# US 11,304,749 B2 · Systems, devices, and associated methods for neuromodulation with enhanced nerve targeting > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,304,749 B2 - Document ID: US11304749B2 - Status: Granted - Kind: B2 - Application number: 16/191,000 - Filed: 2018-11-14 - Published: 2019-05-23 - Granted: 2022-04-19 - Earliest claimed: 2017-11-17 - Assignees: Medtronic Ardian Luxembourg S.a.r.l. - Applicants: Medtronic Ardian Luxembourg S.a.r.l. - Inventors: Douglas A. Hettrick; Julie Trudel; Paul Coates; Robert J. Melder; Stefan S. Tunev; Martin Rothman; Sean Salmon - Web page: https://patentgrep.com/patent/US11304749B2 ## CPC - A61B 18/1492: {having a flexible, catheter-like structure, e.g. for heart ablation (A61B18/1477 takes precedence)} - A61B 5/0538: invasively, e.g. using a catheter - A61B 5/4836: {Diagnosis combined with treatment in closed-loop systems or methods (A61B5/0036 takes precedence)} - A61B 5/0035: {adapted for acquisition of images from more than one imaging mode, e.g. combining MRI and optical tomography} - A61B 5/0036: {including treatment, e.g., using an implantable medical device, ablating, ventilating} - A61B 5/0531: Measuring skin impedance - A61B 2018/00404: {Blood vessels other than those in or around the heart} - A61B 2018/00434: {Neural system} - A61B 2018/00577: {Ablation} - A61B 2018/00636: {Sensing and controlling the application of energy} - A61B 2018/00642: {with feedback, i.e. closed loop control} - A61B 2018/00648: {using more than one sensed parameter} - A61B 2018/00654: {with individual control of each of a plurality of energy emitting elements} - A61B 2018/00666: {using a threshold value} - A61B 2018/00702: {Power or energy} - A61B 2018/00755: {Resistance or impedance} - A61B 2018/00875: {Resistance or impedance} - A61B 2018/124: {switching the output to different electrodes, e.g. sequentially} - A61B 2018/1467: {using more than two electrodes on a single probe} - A61B 2018/165: {Multiple indifferent electrodes} - A61B 2018/167: {Passive electrodes capacitively coupled to the skin} - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) ## Abstract Systems and methods for neuromodulation therapy are disclosed herein. A method in accordance with embodiments of the present technology can include, for example, positioning a plurality of reference electrodes at the skin of a human patient and intravascularly positioning a plurality of ablation electrodes within a blood vessel lumen at a treatment site. The method can include obtaining impedance measurements between different combinations of the reference electrodes and the ablation electrodes and, based on the impedance measurements, identifying two or more electrode groups for treatment, where at least two of the electrode groups include a different one of the reference electrodes and a different one of the ablation electrodes. ## Claims ### Claim 1 A system, comprising: a neuromodulation catheter including: an elongated shaft having a distal portion configured to be intravascularly positioned at a target site within a blood vessel of a human patient, and a plurality of ablation electrodes spaced apart along the distal portion of the shaft, the plurality of ablation electrodes including a first ablation electrode and a second ablation electrode, wherein the ablation electrodes are configured to deliver neuromodulation energy to target nerves at or adjacent the target site; a plurality of reference electrodes configured to be positioned at the patient's skin, the reference electrodes including a first reference electrode and a second reference electrode; a controller configured to be communicatively coupled to the ablation electrodes and the references electrodes, wherein the controller is further configured to: obtain a first impedance measurement between the first ablation electrode and the first reference electrode, obtain a second impedance measurement between the first ablation electrode and the second reference electrode, obtain a third impedance measurement between the second ablation electrode and the first reference electrode, obtain a fourth impedance measurement between the second ablation electrode and the second reference electrode, compare the first impedance measurement, the second impedance measurement, the third impedance measurement, and the fourth impedance measurement to at least one reference impedance value, and based on comparison of the first impedance measurement, the second impedance measurement, the third impedance measurement, and the fourth impedance measurement to the at least one reference impedance value: (a) identify a first electrode group consisting of the first ablation electrode and one of the first reference electrode or the second reference electrode, and (b) identify a second electrode group consisting of the second ablation electrode and the other of the first reference electrode or the second reference electrode, wherein the first electrode group and the second electrode group are selected to achieve at least one of a desired direction or a desired three-dimensional shape of an electric field during subsequent energy delivery through at least one of the first electrode group or the second electrode group. ### Claim 2 (depends on 1) The system of claim 1 wherein the at least one reference impedance value comprises at least one of the first impedance measurement, the second impedance measurement, the third impedance measurement, or the fourth impedance measurement, and wherein the controller is configured to compare the first impedance measurement, the second impedance measurement, the third impedance measurement, and the fourth impedance measurement to the at least one reference impedance value by at least comparing at least one of the first, the second, the third, or the fourth impedance measurements to another of the first, the second, the third, and the fourth impedance measurements. ### Claim 3 (depends on 1) The system of claim 1 wherein the at least one reference impedance value comprises at least one of the first impedance measurement, the second impedance measurement, the third impedance measurement, or the fourth impedance measurement, and wherein the controller is configured to compare the first impedance measurement, the second impedance measurement, the third impedance measurement, and the fourth impedance measurement to the at least one reference impedance value by at least comparing each of the first, the second, the third, and the fourth impedance measurements to each of the other first, second, third, and fourth impedance measurements. ### Claim 4 (depends on 1) The system of claim 1 wherein the at least one reference impedance value comprises one or more stored impedance values, and wherein the controller is configured to compare the first impedance measurement, the second impedance measurement, the third impedance measurement, and the fourth impedance measurement to the at least one reference impedance value by at least comparing each of the first, the second, the third, and the fourth impedance measurements to the one or more stored impedance values. ### Claim 5 (depends on 1) The system of claim 1 wherein the controller is configured to generate an impedance map of the blood vessel at the target site based on the first, the second, the third, and the fourth impedance measurements. ### Claim 6 (depends on 1) The system of claim 1, further comprising an energy generator electrically coupled to the plurality of ablation electrodes, the plurality of reference electrodes, and the controller, and wherein, in response to the identification of the first electrode group and the second electrode group, the controller is configured to automatically cause the energy generator to: (a) deliver neuromodulation energy via a first electrical current through the first electrode group, and (b) deliver neuromodulation energy via a second electrical current through the second electrode group. ### Claim 7 (depends on 6) The system of claim 6 wherein the controller is an integral component of the energy generator and the controller and energy generator share a common housing. ### Claim 8 (depends on 1) The system of claim 1 wherein the controller is configured to indicate the first electrode group and the second electrode group to a user via a display. ### Claim 9 (depends on 1) The system of claim 1, further comprising an energy generator, wherein: the controller is configured to obtain the first, the second, the third, and the fourth impedance measurements while the ablation electrodes are delivering neuromodulation energy, and in response to the identification of the first electrode group and the second electrode group, the controller is configured to automatically cause the energy generator to— (a) stop delivering neuromodulation energy via a first electrical current through (i) the first electrode and (ii) one of the plurality of reference electrodes that is not in the first electrode group, and (b) start delivering neuromodulation energy via a second electrical current through the first electrode group. ### Claim 10 (depends on 1) The system of claim 1 wherein the distal portion of the shaft is configured to be positioned in at least one of a renal artery main vessel, a main bifurcation of the renal artery, or one or more renal branches distal of the main bifurcation of the renal artery. ### Claim 11 (depends on 1) The system of claim 1 wherein the distal portion of the shaft is configured to transform into a spiral shape such that, when the distal portion is placed in the spiral shape while positioned within the blood vessel, at least one of the ablation electrodes contacts an inner surface of a wall of the blood vessel. ### Claim 12 (depends on 1) The system of claim 1 wherein the number of reference electrodes is greater than the number of ablation electrodes. ### Claim 13 A method, comprising: positioning a plurality of reference electrodes at the skin of a human patient such that each of the reference electrodes is spaced apart from the other reference electrodes, wherein the reference electrodes include a first reference electrode and a second reference electrode; intravascularly positioning a neuromodulation assembly within a blood vessel of the patient at a treatment site, the neuromodulation assembly a first ablation electrode and a second ablation electrode spaced apart from the first ablation electrode; obtaining a first impedance measurement between the first ablation electrode and the first reference electrode; obtaining a second impedance measurement between the first ablation electrode and the second reference electrode; obtaining a third impedance measurement between the second ablation electrode and the first reference electrode; obtaining a fourth impedance measurement between the second ablation electrode and the second reference electrode; comparing the first impedance measurement, the second impedance measurement, the third impedance measurement, and the fourth impedance measurement to at least one reference impedance value; and based on the comparison of the first impedance measurement, the second impedance measurement, the third impedance measurement, and the fourth impedance measurement to the at least one reference impedance value: (a) identifying a first electrode group consisting of the first ablation electrode and one of the first reference electrode or the second reference electrode, and (b) identifying a second electrode group consisting of the second ablation electrode and the other of the first reference electrode or the second reference electrode, wherein the first electrode group and the second electrode group are selected to achieve at least one of a desired direction or a desired three-dimensional shape of an electric field during subsequent energy delivery through at least one of the first electrode group or the second electrode group. ### Claim 14 (depends on 13) The method of claim 13, further comprising: in response to identifying the first electrode group and the second electrode group, automatically delivering neuromodulation energy to the treatment site by delivering a first electrical current through the first electrode group and delivering a second electrical current through the second electrode group. ### Claim 15 (depends on 13) The method of claim 13 wherein positioning the plurality of reference electrodes includes positioning at least one of the plurality of reference electrodes at the patient's abdomen, at least one of the plurality of reference electrodes at the patient's torso, and at least one of the plurality of reference electrodes at one or both of the patient's legs. ### Claim 16 (depends on 13) The method of claim 13, wherein the at least one reference impedance value comprises at least one of the first impedance measurement, the second impedance measurement, the third impedance measurement, or the fourth impedance measurement, and wherein comparing the first impedance measurement, the second impedance measurement, the third impedance measurement, and the fourth impedance measurement to the at least one reference value comprises comparing at least one of the first, the second, the third, or the fourth impedance measurements to another of the first, the second, the third, and the fourth impedance measurements. ### Claim 17 (depends on 13) The method of claim 13, wherein the at least one reference impedance value comprises at least one of the first impedance measurement, the second impedance measurement, the third impedance measurement, or the fourth impedance measurement, and wherein comparing the first impedance measurement, the second impedance measurement, the third impedance measurement, and the fourth impedance measurement to the at least one reference value comprises comparing each of the first, the second, the third, and the fourth impedance measurements to each of the other first, second, third, and fourth impedance measurements. ### Claim 18 (depends on 13) The method of claim 13, wherein the at least one reference impedance value comprises one or more stored impedance values, and wherein comparing the first impedance measurement, the second impedance measurement, the third impedance measurement, and the fourth impedance measurement to the at least one reference value comprises further comprising comparing each of the first, the second, the third, and the fourth impedance measurements to the one or more stored impedance values. ### Claim 19 (depends on 13) The method of claim 13, further comprising generating an impedance map of the blood vessel at the target site based on the first, the second, the third, and the fourth impedance measurements. ### Claim 20 (depends on 13) The method of claim 13, further comprising indicating the first electrode group and the second electrode group to a user via a display. ### Claim 21 (depends on 13) The method of claim 13 wherein obtaining the first, the second, the third, and the fourth impedance measurements occur while the ablation electrodes are delivering neuromodulation energy. ### Claim 22 (depends on 13) The method of claim 13, further comprising: in response to the identification of the first electrode group and the second electrode group, automatically causing an energy generator to: (a) stop delivering neuromodulation energy via a first electrical current through (i) the first electrode and (ii) one of the plurality of reference electrodes that is not in the first electrode group, and (b) start delivering neuromodulation energy via a second electrical current through the first electrode group. ### Claim 23 (depends on 13) The method of claim 13 wherein intravascularly positioning the neuromodulation assembly includes positioning the neuromodulation assembly in at least one of a renal artery main vessel, a main bifurcation of the renal artery, or one or more renal branches distal of the main bifurcation of the renal artery.