skilled in the art that embodiments of the disclosure may be practiced without these particular details. Moreover, the particular embodiments of the present disclosure described herein are provided by way of example and should not be used to limit the scope to these particular embodiments. In other instances, well-known materials, components, processes, controller components, software, circuitry, timing diagrams, and / or anatomy have not been described or shown in detail in order to avoid unnecessarily obscuring the embodiments.

[0046] Treatment mapping (e.g., visualizing treated areas) may be advantageous during and / or after ablation treatment. For example, ablation procedures in the lungs, , intestines, and other tissues may benefit from visualization of treatment. Examples described hereinprovide systems and methods that allow for visualization of treated tissue from endoluminal and other ablation procedures. Examples of systems and methods described herein may perform ablation and / or adjust ablation or other treatments based on the visualization of treated tissue.

[0047] For example, in order to ablate as much duodenopathy as possible given the dose dependent relationship with ablation and blood sugar level (A1C) reduction known to occur with DMR using thermal and IRE approaches along with the dose dependent relationship between lung function and the overabundance of goblet cells present in CB, techniques that provide users with the ability to map surface area of treatment zones with confidence of where to start a new or additional treatment zone are desired.

[0048] Examples of systems and methods described herein may be used with ablation technologies, such as endoluminal ablation procedures. In some examples, a technology for non-thermal intraluminal tissue ablation using a combination of electroporation and electrolysis (E2) may be used. Given this technology’s ability to regenerate the tissue back to normal with absence of collagen banding, scars, strictures (specifically in the small intestine) or ulceration, along with the ability to overlap zones of ablation without damage to underlying muscle, utilizing E2 for CB with lung treatment zone mapping or duodenal mucosal regeneration (DMRe) via treatment in the duodenum may be advantageous as a therapy for endoscopic treatment of endoluminal soft tissue ablation.

[0049] Examples described herein are with reference to endoluminal ablation, for example, to treat target tissues in the GI tract such the duodenum. However, it should be appreciated that ablation using a combination of electroporation and electrolysis with treatment feedback and / or visualization as described herein, may treat a variety of target tissues, such as in the intestines, duodenum, stomach, bladder, uterus, endometrial lining, ovaries, colon, rectum, sinuses, ducts, ureters, prostate, skin, muscle, nerve, diaphragm, momentum, kidney, follicles, brain, lymphatic vessels, breast, esophagus, lung, liver, kidney, lymph nodes, lymph node basins and / or heart or other target tissues.

[0050] Examples described herein include visualization techniques for tissue ablation, such as for endoluminal ablation or other target tissues. In some embodiments, the ablation may include a combination of electrolysis and electroporation. Treated tissue may have a different visual appearance at different charge densities used during an application of ablation, including ablation using electroporation with electrolysis. For example, tissue shortly after treatment using electroporation with electrolysis, particularly near an anode, appearsdiscolored. In some examples, the tissue after such treatment may appear white and / or lighter than prior to treatment. When tissue within a zone of a target region is treated using ablation with electroporation and electrolysis, the treated tissue changes color over time, e.g., from white to a reddish color. Imaging devices may be used to image the zone to identify treated regions within the zone by observing the treated tissue. In some embodiments, white light endoscopy may be used to image the zone, and the treated regions shortly after the treatment may appear discolored (e.g., white). In some embodiments, the imaging may be performed before, during, and after treatment. Confirmation of treatment can be obtained by observing coloration of treated tissue in images. Regions of tissue that were not treated, or were insufficiently treated, may be identified using their different coloration in contrast to treated regions. Based on a location of the treated regions, additional ablation may be performed at selected additional regions within the zone that were missed, using either manual techniques, or partially or wholly automated techniques. Note that tissue color changes due to energy application described herein may not be due to deleterious effects (e.g., charring or other undesirable side effects). In some examples, energy delivery to tissue at a level suitable for electroporation and electrolysis may cause tissue color changes described herein. For example, in some tissue ablation applications, radio frequency ablation (RFA) may be used to change the tissue color in a thermal manner to induce protein denaturation. In some sensitive organs, like duodenum or lung, however, introducing thermal energy, even solely to mark, may cause thermal spread that would travel transmurally through the intestinal or bronchial wall that causes fibrotic scarring, lack of local compliance, and / or stricture or perforation. For such organs, non-thermal ablation, such as electrolysis may be used for tissue marking given the ability to control the ablation depth. Because of resulting from a chemical effect, electrolysis-based coloration, such as marking, may potentially be performed with or without extensive cell death. In some examples, the electrolysis-based marking may be performed at a specific electrode (anode) within a bipolar device having a unique mechanism. For these reasons, electrolysis-based coloration may be used in the duodenum, lung or in any instance where thermal energy is risky.

[0051] In some embodiments, a degree of the ablation may be determined at the treated regions by one or more of image recognition, kinematic data, shape sensing data, and / or visual evaluation. Treatment via additional ablation may be adjusted at the region based on the degree of the ablation determined at the treated regions. Adjustments to the electroporation and / or electrolysis energy applied for additional ablation may include controlling at least one of applied energy (e.g., pulse) duration, a current applied, a charge applied (e.g., fieldstrength), voltage applied, a number of pulses, or a combination thereof. Optionally, in some examples, medication may be delivered to the treatment regions, including providing a pharmaceutical substance to or near the treatment regions. Medication delivery during treatment may be adjusted based on the appearance and position of treated tissue.

[0052] Examples of systems and methods described herein may be used for treatment planning for a desired region of target tissue. In some examples, identification of a treatment zone may be performed by marking a leading edge and / or a trailing edge of the zone using an ablation device to create physical markers. The ablation device may be used to apply energy in the form of electrolysis (with or without electroporation) at sufficient strengths to cause physical marking but without causing complete ablation at the marked areas. In other embodiments, the ablation device may apply other energy types or other ablation sufficient to cause marking. For example, the ablation device may apply energy at a location of a leading edge of a zone. This energy application may mark the leading edge of the zone by changing the appearance of the tissue at the leading edge. The ablation apparatus may be moved to a trailing edge of the zone, and energy application performed at the trailing edge of the zone. The energy application may mark the trailing edge of the zone by changing appearance of the tissue at the trailing edge. In some examples, the energy application used to mark regions of the zone may utilize an amount of energy that is also sufficient to treat the tissue (e.g., to ablate the tissue using electroporation and electrolysis to a particular depth). In some examples, the energy application used to mark may utilize less energy than an energy application which may be later used to treat tissue in the zone. In some embodiments, the leading edge and the trailing edge may be imaged by imaging using white light endoscopy and NBI for planning purposes. The leading and trailing edges may be compared with at least one of shape sensing data, kinematic data, or positional data. Based on the comparison, a treatment plan may be generated and an ablation device may be positioned between the leading and trailing edges based on the at least one of shape sensing data, kinematic data, or positional data to perform the ablation. In some embodiments, the ablation device may be positioned in a manner that an electrode, such as the most distal electrode, may be positioned at the leading edge and another electrode, such as the most proximal electrode, may be positioned at the trailing edge to provide an edge of ablation denoting where the zone stops and treatment was applied. The other electrodes, including anodes and cathodes may be layered between the leading and trailing edges.

[0053] In some embodiments, an initial scan of a target region may be performed by imaging using the imaging device to survey the target region. Proximal and distal markers may be setto indicate the region (e.g., zone) of desired ablation. The markers may be set virtually in the images from a user interface, or the markers may be set as leading and trailing edges provided by energy application or other physical marking as described herein. Energy application for marking may be performed using a manually operated delivery device, such as a guidewire catheter, to deliver an ablation device to target tissue. Alternatively, energy application may be performed using a robotically-assisted parent-child servo mechanism manipulator system to deliver an ablation device to target tissue. Ablation for treatment may then be performed either with a user moving an ablation device to target locations to apply ablation based on the visual feedback (the device may be delivered manually or under robotically-assisted control), or fully automatically in a robotically-assisted procedure where a servomechanism and / or computer processor controls treatment using the markers as start and stop locations, or in a semi-automatic manner in a robotically-assisted procedure where the processor may use a marker as a start position and an input by the user for a desired treatment length, or the user may select a start location without a specific marker applied and the processor may perform ablation-imaging loop until the system reaches the stop marker, etc. After the treatment has been applied, a post-treatment scan by imaging may be performed to identify any gaps or undertreated regions, which can then be retreated either by a user moving an ablation device (either manually or under robotically-assisted control) or movement occurring automatically using the system.

[0054] For example, a controller of a robotically-assisted servomechanism system may be used to position an imaging device to a location of the leading edge and image the leading edge of a treatment zone. A computing system may identify the leading edge of the zone, such as by identifying either a landmark or indicia of an applied physical marker (e.g., an electrolysis marker) at the leading edge of the zone based on images from the imaging device. A trailing edge of the zone may be identified in an analogous manner. The computing system and / or controller may further control the imaging device to move to a proximal portion of a zone to measure a travel distance from a trailing edge to the leading edge (e.g., either the landmark or the electrolysis marker). The computing system may generate a map including the zone, plan one or more treatment segments in the zone based on a position in the zone, a treatment location, the travel distance or combinations thereof. In some embodiments, the generation of the map may include anatomical positioning. In a medical procedure performed in accordance with the map, the computing system may be used to control the ablation device to move to and / or along the one or more planned treatment segments. During the medical procedure, the computing system may dynamically adjust one or more locations of the one ormore treatment segments based on images of the zone to update the planned one or more treatment segments. Thus, automated pre-operation planning and automated treatment may be performed.

[0055] In some examples, automated pre-operation planning and automated treatment using a robotically-assisted servomechanism system may be based on a reference of lineal travel that provides anatomical positioning for mapping, planning, confirmation and / or dynamically adjusting and updating. The reference of lineal travel may be obtained in some examples using one or more computer vision algorithms that identify treated regions using image analysis. Because the ablation examples described herein change the appearance of treated tissue in real-time upon tissue treatment, computer vision may be used to identify positions in the treatment zone and / or treatment locations. In some examples, the examples of systems and methods may utilize computer vision and a proximal marker and / or a distal marker that can be identified in the target region, with ablation to be performed between the proximal marker and the distal marker. In some examples, examples of systems and methods described herein may perform endoluminal ablation. In some examples, endoluminal energy application used may include electrolysis, a combination of electroporation and electrolysis, or other energy application or ablation types, which may mark the tissue to set the proximal and distal markers.

[0056] For example, energy application using an endoluminal ablation device may be performed to mark the leading and / or trailing edges of a treatment zone for the purposes of creating a visible marker of treated tissue (e.g., using electrolysis with or without electroporation). Additionally or alternatively, characteristic landmarks can be identified in the target region to be used for the proximal and / or distal markers. Additionally or alternatively, physical markers may be set by application of other energy types (e.g., RF or thermal energy) or physical scoring, etc. One or more computer vision algorithms, such as Visual Simultaneous Localization and Mapping (SLAM) and / or You Only Look Once (YOLO) may be used for anatomical positioning for mapping the target regions using the markers. In some examples, such imaging may be assisted by introducing a frame of reference for imaging. For example, an ablation device or a catheter with cm or mm markings may be imaged and used as a frame of reference in some examples. In this manner, one or more images may include a known reference scale that may be used as a registration marker to measure movement of an ablation device including an elongate flexible device (e.g., an endoscope and / or catheter). Based on the images including the scale, movement of the ablation device in a lumen or cavity may be visualized as a length.

[0057] In some examples, training algorithms and software to be executed to treat regions of disease may be performed using artificial intelligence (Al) and / or machine learning (ML), such as SLAM and / or YOLO. For example, a computing system may create a model for a target disease and / or treatment (e.g., DMR). Training the model may include training a model of Al and / or ML using images of treated regions with annotated positional and / or kinetic data or other clinical data related to a target disease and / or treatment from a pool of patients. In this manner, the trained model may be trained to identify the tissue changes which occur in a particular disease and / or treatment responsive to endoluminal ablation. Planning ablation treatment by the trained program or algorithm with the model may use the images with positional and / or kinetic data or any clinical data from a target patient. Thus, positioning the ablation device in a zone for treatment may be performed.

[0058] Examples of systems disclosed herein may include an ablation device including electrodes to contact tissue and / or be positioned in proximity to tissue. The ablation device may perform ablation of the tissue. Examples of systems may include an imaging device in proximity to the ablation device that images a zone to identify treated and / or marked regions within the zone. The imaging device may be implemented using generally any imaging system, including those utilizing white light endoscopy, NBI, fluorescence, chromoendoscopy, optical coherence topography (OCT) or radial ultrasound or a combination thereof. In some embodiments, the imaging device may include an ultrasound imaging sensor and light source. In some embodiments, examples of systems may include an endoscope including the imaging device. The electrodes may be distally attached to the endoscope.

[0059] Examples of systems disclosed herein may include a controller coupled to the ablation device and optionally to the imaging device. The controller may control the ablation device to treat tissue within a treatment zone by controlling a charge applied to the plurality of electrodes, control the imaging device to image the zone, and based on a location of the treated regions determined based on imaging of the zone, control the ablation device to perform additional ablation at selected additional regions within the zone. In some embodiments, at least one electrode may be inserted through a working channel of an endoscope. Examples of systems disclosed herein may include a catheter and an expandable member at a distal portion of the catheter. Example systems and methods may be applied to endoluminal ablation applications or other bodily tissues.

[0060] Examples of systems disclosed herein may include a computing system, which may include at least one processor. The computing system may receive data including images from the imaging device and perform image recognition to identify the treated regions. Theprocessor may tag portions of images to select additional regions to be treated. For example, the tagged portions may be compared (by the computing system) with kinematic data from a robotic system used to perform the ablation, and the processor may generate position data for the selected additional regions based on comparing. The processor may control the controller to perform additional ablation. The processor may use the position data to position the robotic system to treat the selected additional regions. In some examples, the processor may compare the leading and / or trailing edges with at least one of shape sensing data, kinematic data, or positional data, and positioning an ablation device between the leading and trailing edges based on the at least one of shape sensing data, kinematic data, or positional data to perform the ablation. While in some examples a single computing system and / or processor may be described, it is to be understood that the implementation scenarios are quite flexible, and any number of computing systems and / or processors may be used. The computing systems and / or processors may be communicatively coupled to perform the actions described herein in some examples.

[0061] Examples of systems disclosed herein may include a display configured to display one or more images generated by the imaging device, and the controller may allow a user to perform visual evaluation to determine a degree of ablation at the treated regions and / or a location of treated regions.

[0062] In some examples, imaging the treated regions may result in a computing system and / or visual observer to direct an ablation device to perform additional ablation of untreated and / or undertreated regions. Coloration, which may arise from a reaction of tissue to substances from electrodes, may in some examples be observed instantaneously during and / or after treatment with imaging techniques described herein. Furthermore, applying energy may be utilized for marking on tissues for pre-operative planning of locations to treat, followed by treatment and feedback of coloration via the treatment for further treatment. Using energy application and ablation techniques for visualization and identification of treated regions, treatment confirmation and planning may be provided.

[0063] FIG. 1 A is a schematic illustration of a system 100 for providing medical procedure visualization and ablation according to some examples. FIG. IB is a schematic illustration of an ablation device 120 in the system 100 according to some examples. Generally, examples of systems described herein may include a controller and an ablation device. In the example of FIG. 1 A, the system 100 includes a controller 104, the ablation device 120, and an elongate flexible device 130, such as a catheter or endoscope, that may be coupled to the ablation device 120. In some embodiments, the controller 104 may be coupled to the elongate flexibledevice 130. Examples of ablation device 200 are described in further detail in regard to FIG. 2. In some examples, the elongate flexible device 130 is a manual guidewire catheter actuated by hand. In other examples, the elongate flexible device 130 is a flexible catheter, endoscope, duodenoscope, or other device that is robotically driven, for example by a robotically-assisted servomechanism system as described in further detail with respect to FIGS. 11-12B. In such a system, the elongate flexible device 130, such as a flexible catheter or endoscope, is coupled to a drive unit (e.g., drive unit 1204) which receives actuation forces from a manipulator assembly (e.g., manipulator assembly 1102). The ablation device 120 may be an end effector for a flexible ablation instrument (e.g., instrument 1226) that extends through a working channel of the elongate flexible device 130 or along the elongate flexible 130. In some implementations, the ablation device 120 may optionally be a removable attachment that is coupled to a distal end of the elongate flexible device 130.

[0064] The ablation device 120 includes one or more electrode members 15 and optionally one or more expandable members 14, such as balloons. In some examples, the ablation device 120 may include an imaging device 18. In some examples, the imaging device 18 may be implemented as part of the elongate flexible device 130, (e.g., a catheter or endoscope), as part of the ablation device 120, or as part of a separate instrument. The imaging device 18 may trail the ablation device 120 once the ablation device 120 is introduced to target tissue 10, such as tissue of the small intestine or other tissues. In some examples, the imaging device 18 may be advanced to the target tissue 10 and the ablation device 120 may be controlled to trail the imaging device 18. In some examples, the electrode member 15 may surround the expandable member 14. The expandable member 14 may be used to provide an outward tissue apposition force to the electrode member 15, to ensure sufficient contact between the electrode member 15 and the target tissue for electrolysis products to diffuse into the target tissue. The electrode member 15 may include one or more electrodes 16 disposed at a distal portion and a proximal portion of the electrode member 15. The one or more electrodes 16 may be used to provide ablation, such as both electroporation and electrolysis in some examples. The ablation device 120 coupled to the elongate flexible device 130 may be introduced to a targeted tissue for ablation for delivery of electrolysis products, and regeneration, such as the cavity 12 of tissue 10 within an endoluminal zone of a patient. The expandable member 14 may be pressed against the tissue 10 and the one or more electrodes 16 may perform ablation. Although the electrode member 15 is shown disposed within the cavity 12 of the tissue 10, the electrode member 15 may be on the surface of the tissue 10, inside the tissue 10, and / or proximate to the tissue 10. Moreover, although the elongateflexible device 130 is shown being used to position the one or more electrodes used for permeabilization and / or the generation of electrolysis products, in other embodiments, other ablation devices may be used and / or the electrode(s) may be positioned proximate to the tissue in other ways — e.g., by contacting the tissue with electrode(s) or using a probe, a pad, needle electrodes, flexible laparoscopic electrodes, or another device coupled to the one or more electrodes to bring the one or more electrodes proximate to the tissue.

[0065] The controller 104 may include one or more processor(s) 106, computer-readable media 108 (e.g., memory), and other computing system components, such as one or more input devices, output devices, sensors, and / or communication devices in some examples. Additional, fewer, and / or different components may be used in other examples. The computer-readable media 108 includes executable instructions for ablation 110, such as electroporation and electrolysis with the one or more electrodes 16. In some embodiments, executable instructions for ablation 110 may include controlling an electrode member 15 to treat tissue within a zone of target tissue using endoluminal ablation by controlling a charge applied to the one or more electrodes 16. The computer-readable media 108 may include parameters 114 that may be selected in the process for controlling the electrode member 15. For example, the parameters 114 may include a duration, a voltage or range of voltages, a number of pulses, or combinations thereof, to be applied on the treated regions based on the degree of ablation to control charge on the one or more electrodes 16. In some examples, electric field strengths, current levels, capacitance, waveform shapes, etc., may also be selected.

[0066] The computer-readable media 108 includes executable instructions for imaging 112. The executable instructions for imaging 112 may include controlling the imaging device 18 to image the zone of the target tissue. In some embodiments, the imaging device 18 may be included in the ablation device 120. In some embodiments, the imaging device 18 may be an endoscope trailing the ablation device 120. In some embodiments, imaging may use white light endoscopy, NBI, fluorescence, chromoendoscopy, OCT or radial ultrasound or a combination thereof. The imaging device 18 may be contactless for white light endoscopy, NBI, and / or fluorescence, as long as wavelengths of a light source of the imaging device 18 are configured for identifying colors. The imaging device 18 performing depth mapping using OCT or radial ultrasound may be included in the ablation device 120 to be in contact with the treated regions.

[0067] The controller 104 may be implemented using a computing device. Examples of computing devices include controllers, microcontrollers, computers, servers, medical devices,smart phones, tablets, wearable devices, and the like. The computing device may be handheld and may have other uses as well.

[0068] The controller 104 may include one or more processors, such as the processor 106. Any kind or number of processors may be present, including one or more central processing unit(s) (CPUs) and / or graphics processing unit(s) (GPUs) having any number of cores, controllers, microcontrollers, and / or custom circuity such as one or more application specific integrated circuits (ASICs) and / or field programmable gate arrays (FPGAs).

[0069] The controller 104 described herein may include the computer-readable media 108, such as memory. Any type or kind of memory may be present (e.g., read only memory (ROM), random access memory (RAM), solid state drive (SSD), secure digital card (SD card), and the like). While a single box is depicted schematically as the computer-readable media 108 in FIG. 1 A, any number of computer-readable media 108 devices may be present. The computer- readable media 108 may be in communication with (e.g., electrically connected to) the processor 106.

[0070] The computer-readable media 108 may store executable instructions for execution by the processor 106, such as executable instructions for ablation 110 with the electrode member 15 utilizing stored parameters 114 for charging the one or more electrodes 16. In this manner, techniques for applying E2 in tissue may be implemented herein wholly or partially in software. The executable instructions may include instructions to control a charge delivered to electrodes, such as electrodes 16 of the electrode member 15. Accordingly, the controller 104 may induce a voltage difference across the targeted tissue to generate an electric field that causes permeabilization of cells in an area of tissue targeted for treatment. The executable instructions for ablation 110 may further include instructions to control the ablation device to perform additional endoluminal ablation at selected additional regions within the zone, based on a location of the treated regions determined based on imaging of the zone.

[0071] Generally, electrodes used in examples described herein may be used in a monopolar configuration, or a bipolar configuration, or combinations thereof. Generally, a monopolar configuration may include an active electrode (e.g., an electrode on or in the surgical field) and a return electrode. In some embodiments, the active electrode may be an anode. The return electrode may be placed outside the surgical field but in contact with the patient in some examples (e.g., using a pad having an electrode). In this manner, one polarity (e.g., the polarity of the active electrode) is in the surgical field. Accordingly, a monopolar configuration of electrodes may include a pair of electrodes — with one electrode energizedand one electrode serving as a return. The return electrode may be provided on different device than the energized electrode. For example, the return electrode may be provided on a pad placed on the patient’s skin. In a bipolar configuration, current may travel from one electrode of a pair of electrodes to another electrode of the pair of electrodes. The electrodes in the pair may accordingly be said to be of opposite polarity. Multiple pairs of electrodes may be used. In some examples, a monopolar configuration of electrodes may include any combination of active and return electrodes, including different numbers of active electrodes and return electrodes. For example, a number of active electrodes may be greater than a number of return electrodes, or vice versa. Generally, a monopolar configuration may refer to the use of one or more active electrodes (e.g., electrodes positioned proximate the tissue to be treated) energized relative to one or more distant electrodes (e.g., placed externally to a patient being treated). In a monopolar configuration, multiple active electrodes may be present and may pass current through a shared return electrode in some examples, or through respective return electrodes in other examples. In a bipolar configuration, in some examples, current may be passed through multiple pairs of electrodes. In some examples, a distally positioned electrode may be used as an anode and a proximally positioned electrode may serve as a cathode. In some examples, a distally positioned electrode may be used as a cathode and a proximally positioned electrode may serve as an anode. In some examples, a bipolar configuration of electrodes may include any combination of anodes and cathodes, including different numbers of anodes and cathodes. For example, a number of anodes may be greater than a number of cathodes, or vice versa. In some examples, electrodes used in examples described herein may include treatment electrodes and electrodes used to create visual markers. These treatment and marker electrodes may be independent from each other (i.e., separate electrodes for treatment than for marking), the electrodes may be common for treatment and marking, or there may be some electrodes that contribute to both treatment and marking while other electrodes are used for treatment only or marking only. For instance, ablation may be performed with a bipolar configuration followed by tissue marking with a monopolar configuration and the same end-effector. Alternatively, the opposite could be true. Or following ablation with a bipolar or monopolar configuration, the anodes and the cathodes may be changed in some manner to deliver visualization pulses. In further examples, separate electrodes on a common end effector may be used for marking than for treatment, or a first end effector applying marking and a second end effector applying treatment.

[0072] A controller, such as the controller 104 of FIG. 1 A, may activate one or more selected electrodes in order to provide an electric field as described herein. In some examples, thecontroller 104 may activate an electrode that may serve as an anode. The controller 104 may alternate or otherwise select a pattern of activated electrodes (e.g., activating pairs of electrodes in sequence) to shape or deliver a particular electric field. In some embodiments, one or more of the electrodes used to apply electroporation may also be used to generate products of electrolysis (e.g., some or all of the electrodes may be used for both electroporation and electrolysis), while in other embodiments, the electrodes used to apply electroporation may be different than the electrodes used to generate products of electrolysis. Generally, any shape of electrodes may be used, including circular, square, rectangular, or other shapes. In some examples, the shape of the electrodes may be determined based on a shape of regions to be visualized. The controller 104 may also be used to induce a current through the tissue, such as between electrodes, to generate products of electrolysis. The products of electrolysis may cause ablation of the permeabilized cells. The products of electrolysis may be insufficient to destroy the extracellular matrix in the region of the permeabilized cells, and accordingly the permeabilized cells may be ablated while leaving an extracellular matrix in the region intact. The intact extracellular matrix may allow for colorations of the tissue and further tissue engineering.

[0073] In some embodiments, the one or more electrodes 16 used in examples may include an anode. When the imaging device 18, such as an endoscope, images the treatment zone, treated regions by ablation in proximity to the anode may appear discolored (e.g., white) in contrast to untreated regions within a short period after the treatment. In some examples, treatment regions in proximity to the anode may change color from the untreated tissue color to a white color. Using white light endoscopy, the treated regions may be effectively visualized via the color change and gradations of the color change. In some examples, some other imaging techniques, such as NBI, fluorescence, chromoendoscopy, OCT and / or radial ultrasound may be used to visualize the treated regions as well as untreated or insufficiently treated regions to visualize different colorations and gradations.

[0074] The system 100 may include a power supply 102. The power supply 102 may be coupled to the controller 104. The power supply 102 may be implemented using one or more AC power sources, DC power sources, batteries, and / or waveform generators. The power supply 102 may supply power to one or more electrodes 16 to generate a voltage and / or current and, therefore, an electric field and / or electrolysis products in the tissue. In some examples, the power supply 102 may be implemented using a signal generator, such as an exponential decay wave generator (by way of example, a Harvard Apparatus BTX 630); however, this disclosure is not limited thereto or thereby. In some examples, a signal generatormay include a bank of capacitors to select from, as controlled by the controller 104. The signal generator may allow for selection of a specific charge (e.g., capacitance) per application of the charge.

[0075] The controller 104 may control the timing, strength, and duration of electric fields and / or electrolysis products provided by the electrode member 15. The controller 104 may, for example, be programmed to provide an electronic signal to the electrode member 15 through the elongate flexible device 130. The electronic signal may be indicative of a dose of treatment, for example, a dose of electrolysis products. The electronic signal may control the timing and magnitude of a current generated by the one or more electrodes 16 of the electrode member 15 to generate an electric field. This may allow a user to customize treatment of the tissue 10. In some embodiments, the controller is coupled to a power supply 102. In some embodiments, the power supply 102 may be included in the medical procedure visualization system 100. In some embodiments, the power supply 102 is integrated with the controller 104.

[0076] Although shown as a separate component coupled to the ablation device 120 via the elongate flexible device 130, in some embodiments, the controller 104 may be integrated into the ablation device 120. In some embodiments, the controller 104 may include programmable circuitry coupled to the ablation device 120. The controller 104 may be coupled by a wire or communicate with the ablation device 120 wirelessly.

[0077] In some embodiments, the controller 104 may be programmed to provide an electronic signal indicative of a dose of the electrolysis products and / or permeability level of a cell. The controller 104 may, for example, include such a program, or include one or more processing devices (e.g., processors) coupled to the computer-readable media 108 encoded with executable instructions for ablation 110.

[0078] Examples of voltages, currents, time durations and / or time constants, electric field strengths, capacitance, and / or a number of pulses may be calculated and / or determined in accordance with methods described herein. In some examples, parameters, such as parameters 114 of FIG. 1A, may be determined based on measurements taken in the tissue of interest, or a different sample of similar tissue of the same patient or a different patient. For example, measurements may be taken at various voltage levels with particular electrode configurations, and a voltage level, current, pulse pattern, time constant, and other factors may be identified that cause reversible electroporation and the delivery of electrolysis products to result in cell death of the permeabilized cells. Generally, electric fields may be generated in tissue that maycause reversible electroporation of cells in a target ablation area. Electrolysis products may be generated and may diffuse for a time to cause ablation of the permeabilized cells, but to leave intact the extracellular matrix in the region of the ablated cells.

[0079] Examples of parameters that may be used include a delivery of between one and 10 or more voltage pulses between 10 V and 5,000 V. In some examples, ranges of parameters may depend upon the tissue target and the end effector design. Those pulses may be delivered in a system in some examples having a capacitance between 1 pF and 1500 pF as selected by the signal generator. In some examples other capacitance values may be used. In some examples the pulses may be delivered using a resistance of between 15-20 ohms, for example. Other resistance values may be used in other examples. In some examples, electric fields between about 1,500 V / cm and about 0 V / cm may be generated in tissue. A quantity of electrolysis products generated may be related to the delivered charge in Coulombs. There are several ways to calculate the delivered charge. For example, the stored electric charge in a capacitor Q (in Coulombs, abbreviated C) is generally equal to the product of the capacitance C (in Farads, abbreviated F) of the capacitor, and the voltage V (in volts, abbreviated V) across its terminals. That is, Q = O V. The stored electric charge is generally equal to the product of the current I (in amperes, abbreviated A) and the time t (in seconds, abbreviated s). That is, Q = I • t (e.g., when a pulse is a constant- current pulse) or Q = f I(t)dt. By defining the capacitance and the voltage across the capacitance, the charge may be defined, and accordingly the electrolysis performance determined. When a capacitor is discharged, the capacitor generates current and the current multiplied by time must be equal to the total charge in the capacitor. When a capacitor is being discharged, the current is not constant — the current decays exponentially. Therefore, the time measure is given as the exponential decay time constant, and the current measure is given as the peak current at the instant the discharge begins. The capacitance that controls the time constant is generally obtained in examples described herein from capacitors incorporated in the power supply, such as power supply 102 of FIG. 1A. Thus, the time constant (e.g., exponential decay time constant of the capacitive discharge) may be controlled.

[0080] In some examples, parameters used to ablate tissue using electroporation and electrolysis techniques described herein may utilize significantly less charge per volume of tissue targeted for treatment than when electrolysis alone is used for ablation (in addition, electrolysis alone may cause scarring and / or other impediments to tissue regeneration). Furthermore, parameters used to ablate tissue using electroporation and electrolysistechniques described herein may utilize significantly lower electric field strength targeted than when IRE ablation is performed for treatment.

[0081] In some examples, energy delivery, such as by electrolysis (with or without electroporation), may be provided at dosages and for an amount of time sufficient to allow coloring (e.g., discoloration) of a region of permeabilized cells to provide physical markers to tissue without causing complete ablation of the tissue for treatment. In some examples, the energy used to provide markers may be insufficient to damage extracellular matrix in the region of the ablated cells. Thus, it may be possible to apply energy to mark the tissue for use as indicators for treatment planning as described herein without fully treating the tissue (such as by ablating a volume of tissue). Accordingly, energy delivery to the tissue may be provided for ablation, marking, or both. An electrolytic device (e.g., a device capable of performing electrolysis) may be positioned proximate a tissue region for visual marking. Electrolysis may be performed, changing a visual appearance of the tissue (e.g., discoloring the tissue), thereby creating a visual marker. Marking without full tissue treatment may be achieved by various energy delivery parameters, such as ablating with shorter time periods and relatively higher amplitude pulses, or longer time periods with lower amplitude pulses, in each case the delivery parameters adjusted to avoid full ablation of the target regions. Marking of tissue may occur through an electrochemical process. In some examples, electrochemical interactions may be dependent upon a total amount of electrons supplied or removed at an electrode-electrolyte interface of tissue. The extent of reactions to the electrochemical interactions may be controlled by manipulating an amount of charge delivered through a specified control volume of tissue and / or surface area of electrode. In some examples, ablation may use both a threshold electric field of several hundred V / cm and additional electrolysis (charge). In some examples, marking of tissue to provide visual markers may be performed by passing sufficient charge alone at specified locations through the tissue in a low-voltage manner without significant damage to the tissue due to the absence of electroporation. Thus, transient visual markers may be provided at the electrode-tissue interface without volumetric cell death. Such transient visual marking technique may be useful where the user would like to create a guiding marker that is not immediately at the boundary of an ablated zone, such as to provide a buffer of untreated tissue between subsequent ablations. The transient visual marking technique may also allow a user to create a marker to test whether an electrode is in the desired location visually prior to delivering ablative energy, and to adjust the electrode location without ablation. In some examples, a charge-balanced (e.g., biphasic) waveform for ablation without creation of discoloring maybe used in both electroporation and electrolysis. Following the ablation, a low-voltage, higher-charge waveform may be delivered to visualize regions of electrode contact without further cell damages, thus a user may infer the regions of ablation. There are numerous other advantages of transient visual marking not limited to examples described herein.

[0082] While examples of electroporation and electrolysis are described as ablation techniques use in connection with visualization described herein, in other examples other endoluminal ablation techniques may be used including electrolysis, electroporation, thermal ablation, or other ablation techniques.

[0083] The parameters may be stored in the computer-readable media 108 as parameters 114. The controller 104 in some examples may be used to calculate the parameters 114. In other examples, the parameters may be calculated by another system and may be provided to and / or stored by the controller 104.

[0084] The system 100 may further include one or more sensors (not shown) for measurement of pH, electric field strength, and / or other properties of the tissue 10. For example, a pH sensor may be provided. The pH sensor may in some examples be located on and / or attached to the delivery system, such as the ablation device 120 of FIGS. 1A and IB. In some examples, a pH sensor may be positioned near electrodes of the delivery system, such as one or more electrodes 16 of FIGS. 1A and IB. A pH value near the one or more electrodes may accordingly be detected. In some examples, one or more electrodes 16 may function as an anode being acidic having a pH value less than seven. In some examples, one or more electrodes 16 may function as a cathode being basic having a pH value greater than seven. The pH sensor may be coupled to the controller 104, and the detected pH value provided to the controller 104. Additionally or alternatively, a pH sensor may be provided at an outer edge of a targeted region of tissue. The pH sensor may be coupled to the controller 104, and the detected pH value provided to the controller 104. Additionally or alternatively, a pH sensor may be provided at a particular site in the tissue to detect pH at the particular location, such as a location at which tissue damage is not desired. The pH sensor may be coupled to the controller 104, and the detected pH value provided to the controller 104. The controller 104 may utilize one or more received pH values as an indication of tissue ablation and / or potentially damaging pH levels that may cause, or be close to causing, tissue damage. The controller 104 may combine the pH values in any manner. For example, the controller 104 may take a difference between received pH values (e.g., a pH value near an edge of a targeted tissue region and a pH value near an electrode). The controller 104 may adjust the voltage, current, and / or electric field applied to the tissue responsive to the pH level or combinationof pH levels. For example, if a pH value at a location where tissue damage is not desired is at or beyond a threshold for tissue damage, the controller 104 may reduce a magnitude of electric field or a duration between pulses, or cease application of the electric field. In some examples, if a pH value in a region where tissue ablation is desired is at or beyond a threshold for tissue ablation, the controller 104 may cease application of current through electrodes immediately and / or after a desired elapsed electrolysis time to cease the electrolysis process.

[0085] Additionally, a resistivity meter may be used to determine a resistance of the target tissue. A resistivity meter may be provided, for example, on or otherwise coupled to the delivery system. For example, the controller 104 and / or power supply 102 of FIG. 1A may provide an impedance measurement. The impedance measurement may determine a resistivity of the tissue contacted by electrodes 16 of the ablation device 120. For example, the controller 104 and / or power supply 102 may provide a nominal amount of current, such as DC current, through the tissue and receive a resistivity measurement and / or calculate resistivity of the tissue. In some examples, an applied voltage, current, capacitance, and / or electric field may be selected, determined, and / or allowed based on a measured resistance of the tissue. In some examples, a number of pulses of applied voltage may be selected, determined, and / or otherwise used based on a measured resistance of the tissue. In some examples, a number of pulses may range from one to 10, 20 or 30.

[0086] A number of pulses may be selected to provide a particular dose (e.g., surface charge) that may control a depth of ablation and / or a ratio of circumferential ablation (e.g., an amount of ablation within a particular circumference may increase). For example, a delivered charge for a number of pulses may be calculated. For example, the electric charge provided from a capacitor for the number of pulses Q (in Coulombs, abbreviated C) may generally be equal to the product of the capacitance C (in Farads, abbreviated F) of the capacitor, the voltage V (in volts, abbreviated V) across its terminals, and a number of pulses N (is a natural number from one to 10, 20 or 30, or more in some examples). That is, Q = C 'V'N. By selecting a number of pulses, a depth of ablation and / or a ratio of circumferential ablation may be controlled. Devices described herein may control a number of delivered pulses (e.g., voltage pulses) based on a particular depth and / or ratio of circumferential ablation. Generally, the amount of circumference of tissue affected by ablation may increase with an increased number of pulses applied. Despite increasing ablation, the generation of heat may be reduced and / or avoided by use of the combination of reversible electroporation and electrolysis. The surface charge applied may be a fraction of the surface charge typically used if only electrolysis were used to achieve ablation.

[0087] In some examples, a sensor for detecting and / or determining electric field strength may be used. The strength of the electric field at any point is found by measuring the potential difference between adjacent equipotential lines and dividing by the distance between them. The distance between the lines is taken along the electric field lines that are perpendicular to the equipotential lines. Gauss meters and / or Tesla meters may be used for this purpose in some examples.

[0088] During operation, electrodes 16 may be brought into proximity of tissue. The electrodes may contact the tissue, be implanted in the tissue, or be positioned on, adjacent to, or near the tissue. For example, the ablation device 120 including electrodes 16, may be delivered to a patient to bring the electrodes proximate to tissue.

[0089] In some embodiments, visualization of a zone of tissue, delivery of the electrodes 16 into proximity of tissue, and treatment of a zone of tissue may be performed manually using the system 100. For example, a user, such as a clinician who uses the ablation device 120, may use direct visualization of the zone by the imaging device 18 during a procedure. The user may manually advance and place the ablation device 120 under direct vision to treat skip lesions and / or avoid overlapping zones of ablation. When the user notices a skip lesion, the user may reposition the delivery system to perform additional ablation to treat the skip lesion.

[0090] The user may map treatment based on the direct visualization of the zone throughout the procedure for better intraprocedural planning in some examples, such as performing additional ablation of tissue outside the treated regions. In some embodiments, pre-operative planning could also be implemented with duodenopathy identified by a screening endoscopy to identify patients who may respond best to the therapy.

[0091] In some embodiments, some or all of the visualization of a zone of tissue, delivery of the electrodes 16 into proximity of tissue, and treatment of a zone of tissue may be performed under robotically-assisted control. In some examples, direct visualization of the zone may be utilized by a user to actuate the ablation device 120 using a user input (e.g., operator input system 1106) coupled to a servomechanism assembly to move the ablation device 120 under robotic assistance, including the imaging device 18, the electrode member 15 and / or the elongate flexible device 130 to the region of ablation to allow for precision to avoid treatment gaps or overlapping zones of ablation. In some examples, the processor 106 or an external computing device coupled to the controller 104 may autonomously perform visualization of the zone using, for example, image recognition, and may automatically control movement of the elongate flexible device 130 based on the output of the imagerecognition. For example, image recognition may output an identification of a region of missed treatment, and the external computing device may control movement of the elongate flexible device 130, to the region of missed treatment to allow for treatment of the missed region.

[0092] In some embodiments, visualization and positioning of the elongate flexible device 130 may be based on shape sensing, kinematic data and / or positional data of devices in the elongate flexible device 130 and / or the zone for treatment to precisely place and appose electrodes 16 to perform endoluminal ablation. Robotic systems, such as the processor 106 or an external computing device coupled to the controller 104 may execute planning software to construct two-dimensional (2D) and / or three-dimensional (3D) regions of duodenopathy using screening data (which may be obtained by a screening endoscopy and / or via mapping during a procedure using the elongate flexible device 130 to map target tissue). The robotic systems may use kinematic data and / or positional data in real-time to track treatment zones and treatment progress for enhanced efficacy in real-time. In some examples, the robotic systems may generate reports for the user regarding a portion of or a total area or volume of tissue (e.g., duodenopathy) treated. The reports may be used to correlate the total area or volume of treatment (e.g., duodenopathy) treated with dosimetry to outcome (e.g., A1C reduction and / or improved glycemia via continuous glucose monitoring and time-in-range metrics).

[0093] Utilizing positional and kinematic data in combination with intraprocedural mapping of the duodenal inner diameter and total desired ablation length, a program executed by the processor 106 or the external computing device coupled to the controller 104 may provide feedback for a user to control of the system under robotic assistance. In some embodiments, the robotic system may autonomously move the robotically actuated elongate flexible device 130 to each planned treatment zone. The processor 106 or the external computing device may compute a distance to move the robotically actuated elongate flexible device 130 based on at least some of positional, kinematic data, and shape sensing data in combination with intraprocedural mapping. The processor 106 or the external computing device may provide the computed distance to the user in order to assist the user in some examples to accurately place and reposition the elongate flexible device 130. For example, rather than autonomously moving the elongate flexible device 130 via the controller, the user may use the operator input system 1106 to control movement of the robotically actuated elongate flexible device 130 to perform ablation. The processor 106 or the external computing device may further provide information about movement and apposition of the robotically actuated elongate flexibledevice 130 to inform axial or rotational deployment for optimal circumferential ablation and treatment zones to assist the control by the user.

[0094] In some examples, the processor 106 or the external computing device may use the images to do one or more of the following: determine untreated regions, provide feedback to the user about untreated or under treated regions and / or perform treatment by ablation of the untreated regions, image tissue within the zone, obtain reconstructed 2D or 3D regions, and obtain images of side views of ablated tissue within the zone from the reconstructed 2D or 3D regions. The processor 106 or the external computing device may identify the treated regions in the images and tag undertreated or untreated regions in the zone in the images. For example, a color associated with treated regions may be a different than a color associated with untreated regions. The color difference may, in some examples, be based on time. For example, within a particular amount of time after treatment, tissue regions treated with electroporation and electrolysis ablation may appear discolored, while untreated tissue appears pink. Within a further amount of time after treatment, tissue regions treated with ablation may appear a darker red than untreated tissue. Accordingly, the processor 106 may execute instructions to identify regions of tissue having a different color than other regions of tissue. The regions of tissue having a whiter and / or darker red appearance may be tagged as treated regions. The processor 106 or the external computing device may correlate or associate tag information of images (e.g., positions of the tags in the images) to positional and kinematic data in combination with intraprocedural mapping of the duodenal inner diameter and total desired ablation length, and autonomously move the electrode member 15 using the axial or rotational deployment for optimal circumferential ablation and treatment zones by controlling movement and apposition of the robotically actuated elongate flexible device 130 . In some examples, optionally, the processor 106 or the external computing device may control an initial imaging and initial treatment autonomously. After the initial treatment, the processor 106 or the external computing device may continue performing the feedback loop of using the images to determine untreated regions followed by the further treatment of untreated regions until the entire zone is treated.

[0095] In some examples, Al and / or ML, such as SLAM and / or YOLO, may be used to train algorithms and software to be executed by the processor 106 or the external computing device to treat regions of disease. For example, a model of Al and / or ML may be trained using images of treated regions with positional and / or kinetic data or any clinical data related to a target disease for treatment from a pool of patients to create a model for the target disease. The processor 106 or the external computing device executing the trained program or algorithmwith the model may use the images with positional and / or kinetic data or any clinical data from a target patient to plan ablation treatment. Thus, the ablation device 120 may be positioned in a zone for treatment using the medical procedure visualization system 100.

[0096] When the ablation device 120 is positioned in a zone for treatment, an electric field may be applied via one or more electrodes 16 to target anatomy in order to provide precise, accurate, and repeatable ablation in open, laparoscopic, thoracoscopic, and / or robotically- assisted procedures. For gastrointestinal applications, the ablation device 120 may be delivered via a manual or robotic delivery device endoluminally through a trans-oral or trans- anal approach or trans-abdominally with integrated bipolar instrumentation, drop-in probes, or via catheters. For urological applications, the ablation device 120 may be delivered via a manual or robotic delivery device endoluminally through a trans -urethral, trans-perineal, pre- peritoneal, or trans-abdominal approach with integrated bipolar instrumentation, drop-in probes, or via catheters. For gynecological applications, the ablation device 120 may be delivered via a manual or robotic delivery device endoluminally through a trans-vaginal, trans-perineal, or trans-abdominal approach with integrated bipolar instrumentation, drop-in probes, or via catheters. For hepatobiliary applications, the ablation device 120 may be delivered via a manual or robotic delivery device endoluminally through a trans-oral approach to reach the ampulla or to go externally into the liver via a trans-gastrointestinal wall route or a trans-abdominal approach with integrated bipolar instrumentation, drop-in probes, or via catheters. For neurovascular applications, the ablation device 120 may be delivered via a manual or robotic delivery device through an endovascular approach or through a keyhole craniotomy with integrated bipolar instrumentation, drop-in probes, or via catheters. For cardiac applications, the ablation device 120 may be delivered via a manual or robotic delivery device through an endovascular or a trans-thoracic approach with integrated bipolar instrumentation, drop-in probes, or via catheters. In case of endobronchial ablation in a lung for treatment of chronic obstructive pulmonary disease, such as chronic bronchitis and emphysema, the ablation device 120 may be delivered via a manual or robotic delivery device endoluminally through a trans-nasal or trans-oral approach with integrated bipolar instrumentation, drop-in probes, or via catheters.

[0097] The process of applying the electric field to control ablation, such as causing permeabilization and performing electrolysis may be controlled by computing systems described herein, such as the controller 104 of FIG. 1A in accordance with the executable instructions for ablation 110. An electric field may be applied to at least a portion of the tissue using the electrodes 16. For example, the controller 104 may apply voltages to the electrodes16 to apply the electric field. In some examples, fluids or other substances may be injected into, brought into contact with, or otherwise placed in or around the tissue to aid in shaping the electric field generated in the tissue. The electric field may be of a strength in the tissue to cause reversible electroporation in a region of cells targeted for ablation. Accordingly, cell membranes in an area of tissue targeted for ablation may be permeabilized. The electric field may be constant for a time in some examples and / or may be pulsed. The pulses of the electric field may have any of a variety of shapes (e.g., square pulses, triangular pulses, sinusoidal pulses, impulse pulses, and / or exponential decay pulses). Electrolysis may be performed to generate products of electrolysis. Electrolysis products may be generated, for example, from ions and molecules of an aqueous solution. The aqueous solution may be the native physiological concentration solution present in the tissue. The ionic composition of bodily fluids may be used as an ionic conductive media to cause the electrochemical reaction forming the basis of electrolysis and / or may be introduced to (e.g., injected into) the tissue during methods described herein. Electrolysis products may be generated by passing a current through tissue using electrodes described herein, such as electrodes 16 of FIG. IB. The electrolysis products may diffuse in the tissue and may ablate permeabilized cells. The time duration during which electrolysis is performed and / or the quantity of electrolysis products is generated may be set herein such that the electrolysis products cause ablation of permeabilized cells, but not ablation of non-permeabilized cells. Moreover, the time duration and / or quantity of electrolysis products may be set such that the extracellular matrix of the permeabilized cells remains intact, which may facilitate regeneration in the region of the ablated tissue.

[0098] Any of a variety of tissue may be treated using systems and examples described herein. Generally, tissue of an endoluminal organ may be treated where tissue regeneration is desirable or where it is desirable to replace one type of cells with another using the systems. Examples include intestine, duodenum, stomach, bladder, uterus, endometrial lining, endobronchial lining, ovaries, colon, rectum, sinuses, ducts, ureters, prostate, skin, muscle, nerve, diaphragm, kidney, follicles, brain, lymphatic vessels, blood vessels, breast, esophagus, lung, liver, kidney, lymph nodes, lymph node basins, and / or heart. Generally, any endoluminal structure may be treated using systems, devices, and techniques described herein. Replacement of one type of tissue with another may be in fibrotic areas where it is desired to replace fibrotic cells with stem cells that can remodulate the area or when pancreatic islets are injected in part of the liver to generate new sources of insulin. Other tissue may be treated in other examples.

[0099] FIG. 2 is a schematic diagram of a ablation device 200 including an imaging device 28 according to examples described herein. In some examples, the ablation device 200 may be the ablation device 120 of FIGS. 1A and IB. In some examples, the imaging device 28 may be the imaging device 18 that trails the ablation device 200.

[0100] The ablation device 200 may include one or more expandable members 24, one or more electrodes 262, and an elongate flexible device 22. In some examples, the elongate flexible device 22 may be the elongate flexible device 130 of FIGS. 1 A and IB. The elongate flexible device 22 may include an elongate member that has a tubular shape. A distal end of the elongate flexible device 22 may be introduced to tissue 10 of an endoluminal organ, such as an organ in a digestive path. The expandable members 24 are optional and may be omitted in some embodiments. In some implementations, the ablation device 200 may be an end effector for a flexible ablation instrument that extends through a working channel of the elongate flexible device 130 or along the elongate flexible device 130. In some implementations, the ablation device 200 may optionally be a removable attachment that is coupled to a distal end of the elongate flexible device 130.

[0101] The ablation device 200 may include one or more expandable members 24. In the illustrated embodiment, the one or more expandable members 24 may be balloons. Other expandable members may be used in other examples, such as meshes and the like. The one or more expandable members 24 may be expanded in a variety of different manners. In some embodiments, the one or more expandable members 24 may be inflated with a fluid, such as air, saline, a radiopaque solution, and the like. The fluid may be introduced to the one or more expandable members 24 through the elongate flexible device 22. The one or more expandable members 24 may have a length of 4 to 5 cm and may inflate to a diameter between 2 cm and 4 cm. However, the length and inflatable diameter of the expandable members 24 may vary depending on the tissue to be treated. In other examples, the expandable members 24 may be expanded in other ways (e.g., rolling, unfurling, pushing).

[0102] The ablation device 200 includes one or more electrodes 262 that provide electrolysis and electroporation treatment according to the embodiments of the present disclosure. The one or more electrodes 262 may be used to provide both electrolysis and electroporation to the targeted tissue. While a plurality of electrodes 262 are shown, in some examples, multiple pairs of electrodes, including an anode and a cathode, may be used. In some examples, one electrode, such as an anode or a cathode, may be used in conjunction with a return electrode (e.g., in a unipolar configuration). In some examples, the electrodes may be positioned and / or spaced to create and / or promote a uniform electric field. In some examples, one or moreelectrodes may be physically connected to one or more other electrodes (e.g., using a web or other portion of connecting material) to create a fixed spacing between the electrodes. In the illustrated embodiment, the plurality of electrodes 262 may be disposed on a surface of the expandable member 24 to provide an ablation circumferentially. In some embodiments, the plurality of electrodes 262 have a round cross-section. The plurality of electrodes 262 may be alternated between an anode and a cathode arrangement. The anodes and cathodes of the plurality of electrodes 262 may be separated by dielectrics at any point where they intersect.

[0103] The anodes and cathodes may be fabricated from any conductive materials such as stainless steel, titanium, gold, copper, graphene, graphite, and the like. Generally, electrode materials may be selected based in part on the application. For example, the electrode material may be chosen to minimize transferring ions from the electrode material to the target tissue. For example, steel may be less preferred. Titanium and gold may have some degree of participation in the electrolysis process; however, they may not generate a toxic residue and may be used in some examples. In some examples, titanium may be used and may be preferred. In some examples, stainless steel may be used. In some examples, two separate metals such as zinc and aluminum may be used that when left in close proximity produce a current and thus may generate electrolysis products. In some examples, the spacing between adjacent electrodes 262 may be around 3 mm in some examples, although other spacings may be used.

[0104] In some examples, a user may move the ablation device 200 and the imaging device 28 in a manner that the imaging device 28 may trail the ablation device 200. The user may observe a white ring or line on a treated region immediately after ablation by viewing a realtime image from the imaging device 28. The user may move the ablation device 200 in a manner that at least one of the anodes may be positioned in proximity to an undertreated region or a region to be marked by ablation.

[0105] In some examples, a user may move the ablation device 200 and the imaging device 28 to mark a leading edge and / or a trailing edge of a zone for treatment using the ablation device 200 as described herein. After marking the leading and / or trailing edges, the user may move the ablation device 200 to perform ablation based on the marked leading and / or trailing edges (such as between the edges when both are present, or past one edge for a desired length or towards a desired landmark where one edge is present).

[0106] The one or more electrodes 262 may be attached to two or more wires that run along the elongate member of the elongate flexible device 22 that provide electrical signals, suchas voltages and / or currents to the one or more electrodes 262. These two wires run down the length of the elongate member to the controller 104 and / or power supply 102 generator, which may be outside the body. Once the one or more expandable members 24 have been positioned in place and inflated to the expandable configuration with the one or more expandable members 24 compressing themselves onto the gastrointestinal wall, a current is run through the electrode, causing an electrolysis and electroporation field. The applied electric field can be between 10 V / cm and 2,500 V / cm. The one or more expandable members 24 may then be deflated.

[0107] For example, one or more electrodes 262 may be made of a piezoelectric and / or thermoelectric material that may generate power over time. In some examples, a power source may be placed in the tissue, such as a battery. In some examples, a microbattery may be used that may include one or more of the electrodes described herein, or other electrodes. The microbattery may in some examples be charged using micro currents in the tissue (e.g., bodily microcurrents). For example, a stent may be used having such a microbattery.

[0108] In some examples, the ablation device 200 may be used or coupled with the imaging device 28 in a manner that the imaging device 28 may trail the ablation device 200. In some examples, the user may observe a white ring or line on a treated region immediately after ablation by viewing a real-time image from the imaging device 28, and the user may move the ablation device 200 (e.g., manually or under robotic guidance such as via operator input system 1106) in a manner that at least one of the anodes may be positioned in proximity to an undertreated region or a region marked for ablation. Alternatively, a computing device, such as the processor 106 or an external computing device coupled to the controller 104 of FIG. 1 A may perform visualization of the zone using image recognition, etc., based on images from the imaging device 28, and autonomously actuate the ablation device 200 to the region of ablation to allow for better precision to avoid treatment gaps or overlapping zones of ablation, or provide guidance to a user for user positioning of the ablation device 200.

[0109] In some examples, a user may move the ablation device 200 to mark a leading edge and / or a trailing edge of a zone for treatment using the ablation device 200 to cause energy delivery. After marking the leading and / or trailing edges as markers, the user may move the ablation device 200 to perform ablation based on the leading and / or trailing edges. In some examples, the computing device may mark a leading edge and / or a trailing edge of a zone for treatment using the ablation device 200. The computing device may further control the imaging device to move to the leading edge and image a zone and identify either a landmark or an electrolysis marker in the zone based on images from the imaging device; move theimaging device to a proximal portion of a treatment zone to measure a travel distance from the trailing edge to either the landmark or the electrolysis marker; move the imaging device to the leading edge, pre-plot a map including the zone, plan one or more treatment segments in the map based on a predetermined length in the treatment zone, a treatment location, the travel distance or combinations thereof; and move the ablation device to the one or more planned treatment segments. Thus, by including the imaging device 28 in the ablation device 200, automated treatment may be performed.

[0110] FIG. 3 is a flow chart of a method 300 for medical procedure visualization using the system 100 of FIG. 1A. The method 300 may begin in operation 302 and an ablation device, such as the electrode member 15 of the medical procedure visualization system 100, may treat tissue within a treatment zone using endoluminal ablation by the ablation device. In some examples, the ablation includes a combination of electroporation and electrolysis that may cause a change in coloration of the tissue. The method 300 may proceed to operation 304 and a processor, such as a processor 106 in the controller 104 or an external computing device coupled to the controller 104, controls an imaging device, such as the imaging device 18 to image the zone to identify treated regions within the zone. In some embodiments, such imaging control may be performed manually by a user (e.g., via manual movement or under robotic guidance such as via operator input system 1106). In some embodiments, the processor may autonomously perform the imaging. The imaging may be performed using white light endoscopy, NBI, fluorescence, chromoendoscopy, OCT or radial ultrasound or a combination thereof. In some embodiments, the white light endoscopy may be used to image the zone and the treated regions appear discolored (e.g., white). The white light endoscopy may be useful for real-time confirmation of treated regions in the zone because of the relatively instantaneous appearance of discolored treated regions in post-ablation images. For example, tissue whitening may be a component of a visual change (e.g., discoloration) that occurs during treatment. In some examples, an overall change in discoloration of the tissue as a whole may occur, and the eye is able to sense the discoloration in the white light spectrum. In some examples, blue light optical filters may be used to view the tissue, and the change in discoloration may be visible in a more salient manner through the blue light optical filter.[OHl] The method 300 may proceed to operation 306 and the ablated portions within the region may be identified in the post-ablation images. In some examples, the user may manually identify the ablated portions. In some examples, the processor may perform image recognition to identify the ablated portions. Once the ablated portion in the zone is identified, one or more untreated or undertreated regions in the zone may be identified. In someexamples, a degree of the endoluminal ablation at the treated regions may be determined by visual evaluation by the user or image recognition by the processor. Once the degree of the endoluminal ablation is determined, additional ablation may be performed at selected additional regions within the target region. Such additional ablation may be used to provide treatment for untreated or under treated target regions. The energy applied for additional endoluminal ablation at the target region may be adjusted based on the degree of the endoluminal ablation. In some embodiments, adjusting the energy applied for additional ablation may include controlling at least one of pulse duration, a current applied, a charge applied (e.g., field strength), a voltage applied, a number of pulses, or a combination thereof. Optionally, in some examples, medication may be delivered to the treatment regions, including providing a pharmaceutical substance to or near the treatment regions.

[0112] The method 300 may proceed to operation 308 and additional endoluminal ablation may be performed at selected additional regions within the zone based on a location of the treated regions. In some embodiments, the additional ablation may be delivered to the zone based on an appearance of the treated regions. The zone may include the one or more untreated or undertreated regions. In some embodiments, the untreated or undertreated regions may be tagged in the post-ablation images, by tagging portions of images outside the treated regions in the zone. In some embodiments, such tagging may be performed by image recognition. In some embodiments, tagging in the post-ablation images may be compared with kinematic data from a robotic system that controls actuation of the ablation device 120. Based on the comparison, position data for the additional regions may be generated. The additional endoluminal ablation may be performed using the position data to position the robotic system to treat the selected additional regions.

[0113] The operations of the method 300 may be executed in an order other than as shown. The operations of the method 300 may include further operations. In some examples, identification of the zone may be performed prior to the method 300. For example, a leading edge and / or a trailing edge of the zone may be marked using the endoluminal ablation device in the method 300. In some embodiments, the leading edge and / or the trailing edge may be visualized under white light endoscopy in a manner that ablation may be performed immediately after marking the edges. The ablation may be performed by manually, under robotic assistance, or autonomously moving the ablation device 120 to place electrodes in proximity to undertreated or untreated regions and apply treatment, until there is no skipped lesion found between the leading edge and the trailing edge.

[0114] FIG. 4 is a flow chart of a method 400 of medical procedure visualization using the medical procedure visualization system 100 of FIG. 1A. The method 400 may begin in operation 402 and an ablation device, such as the electrode member 15 of the medical procedure visualization system 100, may treat tissue within a zone of a target region using endoluminal ablation by the ablation device, including a combination of electroporation and electrolysis. The electroporation and electrolysis treatment may cause coloration of the tissue. The method 400 may proceed to operation 404 and a processor, such as a processor 106 in the controller 104 or an external computing device coupled to the controller 104, controls an imaging device, such as the imaging device 18 to image the zone to identify treated regions within the zone. In some embodiments, such imaging control may be performed manually by a user or under robotic guidance such as via operator input system 1106. In some embodiments, the processor may autonomously perform the imaging. The imaging may be performed using white light endoscopy, NBI, fluorescence, chromoendoscopy, OCT or radial ultrasound or a combination thereof. In some embodiments, the white light endoscopy may be used to image the zone and the treated regions appear discolored (e.g., white). The white light endoscopy may be useful for real-time confirmation of treated regions in the zone because of the relatively instantaneous appearance of discolored treated regions in postablation images.

[0115] The method 400 may proceed to operation 406 and the ablated portions within the region may be identified in the post-ablation images. In some examples, the user may manually identify the ablated portions. In some examples, the processor may perform image recognition to identify the ablated portions. In some examples, whether the treated regions are different from at least one untreated region in appearance may be determined to identify the ablated portions using image recognition, kinematic data, shape sensing data and / or visual evaluation. In some examples, a degree of ablation at the treated regions may be determined by image recognition, kinematic data, shape sensing data and / or visual evaluation. The operations of the method 400 may be executed in an order other than as shown.

[0116] The operations of the method 400 may include further operations for pre-operative planning. In some examples, identification of the zone may be performed using the method 400. For example, prior to performing full ablation in the target zone, a leading edge and a trailing edge of the zone may be marked by the ablation device. As described above, the ablation device may deliver energy (such as electrolysis with or without electroporation) or other marking at doses and amounts of time sufficient to allow coloring of a region to provide physical markers to tissue but without causing complete ablation of the tissue for treatment.In some embodiments, the leading edge and / or the trailing edge may be visualized by imaging using white light endoscopy and NBI for planning purposes. The leading, trailing, and / or overlapping edges may be compared with at least one of shape sensing data, kinematic data, or positional data. Based on the comparison, a treatment plan may be generated and an ablation device may be positioned between the leading and trailing edges based on the at least one of shape sensing data, kinematic data, or positional data to perform the ablation. In some embodiments, the ablation device may be positioned in a manner that an electrode, such as a the most distal electrode, of the electrodes 16 of the electrode member 15 may be positioned at the leading edge to mark the leading edge. An electrode, such as the most proximal electrode, of the electrodes 16 of the electrode member 15 may be positioned at the trailing edge to mark the trailing edge. Depending on the overall desired treatment length, the leading and trailing edges may be marked at the same time / location or marked at different times / locations by moving the electrode member 15 between positions. The other electrodes, including anodes and cathodes may be positioned between the leading and trailing edges during marking.

[0117] In some examples, the imaging device, such as the imaging device 18 of FIG. IB may be controlled to move to the leading edge and image a zone. The processor may identify either a landmark or one or more markers in the form of electrolysis shapes, for example, circle, square, dot, hexagon, trapezoid, custom shape, etc., or any combination thereof, in the zone based on images from the imaging device, and further control to move the imaging device to a proximal portion of a treatment zone (e.g., a lumen or cavity length) to measure a travel distance from the trailing edge to either the landmark or the electrolysis marker, and further control the imaging device to move to the leading edge. The processor may pre-plot a map including the zone, and plan one or more treatment segments in the map based on a predetermined length in the treatment zone, a treatment location, the travel distance or combinations thereof. In some embodiments, the pre-plotting of the map includes anatomical positioning. In the medical procedure according to the pre-plotted map, the processor may move the ablation device to the one or more planned treatment segments. During the medical procedure, the processor may dynamically adjust one or more locations of the one or more treatment segments based on the images to update the planned one or more treatment segments. Thus, automated pre-operation planning and automated treatment may be performed. In some examples, the automated pre-operation planning and automated treatment may be based on a reference of lineal travel that provides anatomical positioning for mapping, planning, confirmation and dynamically adjusting and updating. The reference of lineal travelmay be obtained by some computer vision algorithms. In some examples, anatomical positioning, such as identification of landmarks may use a YOLO neural network or an attention network. For example, highlighting a region as a landmark in an image may readily indicate the relation between the image and the region in the actual tissue. Following a landmark classification, the processor may determine the corresponding depth values related to the relevant portion of the image or the entire image identified, e.g., by the YOLO network, and mark the corresponding portions of the tissue that represent the positional relationship between the region and the markers or the map. In some examples, Visual SLAM or other computer vision algorithms that may calculate a position and orientation of an imaging device with respect to its surroundings including the tissue may be used for anatomical positioning.

[0118] In some examples, computer vision algorithms may be used to create a mosaic or composite view of an anatomical zone for treatment. The imaging device may be controlled to take a series of images of a treatment zone and a mosaic algorithm can stitch together several images to form a composite view of the treatment zone. The composite view can be taken at various stages of the procedure and the composite view may be generated or updated more than once before, during, or after the procedure. For example, the composite view can be generated prior to treatment for pre-planning. This may be part of an initial scan of a target region as described herein. Areas desired for marking and / or treatment can be identified in the pre-planning composite view. After a composite view is created, a user may then optionally perform marking on tissue using the ablation device as described herein. In some embodiments, marking may be omitted. Then, ablation may be performed using the ablation device. Marking and / or ablation may be performed manually under visualization, under robotic assistance, or autonomously as described herein. The composite view may optionally be displayed concurrently with the marking and / or ablation steps and the composite view may be updated based on the position and orientation of the ablation device relative to the anatomy. Subsequent to treatment, treated tissue can be identified by a color change as described herein. A further composite view may be optionally generated or updated to depict the amount of treated tissue. Additional treatment may be performed as described herein and a further composite view may be generated or updated based on the additional treatment. Further details of image mosaicking is found in U.S. Patent No. 10,695,136, which is incorporated herein by reference.

[0119] In some examples, imaging may be assisted by introducing a frame of reference for imaging. For example, an ablation device or a catheter with cm or mm markings. Thus, the image may include a known reference scale that may be used as a registration marker tomeasure movement of the ablation device including the electrode member. Based on the images including the scale, movement of the ablation device in a treatment zone, such as lumen or cavity, may be visualized as a length.

[0120] In some embodiments, an initial scan of a target region may be performed by imaging using the imaging device to survey the target region. Proximal and distal markers may be set to indicate the region of desired ablation. The markers may be set virtually in the images from a user interface, or the markers may be set as leading and / or trailing edges provided by the ablation device (e.g., electroporation and electrolysis energy application or other marking caused by the ablation device). Ablation for treatment may then be performed either manually where a user applies ablation based on the visual feedback, or via a user input device under robotically assisted guidance, or fully automatically where a processor controls treatment using the markers as start and stop locations, or semi-automatically where the processor may use a marker as a start position and an input by the user for a desired treatment length, or the user may select a start location without a specific marker applied and the processor may perform ablation -imaging loop until the system reaches the stop marker, etc. After the treatment has been applied, a post-treatment scan by imaging may be performed to identify any gaps or undertreated regions, which can then be retreated either manually or automatically using the system.

[0121] In some examples, training algorithms and software to be executed by the processor 106 or the external computing device to treat regions of disease may be performed using Al and / or ML. For example, creating a model for the target disease may include training a model of Al and / or ML, such as SLAM and / or YOLO, or may use images of treated regions with positional and / or kinetic data or any clinical data related to a target disease for treatment from a pool of patients. Planning ablation treatment by the trained program or algorithm with the model may use the images with positional and / or kinetic data or any clinical data from a target patient. Thus, positioning the ablation device 120 in a zone for treatment may be performed using the medical procedure visualization system 100.

[0122] Examples described herein, including methods described with reference to FIG. 3 and FIG. 4 may refer to treating tissue within a zone and imaging the zone. However, it is to be understood that in some examples, treating the tissue may refer simply to marking the tissue, without necessarily providing ablation or significant ablation. Controllers described herein may provide one or more pulses or other waveforms to electrodes disposed proximate tissue, where the pulse magnitude, count, and / or duration are set to mark the tissue. For example, the tissue may turn discolored responsive to production of certain species at theelectrodes. The marking of the tissue may occur in some examples under conditions which may not cause ablation of a volume of tissue, or significant ablation of tissue. In some examples, tissue marking using electrodes as described herein may be performed by using electrolysis alone and / or primarily electrolysis. In some examples, such tissue marking may be used with application of subsequent voltage and / or current pulses to further cause ablation.

[0123] Accordingly, in some examples, one or more electrodes may be activated to mark tissue, either together with or separate from significant tissue ablation. For example, in block 302 of FIG. 3 and / or block 402 of FIG. 4, tissue may be marked. Imaging the tissue (such as in block 304 of FIG. 3 and / or block 404 of FIG. 4) may accordingly allow the markings to be visualized (either by a human user and / or an automated image analysis system). Tissue treatment may then be performed where the location of ablation is determined based on a location of the markings. The tissue treatment may include ablation.

[0124] Accordingly, control systems (e.g., controllers) described herein may provide a first set of waveforms to electrodes, wherein the first set of waveforms provide energy to the tissue sufficient to mark the tissue. Based on a location of the visualized markings, the electrodes may be positioned at a treatment area, and the control system may provide a second set of waveforms to the electrodes, where the second set of waveforms provide energy to the tissue sufficient to ablate the tissue (e.g., using electroporation and electrolysis).

[0125] Additionally, it is to be understood that the size, shape, and positioning of electrodes may vary. While FIG. IB and FIG. 2 depict electrodes which may be proximate a full circumference of tissue (e.g., gastrointestinal tissue), in some examples, only a portion of a circumference of tissue may be treated and / or marked. For example, an electrode may be sized and / or positioned to be proximate only a portion of a circumference of the tissue. In some examples, after marking and / or treating a portion of the circumference, the device may be rotated to place the electrodes proximate an untreated or unmarked portion of the circumference, and the untreated or unmarked portion may be treated and / or marked.

[0126] FIG. 5 is a schematic diagram of anatomy arranged in accordance with examples described herein. The anatomy includes a liver 502, stomach 504, pancreas 506, duodenum 508, and jejunum 510. Examples of ablation devices described herein may deliver electric fields, and therefore electroporation and electrolysis, to the duodenum 508 and / or jejunum 510.

[0127] FIG. 6A is a schematic diagram of an electrode as an anode according to examples described herein. FIG. 6B is a schematic diagram of an electrode as a cathode according to examples described herein.

[0128] Responsive to delivery of charge waveform in the duodenum 508 and contact with aqueous secretions in the lining, destructive acidic hydrogen ion species are being prominently generated at the anode while destructive alkaline hydroxide species are being generated at the cathode. In some examples, water reaction of anode produces oxygen gases, acidic hydrogen ions and electrons. Sodium chloride reaction of anode produces chlorine gas that attacks carbon and electrons. Localization of chlorine and chloride ions to the anode may result in production of known decoloring chemicals such as the chlorite ion (CICh ) and / or other species such as sodium hypochlorite (NaOCl). In some examples, water reaction at cathode produces hydrogen gases and basic hydroxide ions. Sodium reaction of cathode may produce solid sodium in extremely small quantities. As ionic species interact, acidic species, such as hydrochloric acid (HC1), are produced at the anode and alkaline species, such as sodium hydroxide (NaOH), are then produced at the cathode. These products from the anode and cathode may be used to discolor the tissue without notable injury, or in some examples as described herein, can be used alongside electroporation to further contribute to the mucosal ablation in the region of the electroporated cells. In some embodiments, electrolytic products may be used both in the tissue coloration process as well as to perpetuate electroporation- mediated ablation of tissue.

[0129] When electrodes may pass current through tissue in contact with or in proximity to the electrodes, anodes and cathodes of the electrodes may generate acidic and basic substances, respectively. The substances may leach into the tissue and may cause discoloration (e.g., whitening) of the tissue. Initially, anodes may provide prominent discoloration. Over time, relatively uniform ablation may be observed in proximity to both anodes and cathodes. In some embodiments, the amount of discoloration substances produced may be controlled as a function of charge density to control the ablation. Charge density can be tuned through control of end-effector size, current delivery, capacitance, duration or number of pulses, or other generator-controlled parameters. In this manner, endoluminal ablation described herein may produce a change in color of treated tissue. This change in color may be used, as described herein, to adjust and / or plan treatment. In some examples, the color change may occur to a different degree at locations corresponding to electrode locations and / or particular electrode locations. Accordingly, planning treatment and / oradjusting treatment herein may refer to the positioning of the treatment device to position electrodes in particular places based on the imaging.

[0130] FIG. 7A is an example image 70 of a medical procedure for visualizing a treatment site with an ablation device 72 according to examples described herein. The ablation device 72 may include one or more expandable members 74 and an ablation device including one or more electrodes 76. In some examples, the ablation device 72 may be the ablation device 120.

[0131] The ablation device 72 may be introduced to a small intestine of a patient, while an expandable member 74, such as the expandable member74, aids with expanding a flexible electrode member having a plurality of electrodes 76 for contacting target tissue. Once the ablation device 72 reaches a target treatment site and the expandable member 74 and the electrodes 76 have been expanded into tissue contact, ablation using electroporation and / or electrolysis is performed at desired treatment locations. Following treatment, the expandable member 74 and the electrodes 86 may be compressed. An imaging device (not shown) of the elongate flexible device (e.g., a monoscopic or stereoscopic camera on an endoscope), such as the imaging device 18 may image the treatment site. The imaging may be performed immediately following the ablation.

[0132] FIG. 7B is an example image 70 of a medical procedure for visualizing a treatment site with a ablation device 72 according to examples described herein. Once tissue within a zone is treated using an ablation device including electrodes 76, such as the electrode member 15 of the ablation device 120, white rings 702 and 704 appear immediately on treated regions of the tissue as traces of ablation. The imaging device may image the zone using gross visualization, such as white light endoscopic monoscopic visualization. The treated regions may be identified by recognizing the white rings 702 and 704. In some examples, the white rings 702 of the treated regions over electrodes that perform as anodes have whiter and more prominent colorations than the white rings 704 of treated regions over electrodes that perform as cathodes immediately after the ablation. In some examples, the white rings 704 of the treated regions over the electrodes that perform as cathodes have redder and fainter colorations than the white rings 702 of the treated regions over the electrodes that perform as anodes immediately after the ablation. After a few hours from the ablation, the rings 702 and 704 of the treated regions change their colorations to red with equal prominence.

[0133] EXAMPLES

[0134] A duodenum 508 and distal jejunum 510 were chosen as models to demonstrate the ability of a medical procedure visualization system 100 to visualize a zone of ablation toidentify treated regions. The examples are provided to show examples of parameters of electroporation in combination with electrolysis that allow visualization of treated regions and to show that electroporation and electrolysis may be delivered precisely.

[0135] Minimally invasive ablation using electrolytic electroporation (reversible electroporation and electrolysis) was performed in the duodenum and jejunum mucosa as an example for the controlled use of electrolytic electroporation for a mode of ablation that facilitates the colorations of the ablated tissue.

[0136] The goal of the examples was to verify that electrolytic electroporation can ablate a region of tissue within a zone to identify an area and degree of the electrolytic electroporation ablation. To explore these aspects of electrolytic electroporation ablation, the duodenum mucosa and distal jejunum mucosa in one or more pigs were used as experimental models.

[0137] A series of acute studies were performed to evaluate the ability of the electrolytic electroporation technology to ablate to cause coloration of tissue, and to study the effect of various treatment parameters on the extent of coloration of tissue caused by the ablation. The outcome of this treatment was followed with histology taken six to eight hours after the ablation treatment, to verify that tissue ablated with electrolytic electroporation has the ability to regenerate.

[0138] EXAMPLE 1

[0139] Treatment sites were located in the duodenum 508. FIG. 8A includes example images of treatment sites using white light endoscopy, in accordance with examples described herein. A ring 802 of ablation corresponding to an anode was more visually prominent than a ring 804 of ablation corresponding to a cathode. Thus, the rings may indicate treatment information, such as an actual treated region in the treatment zone, as well as a type of electrode that ablated the treated region, whether it is an anode or a cathode. These types of information may be helpful in identifying exact locations of electrodes and corresponding treated regions as well as planning additional ablation.

[0140] The “white” rings of ablation then become red over time, and the ablation regions directly over the electrodes have the noticeable red appearance of the ablation at one hour post ablation. FIG. 8B is an example image of a treatment site using NBI, in accordance with examples described herein. The treatment site is located in the duodenum 508. Rings 806 showing the regions were then further grossly visualized using NBI as well, with the ablations directly over the electrodes being more prominent in NBI mode.

[0141] Using the images of white light endoscopy and NBI, a user or a robotic system may map surface area of treatment zones with confidence of where to start and end a new treatment zone in order to ablate as much duodenopathy as possible given the dose dependent relationship with ablation and A1C reduction known to occur with DMR using thermal approaches.

[0142] At six to eight hours after tissue is explanted and analyzed, histology of the sites of electrodes (cathode and anodes) having mucosal eruption zones indicative of complete ablation and cellular apoptosis (trans-mucosal ablation) may be obtained. FIG. 8C is an example image of a treatment site with histology showing regions of mucosal eruption correlating to electrode placement in accordance with examples described herein. Alkaline injuries are known to be more caustic, for example due to the alkaline species that occurs in esophageal injuries. The higher surface tension of alkalis allowing a longer contact time with esophageal tissues explains the more severe damage to the esophagus. Caustic injuries result in coagulative or liquefactive necrosis, loss of both intracellular and extracellular architecture, e.g., ablation of the extracellular matrix, and in high concentrations can lead to damage to the underlying muscle leading to scarring, stricture and, in worst case scenarios, perforation. Severe caustic injuries due to highly concentrated areas of contact in sensitive organs are thus very devastating and not desirable. During E2 ablation, moderate, transient ionic species and caustic byproducts were produced from the charge generated at the electrode surface. Thus, the generated ionic species generated from the electrolysis may diffuse into the intracellular region of the cell and cause cellular apoptosis where electroporation (poration of cells) has occurred within the electric field applied focally to the targeted region allowing for controlled ablation depth, without noticeable damage to the extracellular matrix, as seen in the histological example provided. Thus, death can be caused to cells within the targeted region of electroporation without damage to the surrounding extracellular matrix. By visualizing the treatment site, ablation depth may be controlled to preserve the extracellular scaffolding that enables more rapid tissue regeneration without scarring, fibrosis, stricture or ulceration, and with protection of the underlying muscle in the bowel wall. In the case of DMR or endobronchial ablation to treat chronic bronchitis, it is preferable to tune the energy such that complete cellular ablation is achieved with minimal / no damage to the ECM. In some applications, however, it may be desirable to generate sufficient charge to damage the ECM intentionally through caustic and acidic processes. For instance, when using E2 to generate ablation of nerves or to coagulate vasculature intentionally (or various other examples), it may be desirable to locally disrupt ECM components in addition to ablating cells bygenerating an excessive amount of products of electrolysis that would cause an ablation effect locally independent of the field applied to the targeted region. In these cases, the ablative energy can be adjusted to provide a higher local amount of charge to generate higher concentrations of caustic and / or acidic products that denature proteins in the targeted area using electrolysis alone.

[0143] White light visualization of the treatment regions of ablation are grossly visible under direct vision within a relatively short period from ablation. NBI images of the treatment regions become more visually noticeable as time passes. While light is useful for confirmation of ablation, apposition, and successful treatment within a relatively short period from ablation, NBI markedly improves capillary pattern contrast and is an in vivo method for visualizing microvessel morphological changes in the mucosal tissue. Thus, NBI allows a better evaluation of mucosal and vascular patterns. The vascular lock occurs post ablation where the electroporation field is applied. NBI is hypothesized to define the ablation regions more readily and provide more drastic appearance of the lesions as a filter. Further, other modalities like fluorescence, chromoendoscopy, OCT or radial ultrasound may be used to visualize and confirm ablation regions. In some examples, monoscopic view with direct visualization lends itself to surface area mapping while stereoscopic view could provide more robust and accurate surface area mapping of treatment zones and potentially volumetric measurements of total areas of ablation. The OCT and radial ultrasound may identify the ablation zones and provide volumetric ablation along with corresponding areas of depth. In some examples, Al and ML neural networks and identifiers, such as SLAM and / or YOLO, could be utilized to train both monoscopic and stereoscopic video and images to overlay exactly where ablation has occurred, track the zone and compute ablation information, such as total area and / or volume of treatment and provide a user the video and / or images with the overlay of ablation regions, the zone tracking, and the computed ablation information. In some embodiments, Al and ML may also be utilized to map the entire area of duodenopathy, track ablation regions and thus provide the user a “tracking / progress bar” correlating to the total area and / or volume of treatment applied to ensure the most efficacy and safety possible for the DMRe therapy.

[0144] In Examples 2 and 3, an ablation device with a full-size DMR catheter with circumferential electrode traces was used.

[0145] EXAMPLE 2

[0146] Treatment sites were located in the distal jejunum 510. In this example, ablation was applied by discharge of a capacitance at a voltage 300 V, the capacitance of 400 pF, and a quantity of charge per surface area (Q / SA) of 3.37xl0'4C / mm2. An electric field strength can be computed for the voltage 300 V provided across a gap of 3 mm. A balloon has a diameter of 29 mm and a length of 40 mm. The balloon is given a pressure of 2.5 pound-force per square inch (psi).

[0147] FIGS. 9A-9C are example images of a treatment site of a small intestine of a pig after ablation using white light endoscopy according to examples described herein. FIG. 9A illustrates the appearance four minutes after the treatment. FIG. 9B illustrates the appearance seven minutes after the treatment. FIG. 9C illustrates the appearance 160 minutes after the treatment.

[0148] At four minutes after the treatment, very faint partial circumferential white lines 902 corresponding to anode electrodes were observed as shown in FIG. 9A. Three minutes later, the white lines 902 became more noticeable in FIG. 9B, compared to the white lines 902 in FIG. 9A. The white lines 902 had disappeared by 160 minutes after the treatment as shown in FIG. 9C.

[0149] EXAMPLE 3

[0150] Treatment sites were located in the distal jejunum 510. In this example, ablation was applied by discharge of a capacitor at a voltage 300 V, the capacitance of 800 pF, and a Q / SA of 6.37xl0'4C / mm2. An electric field strength can be computed for the voltage 300 V provided across a gap of 3 mm. A balloon has a diameter of 29 mm and a length of 40 mm. The balloon is given a pressure of 2.5 psi.

[0151] FIGS. 10A-10D are example images of a treatment site of a small intestine of a pig after ablation using white light endoscopy according to examples described herein. FIG. 10A illustrates the appearance three minutes after treatment. FIG. 10B illustrates the appearance eight minutes after the treatment. FIG. 10C illustrates the appearance 45 minutes after the treatment. FIG. 10D illustrates the appearance 130 minutes after the treatment.

[0152] At three minutes after the treatment, distinct solid white lines 1002 corresponding to anode electrodes were observed as shown in FIG. 10A. The outer white line 1002 is broken at a top portion, and not fully circumferential to make a ring. At eight minutes after the treatment, subtle white lines 1004 corresponding to cathode electrodes were observed as shown in FIG. 10B. At 45 minutes after the treatment, the white lines 1002 and the white lines 1004 had the same level of whiteness. The white lines 1004 might have become moreprominent due to the ablation over time, between eight to 45 minutes. These white lines 1002 and 1004 are visible with a similar whiteness level in FIG. 10C. The white lines 1002 started having red coloration 1008 at their top left portion at around 160 minutes after the treatment as shown in FIG. 10D.

[0153] Based on the results of Examples 2 and 3, a rapid whitening effect was observed within three minutes from ablation at treatment regions corresponding to anode electrodes being acidic with low pH and having positive polarity leads. A delayed whitening effect was observed from three to ten minutes from the ablation at treatment regions corresponding to cathode electrodes being basic with high pH and having negative polarity leads. Over time, after about 45 minutes post ablation, all the treated regions began to show a similar level of whitening. After two to six hours, coloration changes from a whiter color to a deep red color were observed. The comparison results of Examples 2 and 3 show that the whitening effect may be titrated with charge. For example, applying lower charge as shown in Example 2 results in less whitening and applying higher charge as shown in Example 3 results in more whitening with the same electric field strength.

[0154] From the examples above, colorations for visualization may be controlled by, for example, positioning of anode / cathode electrodes, a lapse of time post ablation, dosage of ablation controlled either electrically or chemically, and / or imaging techniques. The white coloration of treated regions may occur instantaneously after ablation. Over time, around one hour to several hours, red coloration develops.

[0155] In some examples, charges applied to a zone of treatment may be optimized based on patterns. In some examples, the zone may be divided into portions of the circumference, such as quadrants or trios. The charges may be applied to ablate undertreated regions of the circumferential zone that matches to the divided zone, to improve apposition of treatment. For example, ablating on a corner of an endoluminal organ may fail due to lack of full contact with a portion of electrodes. In some examples, the medical procedure visualization system 100 may detect such failure and inform a user to retreat or automatically retreat the undertreated regions by moving the electrodes in proximity to the undertreated regions and perform additional ablation. In some examples, the medical procedure visualization system 100 may detect such failure and change active portions of the electrodes to retreat the undertreated regions. In some examples, a width of white ring may be broadened by activating a wider area of electrodes. In some examples, prominence of the white or red rings may be adjusted by adjusting a voltage, an electric field, capacitance, a current amplitude, a duration, a number of pulses per time, etc. In some examples, the medical procedure visualizationsystem 100 may detect prominence of the white or red rings, and adjust dosage. In some examples, approximately 10 pulses may be applied in each zone. In other examples, a fewer number (e.g., five) of initial pulses may be applied and the medical procedure visualization system 100 may check the prominence of white lines, and determine whether to apply further pulses at regions between electrodes or outside an area in contact with the electrodes or at the same regions to optimize a bleaching effect.

[0156] In some examples, the medical procedure visualization system 100 may also inform treatment and / or medication dosing. In some examples, a bowel may become motile during / under treatment. The medical procedure visualization system 100 may inform an amount of muscle paralytics and / or anti-motility agents based on observed movement, thus real-time delivery of medication may be performed.

[0157] Aspects of this disclosure herein can be part of a computer-assisted teleoperational manipulator system, sometimes referred to as a robotically-assisted manipulator system or a robotic system. The manipulator system can include one or more manipulators that can be operated with the assistance of an electronic controller (e.g., computer) to move and control functions of one or more instruments when coupled to the manipulators.

[0158] FIG. 11 illustrates an embodiment of a robotically-assisted manipulator system for use with the systems described herein (also referred to as a robotically-assisted servomechanism system). The manipulator system can be used, for example, in surgical, diagnostic, therapeutic, biopsy, or non-medical procedures, and is generally indicated by the reference numeral 1100. As shown in FIG. 11, a robotically-assisted servomechanism system 1100 can include one or more manipulator assemblies 1102 for operating one or more medical instrument systems 1104 in performing various procedures on a patient P positioned on a table T in a medical environment 1101. For example, the manipulator assembly 1102 can drive catheter or end effector motion, can apply treatment to target tissue, and / or can manipulate control members. For example, the manipulator assembly 1102 may drive one or more catheters as described herein and / or assist with positioning of portions of the system 100 of FIG. 1A. The manipulator assembly 1102 can be teleoperated, non-teleoperated, or a hybrid teleoperated and non-teleoperated assembly with select degrees of freedom of motion that can be motorized and / or teleoperated and select degrees of freedom of motion that can be nonmotorized and / or non-teleoperated. An operator input system 1106, which can be inside or outside of the medical environment 1101, generally includes one or more control devices for controlling manipulator assembly 1102. Manipulator assembly 1102 supports medical instrument system 1104 and can optionally include a plurality of actuators or motors that driveinputs on medical instrument system 1104 in response to commands from a control system 1112. The actuators can optionally include drive systems that when coupled to medical instrument system 1104 can advance medical instrument system 1104 into a naturally or surgically created anatomic orifice. Other drive systems can move the distal end of medical instrument system 1104 in multiple degrees of freedom, which can include three degrees of linear motion (e.g., linear motion along the X, Y, Z Cartesian axes) and three degrees of rotational motion (e.g., rotation about the X, Y, Z Cartesian axes). The manipulator assembly 1102 can support various other systems for irrigation, treatment, or other purposes. Such systems can include fluid systems (including, for example, reservoirs, heating / cooling elements, pumps, and valves), generators, lasers, interrogators, and ablation components.

[0159] Robotically-assisted servomechanism system 1100 also includes a display system 1110 for displaying an image or representation of the surgical site and medical instrument system 1104 generated by an imaging system 1109 which can include an imaging system, such as an endoscopic imaging system. Display system 1110 and operator input system 1106 can be oriented so an operator O can control medical instrument system 1104 and operator input system 1106 with the perception of telepresence. A graphical user interface can be displayable on the display system 1110 and / or a display system of an independent planning workstation.

[0160] In some examples, the endoscopic imaging system components of the imaging system 1109 can be integrally or removably coupled to medical instrument system 1104. However, in some examples, a separate imaging device, such as an endoscope, attached to a separate manipulator assembly can be used with medical instrument system 1104 to image the surgical site. The endoscopic imaging system 1109 can be implemented as hardware, firmware, software, or a combination thereof which interact with or are otherwise executed by one or more computer processors, which can include the processors of the control system 1112.

[0161] Robotically-assisted servomechanism system 1100 can also include a sensor system 1108. The sensor system 1108 can include a position / location sensor system (e.g., an actuator encoder or an electromagnetic (EM) sensor system) and / or a shape sensor system (e.g., an optical fiber shape sensor) for determining the position, orientation, speed, velocity, pose, and / or shape of the medical instrument system 1104. The sensor system 1108 can also include temperature, pressure, force, or contact sensors or the like.

[0162] Robotically-assisted servomechanism system 1100 can also include a control system 1112. Control system 1112 includes at least one memory 1116 and at least one computerprocessor 1114 for effecting control between medical instrument system 1104, operator input system 1106, sensor system 1108, and display system 1110. Control system 1112 also includes programmed instructions (e.g., a non-transitory machine-readable medium storing the instructions) to implement a procedure using the robotically-assisted servomechanism system including for navigation, steering, imaging, engagement feature deployment or retraction, applying treatment to target tissue (e.g., via the application of energy), or the like.

[0163] Control system 1112 can optionally further include a virtual visualization system to provide navigation assistance to operator O when controlling medical instrument system 1104 during an image-guided surgical procedure. Virtual navigation using the virtual visualization system can be based upon reference to an acquired pre-operative or intraoperative dataset of anatomic passageways. The virtual visualization system processes images of the surgical site imaged using imaging technology such as computerized tomography (CT), magnetic resonance imaging (MRI), fluoroscopy, thermography, ultrasound, OCT, thermal imaging, impedance imaging, laser imaging, nanotube X-ray imaging, and / or the like. The control system 1112 can use a pre-operative image to locate the target tissue (using vision imaging techniques and / or by receiving user input) and create a pre-operative plan, including an optimal first location for performing treatment. The pre-operative plan can include, for example, a planned size to expand an expandable device, a treatment duration, a treatment temperature, and / or multiple deployment locations.

[0164] FIG. 12A shows a medical instrument system 1200 according to some embodiments. In some embodiments, medical instrument system 1200 can be used in an image-guided medical procedure. In some examples, medical instrument system 1200 can be used for non- teleoperational exploratory procedures or in procedures involving traditional, manually operated medical instruments, such as endoscopy. In some embodiments, medical instrument system 1200 is interchangeable with, or a variation of, medical instrument system 1104 of FIG. 11. For example, the medical instrument system 1200 may include one or more catheters and / or endoscope as described herein and / or assist with positioning of portions of the system 100 of FIG. 1A.

[0165] Medical instrument system 1200 includes elongate flexible device 1202, such as a flexible catheter or endoscope (e.g., gastroscope, bronchoscope), coupled to a drive unit 1204. Elongate flexible device 1202 includes a flexible body 1216 having proximal end 1217 and distal end, or tip portion, 1218. In some embodiments, flexible body 1216 has an approximately 114-20 mm outer diameter. Other flexible body outer diameters can be larger or smaller. Flexible body 1216 can have an appropriate length to reach certain portions of theanatomy, such as the lungs, sinuses, throat, or the upper or lower gastrointestinal region, when flexible body 1216 is inserted into a patient’s oral or nasal cavity.

[0166] Medical instrument system 1200 optionally includes a tracking system 1230 for determining the position, orientation, speed, velocity, pose, and / or shape of distal end 1218 and / or of one or more segments 1224 along flexible body 1216 using one or more sensors and / or imaging devices. The entire length of flexible body 1216, between distal end 1218 and proximal end 1217, can be effectively divided into segments 1224. Tracking system 1230 can optionally be implemented as hardware, firmware, software or a combination thereof which interact with or are otherwise executed by one or more computer processors, which can include the processors of control system 1112 in Fig. 11.

[0167] Tracking system 1230 can optionally track distal end 1218 and / or one or more of the segments 1224 using a shape sensor 1222. In some embodiments, tracking system 1230 can optionally and / or additionally track distal end 1218 using a position sensor system 1220, such as an electromagnetic (EM) sensor system. In some examples, position sensor system 1220 can be configured and positioned to measure six degrees of freedom, e.g., three position coordinates X, Y, Z and three orientation angles indicating pitch, yaw, and roll of a base point, or five degrees of freedom, e.g., three position coordinates X, Y, Z and two orientation angles indicating pitch and yaw of a base point.

[0168] Flexible body 1216 includes one or more channels 1221 sized and shaped to receive one or more medical instruments 1226 (e.g., an ablation device 120 or an ablation device 200). In some embodiments, flexible body 1216 includes two channels 1221 for separate instruments 1226, however, a different number of channels 1221 can be provided. FIG. 12B is a simplified diagram of flexible body 1216 with medical instrument 1226 extended according to some embodiments. In some embodiments, medical instrument 1226 can be used for procedures and aspects of procedures, such as surgery, biopsy, ablation, mapping, imaging, illumination, irrigation, or suction. Medical instrument 1226 can be deployed through channel 1221 of flexible body 1216 and used at a target location within the anatomy. Medical instrument 1226 can include, for example, image capture devices, biopsy instruments, ablation instruments, catheters, laser ablation fibers, and / or other surgical, diagnostic, or therapeutic tools. Medical tools can include end effectors having a single working member such as a scalpel, a blunt blade, a lens, an optical fiber, an electrode, and / or the like. Other end effectors can include, for example, forceps, graspers, balloons, needles, scissors, clip appliers, and / or the like. Other end effectors can further include electrically activated end effectors such as electro surgical electrodes, transducers, sensors, imagingdevices and / or the like. Medical instrument 1226 can be advanced from the opening of channel 1221 to perform the procedure and then retracted back into the channel when the procedure is complete. Medical instrument 1226 can be removed from proximal end 1217 of flexible body 1216 or from another optional instrument port (not shown) along flexible body 1216. The medical instrument 1226 can be used with an image capture device (e.g., an endoscopic camera) also within the elongate flexible device 1202. Alternatively, the medical instrument 1226 can itself be the image capture device.

[0169] Medical instrument 1226 can additionally house cables, linkages, or other actuation controls (not shown) that extend between its proximal and distal ends to controllably bend the distal end of medical instrument 1226. Flexible body 1216 can also house cables, linkages, or other steering controls (not shown) that extend between drive unit 1204 and distal end 1218 to controllably bend distal end 1218 as shown, for example, by broken dashed line depictions 1219 of distal end 1218. In some examples, at least four cables are used to provide independent “up-down” steering to control a pitch motion of distal end 1218 and “left-right” steering to control a yaw motion of distal end 1218. In embodiments in which medical instrument system 1200 is actuated by a robotically-assisted assembly, drive unit 1204 can include drive inputs that removably couple to and receive power from drive elements, such as actuators, of the teleoperational assembly. In some embodiments, medical instrument system 1200 can include gripping features, manual actuators, or other components for manually controlling the motion of medical instrument system 1200. The information from tracking system 1230 can be sent to a navigation system 1232 where it is combined with information from visualization system 1231 and / or the preoperatively obtained models to provide the physician or other operator with real-time position information.

[0170] Other configurations of teleoperated manipulator systems are also contemplated, such as systems configured for multi-port or single-port procedures. For example, the embodiments described herein can be used with a da Vinci® Surgical System, such as the da Vinci X®, Xi®, or SP® Surgical Systems, all commercialized by Intuitive Surgical, Inc., of Sunnyvale, California.

[0171] FIG. 13 illustrates an example embodiment of a drive unit 1204 that can be used as part of the manipulator system 1100. The manipulator system 1300 includes a base 1320, a main column 1340, and a main boom 1360 connected to main column 1340. Manipulator system 1300 also includes a plurality of manipulator arms 1310, 1311, 1312, 1313, which are each connected to main boom 1360. The manipulator arms 1310, 1311, 1312, and 1313, can be used as the manipulator assemblies 1102. Manipulator arms 1310, 1311, 1312, 1313 eachinclude an instrument mount portion 1322 to which an instrument 1330 can be mounted, which is illustrated as being attached to manipulator arm 1310. While the manipulator system 1300 depicts four manipulator arms, various embodiments can include more or fewer manipulator arms.

[0172] Instrument mount portion 1322 can include a drive assembly 1323 and a cannula mount 1324, with a transmission mechanism 1334 of the instrument 1330 connecting with the drive assembly 1323, according to an embodiment. Cannula mount 1324 is configured to hold a cannula 1336 through which a shaft 1332 of instrument 1330 can extend to a surgery site during a surgical procedure. Drive assembly 1323 contains a variety of drive and other mechanisms that are controlled to respond to input commands at the operator input system 1106 and transmit forces to the transmission mechanism 1334 to actuate the instrument 1330. Although the embodiment of FIG. 13 shows an instrument 1330 attached to only manipulator arm 1310 for ease of viewing, an instrument can be attached to any and each of manipulator arms 1310, 1311, 1312, 1313.

[0173] FIG. 14 illustrates an example embodiment of a manipulator system 1400 that can be used as part of the manipulator system 1100. In FIG. 14, a portion of a manipulator arm 1440 of the manipulator system 1400 is shown with two instruments 1408, 1410 in an installed position. The schematic illustration of FIG. 14 depicts only two instruments for simplicity, but more than two instruments can be mounted in an installed position at the manipulator system 1400 as those having ordinary skill in the art are familiar. Each instrument 1408, 1410 includes a shaft 1420, 1430 having at a distal end a moveable end effector or an endoscope, camera, or other sensing device, and can or cannot include a wrist mechanism (not shown) to control the movement of the distal end.

[0174] In the embodiment of FIG. 14, the distal end portions of the instruments 1408, 1410 are received through a single port structure 1480 to be introduced into the patient. As shown, the port structure includes a cannula and an instrument entry guide inserted into the cannula. Individual instruments are inserted into the entry guide to reach a surgical site.

[0175] Transmission mechanisms 1485, 1490 are disposed at a proximal end portion of each shaft 1420, 1430 and connect through sterile adaptors 1450, 1460 with drive assemblies 1470, 1475, which contain a variety of internal mechanisms (not shown) that are controlled by a controller (e.g., at a control cart of a surgical system) to respond to input commands at a surgeon side console of a surgical system to transmit forces to the force transmission mechanisms 1485, 1490 to actuate instruments 1408, 1410.

[0176] The manipulator systems described herein are not limited to the embodiments of FIGS. 11, 12A-B, 13, and 14, and various other teleoperated, computer-assisted servomechanism configurations can be used with the embodiments described herein. The diameter or diameters of an instrument shaft and end effector are generally selected according to the size of the cannula with which the instrument will be used and depending on the surgical procedures being performed.

[0177] The visualization techniques described herein may be used for treatment confirmation and may further be extended to pre-operative treatment planning to treat stem cells, molecules, genetic material, organoids or other desired cells in the electrolytic electroporation ablated tissue prior to and during the period from ablation to regeneration.

[0178] Examples provided herein of both the design of visualization of systems and the clinical applications are not the limit of the uses of the combination of electroporation and electrolysis for endoluminal zones. Many configurations of ablation devices exist, as well as applications that would benefit from the use of the technology described herein.

[0179] It is to be appreciated that any one of the above embodiments or processes may be combined with one or more other embodiments and / or processes or be separated and / or performed amongst separate devices or device portions in accordance with the present systems, devices and methods.

[0180] Finally, the above discussion is intended to be merely illustrative of the present devices, apparatuses, systems, and methods and should not be construed as limiting the appended claims to any particular embodiment or group of embodiments. Thus, while the present disclosure has been described in particular detail with reference to exemplary embodiments, it should also be appreciated that numerous modifications and alternative embodiments may be practiced without departing from the broader and intended spirit and scope of the present disclosure as set forth in the claims that follow. Accordingly, the specification and drawings are to be regarded in an illustrative manner and are not intended to limit the scope of the appended claims.

Claims

CLAIMSWhat is claimed is:

1. A method comprising: treating tissue within a zone of a targeted region using ablation from an ablation device, the ablation comprising applying electroporation energy; imaging the zone to identify treated regions within the zone; and based on a location of the treated regions, performing additional ablation by the ablation device at selected additional regions within the zone.

2. The method of claim 1, further comprising delivering medication to the zone based on an appearance of the treated regions.

3. The method of claim 1, wherein the ablation comprises a combination of electroporation and electrolysis.

4. The method of claim 3, further comprising using white light endoscopy to image the zone, and wherein the treated regions have a different visual appearance than nontreated regions.

5. The method of claim 4, wherein the treated regions appear discolored.

6. The method of claim 4, further comprising: determining a degree of the ablation at the treated regions by image recognition or visual evaluation; and adjusting the additional ablation at the selected additional regions based on the degree of the ablation at the treated regions.

7. The method of claim 6, wherein said adjusting the additional ablation comprises controlling at least one of pulse duration, a current applied, a charge applied, a voltage applied, a number of pulses, or a combination thereof.

8. The method of claim 1, further comprising: prior to treating the tissue, marking at least one of a leading edge or a trailing edge of the zone using the ablation device to mark the tissue.

9. The method of claim 8, wherein said marking the zone comprises applying energy to the zone.

10. The method of claim 9, wherein said marking the zone comprises applying a combination of electroporation and electrolysis.

11. The method of claim 10, wherein said marking comprises applying a first amount of energy to the zone, and wherein said treating comprises applying a second amount of energy to the zone, wherein the first amount is less than the second amount.

12. The method of claim 1, further comprising tagging portions of images generated by said imaging to tag the selected additional regions.

13. The method of claim 12, further comprising: comparing said tagging with kinematic data from a robotic system used to perform the ablation; and generating position data for the selected additional regions based on said comparing, and wherein said performing additional ablation comprises using the position data to position the robotic system to treat the selected additional regions.

14. A method comprising: treating tissue within a zone of a target region using ablation including a combination of electroporation and electrolysis; imaging the zone; and identifying treated regions within the zone based on the imaging.

15. The method of claim 14, wherein said imaging uses white light endoscopy, narrow band imaging (NBI), fluorescence, chromoendoscopy, or a combination thereof.

16. The method of claim 15, wherein said identifying comprises determining whether the treated regions are different from at least one untreated region in appearance using image recognition, kinematic, shape sensing and / or visual evaluation.

17. The method of claim 16, further comprising determining a degree of ablation at the treated regions by image recognition or visual evaluation.

18. The method of claim 14, wherein treating the tissue is performed with an ablation device and prior to treating the tissue, marking at least one of a leading edge or a trailing edge of the zone using the ablation device to mark the tissue.

19. The method of claim 18, further comprising:comparing the leading edge, trailing edge, and / or overlapping edges with at least one of shape sensing data, kinematic data, or positional data; and positioning the ablation device between the leading and trailing edges based on the at least one of shape sensing data, kinematic data, or positional data to perform the ablation.

20. The method of claim 19, further comprising: marking the trailing edge; moving an imaging device to the trailing edge; identifying either a landmark or an electrolysis marker in the zone to identify the leading edge; moving the imaging device to a proximal portion of the treatment zone to measure a travel distance from the trailing edge to either the landmark or the electrolysis marker; moving the imaging device to the leading edge; pre-plotting a map including the zone; planning one or more treatment segments in the map based on a predetermined length in the zone, a treatment location, the travel distance or combinations thereof; and moving the ablation device to the one or more planned treatment segments.

21. The method of claim 20, wherein said pre-plotting a map comprises anatomical positioning.

22. The method of claim 20, further comprises dynamically adjusting one or more locations of the one or more treatment segments to update the planned one or more treatment segments.

23. A system comprising: an ablation device including a plurality of electrodes configured to contact tissue, the ablation device configured to perform ablation of the contacted tissue, the ablation comprising applying electroporation energy; an imaging device in proximity to the ablation device, configured to image a zone of a target region; and a controller coupled to the ablation device and the imaging device, the controller configured to: control the ablation device to mark tissue within the zone by controlling a charge applied to the plurality of electrodes; and control the imaging device to image the zone to visualize the marked regions.

24. The system of claim 23, wherein the controller is further configured to: based on a location of the marked regions determined based on imaging of the zone, control the ablation device to perform ablation at a region within the zone.

25. The system of claim 24, wherein the ablation comprises a combination of electroporation and electrolysis.

26. The system of claim 23, wherein controlling the ablation device to mark tissue comprises applying energy comprising a combination of electroporation and electrolysis.

27. The system of claim 26, wherein visualizing the marked regions comprises using white light endoscopy to image the zone, and wherein the marked regions have a different visual appearance than non-marked regions.

28. The system of claim 23, further comprising an elongate flexible device, wherein the plurality of electrodes comprise at least one electrode inserted through a working channel of the elongate flexible device.

29. The system of claim 23, further comprising: an elongate flexible device; and at least one expandable member at a distal portion of the elongate flexible device.

30. The system of claim 23, wherein the imaging device comprises an ultrasound imaging sensor and light source.

31. The system of claim 23, wherein the imaging device is configured to perform white light endoscopy, NBI, fluorescence, or a combination thereof.

32. The system of claim 23, further comprising an elongate flexible device including the imaging device, wherein the plurality of electrodes are distally attached to the elongate flexible device.

33. The system of claim 23, further comprising a processor, the processor configured to receive data from the imaging device, the processor configured to perform image recognition to identify the marked regions.

34. The system of claim 33, wherein the processor is further configured to determine a degree of ablation at treated regions based on the data from the imaging device, andwherein the controller is further configured to control charge, by selecting a duration, a voltage or range of voltages, a plurality of pulses, or combinations thereof, to be applied on the treated regions based on the degree of ablation.

35. The system of claim 34, further comprising a robotic system configured to robotically actuate the ablation device and the imaging device, wherein the processor is further configured to determine the region within the zone, and wherein the controller is configured to cause the robotic system to position the ablation device and the imaging device at the region within the zone.

36. The system of claim 35, wherein the controller is further configured to tag portions of one or more images generated by the imaging device to compare the tagged portions of the one or more images with at least one of shape sensing data, kinematic data, or positional data, and wherein the controller is configured to position the ablation device in proximity to the region within the zone based on the at least one of shape sensing data, kinematic data, or positional data.

37. The system of claim 24, further comprising a display configured to display one or more images generated by the imaging device, wherein the controller is further configured to allow a user visual evaluation to determine a degree of ablation at treated regions.

38. The system of claim 37, wherein the controller is further configured to allow a user to control at least one of a duration, a voltage or a number of pulses to be applied for performing additional ablation to the treated regions, or a position of the ablation device and the imaging device to be at the region within the zone based on the treated regions.

39. A non-transitory computer-readable storage media, the computer-readable storage media including instructions that when executed by a controller, cause the controller to: control an ablation device to treat tissue within a zone of a target region using ablation by controlling a charge applied to a plurality of electrodes of the ablation device, the ablation comprising applying electroporation energy; control an imaging device to image the zone to generate one or more images; andbased on a location of the treated regions determined based on the one or more images, control the ablation device to perform additional ablation at selected additional regions within the zone.

40. The non-transitory computer-readable storage media of claim 39, wherein the ablation comprises a combination of electroporation and electrolysis.

41. A method comprising: positioning an electrolytic device proximate a tissue region; and performing electrolysis to discolor the tissue region and provide a visual marker.

42. The method of claim 41, further comprising delivering energy for treatment based on a location of the visual marker.

43. The method of claim 41, wherein said performing electrolysis on the tissue comprises avoiding full ablation of the tissue region.

44. The method of claim 41, further comprising navigating a treatment device to a treatment location based in part on the visual marker.

45. The method of claim 44, further comprising performing electroporation using the electrolytic device positioned at the treatment location.

46. The method of claim 45, wherein a same electrode is used in said performing electrolysis and said performing electroporation.

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