Dervation therapy

Abstract

Example systems and techniques for denervation (e.g., renal denervation). In some examples, a processor determines one or more tissue characteristics of tissue proximate a target nerve and vessel. The processor may generate an estimated impact volume of denervation therapy delivered by a therapy delivery device disposed within the vessel based on the one or more tissue characteristics. The processor may generate a graphical user interface that includes a graphical representation of tissue near the target nerves and blood vessels and a graphical representation of the estimated impact volume.

Description

This application is a divisional application of the invention patent application entitled "Denervation Therapy", with an international application date of 2019-01-15, international application number PCT / US2019 / 013630, and application number 201980021865.7 entering the Chinese national phase.

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 62 / 621,351, filed on January 24, 2018, and entitled “Denervation Therapy.” Technical Field

[0002] In some examples, the present disclosure relates to systems and techniques for denervation therapy. Background Art

[0003] Overstimulation or overactivation of nerves may result in adverse effects in the organs or tissues served by the corresponding nerves. For example, in some patients, cardiac, circulatory, or renal disease may be associated with significant cardiorenal sympathetic hyperactivity. Stimulation of the renal sympathetic nerves can result in increased renin release, increased sodium (Na + ) reabsorption, or a decrease in renal blood flow. The kidneys may be directly damaged by nephrotoxicity due to the release of sympathetic neurotransmitters (such as norepinephrine) in the kidney in response to high renal nerve stimulation. In addition, increased renin release may ultimately increase systemic vasoconstriction, thereby aggravating hypertension. Such conditions can be alleviated by adjusting the activity of overactive nerves. Summary of the invention

[0004] The present disclosure describes devices, systems and techniques for determining one or more parameters of a denervation therapy, which may also be referred to as a neuromodulation therapy. Denervation therapy may include delivering electrical, chemical, optical or laser, microwave, radiation and / or thermal energy to a nerve so as to render the nerve inert, inactive, or otherwise completely or partially functionally impaired. The complete or partial functional impairment may be temporary or permanent. Systems and techniques according to the present disclosure may be used to estimate the volume of influence of a denervation stimulus delivered to a target nerve, and determine one or more parameters of a denervation therapy based on the volume of influence. In some examples, one or more parameters of a denervation therapy determined based on the estimated volume of influence may be used to automatically control a medical device to deliver denervation therapy to a patient. The volume of influence may be estimated based on a computer model generated based on a digital reconstruction of a region of the patient, the digital reconstruction indicating parameters such as tissue type and relative position. The volume of influence may be considered as a volume within a predetermined region of the patient, in which a denervation stimulus (also referred to herein as denervation stimulation) applied results in denervation, for example, by ablation or injury within the volume of influence. The volume of influence may indicate the effect of the denervation stimulation on the tissue. Thus, the activity of the nerves in the volume of influence may be reduced below a predetermined threshold, thereby causing the nerves in the volume of influence to exhibit reduced, substantially reduced, or substantially no activity. In some examples, denervation therapy may result in targeted nerve damage while avoiding damage to predetermined side effect areas, such as non-target non-neural tissue.

[0005] In some examples, the present disclosure describes example techniques that include: determining, by a processor, one or more tissue properties of tissue near a target nerve and a blood vessel; and determining, by the processor and based on the one or more tissue properties, an estimated volume of influence of a denervation therapy delivered by a therapy delivery device disposed within the blood vessel. The technique further includes generating, by the processor, a graphical user interface. The graphical user interface includes a graphical representation of the tissue near the target nerve and the blood vessel and a graphical representation of the estimated volume of influence.

[0006] In some examples, the present disclosure describes example techniques that include determining, by a processor, a computer model based on a digital reconstruction of a region of a patient, wherein the region includes target nerves and blood vessels. The computer model defines a spatial representation of one or more tissue properties in the region. The example techniques further include determining, by the processor and based on the computer model, an estimated volume of influence of a denervation therapy delivered by a therapy delivery device disposed within the blood vessel.

[0007] In some examples, the present disclosure describes an example system that includes a memory configured to store one or more tissue characteristics of tissue near a target nerve and blood vessel of a patient, and the example system also includes a processor coupled to the memory. The processor is configured to generate an estimated volume of influence of a denervation therapy delivered by a therapy delivery device disposed within a blood vessel based on the one or more tissue characteristics. The processor is further configured to generate a graphical user interface. The graphical user interface includes a graphical representation of tissue near the target nerve and blood vessel and a graphical representation of the estimated volume of influence.

[0008] In some examples, the present disclosure describes a non-transitory computer-readable medium that includes instructions that, when executed by at least one processor, cause the at least one processor to: determine one or more tissue properties of tissue near a target nerve and blood vessel of a patient, and based on the one or more tissue properties, determine an estimated volume of influence of a denervation therapy delivered by a therapy delivery device disposed within the blood vessel. The instructions further cause the at least one processor to generate a graphical user interface. The graphical user interface includes a graphical representation of the tissue near the target nerve and blood vessel and a graphical representation of the estimated volume of influence.

[0009] In some examples, the present disclosure describes an example system that includes: a device for determining one or more tissue properties of tissue near a target nerve and blood vessel of a patient; and a device for determining an estimated volume of influence of a denervation therapy delivered by a therapy delivery device disposed within the blood vessel based on the one or more tissue properties. The example system further includes a device for generating a graphical user interface. The graphical user interface includes a graphical representation of the tissue near the target nerve and blood vessel and a graphical representation of the estimated volume of influence.

[0010] In some examples, the present disclosure describes example techniques that include determining, by a processor, one or more tissue properties of tissue near a target nerve and a blood vessel of a patient. The example techniques include generating, by the processor and based on the one or more tissue properties, an estimated volume of influence of a denervation therapy delivered by a therapy delivery device disposed within a blood vessel. The example techniques include controlling, by the processor and based on the estimated volume of influence, a surgical device to move the therapy delivery device to a predetermined position within the blood vessel.

[0011] In some examples, the present disclosure describes an example system that includes a memory configured to store one or more tissue characteristics of tissue near a target nerve and a blood vessel of a patient, and the example system also includes a processor coupled to the memory. The processor is configured to determine one or more tissue characteristics of tissue near the target nerve and the blood vessel, and based on the one or more tissue characteristics, generate an estimated volume of influence of a denervation therapy delivered by a therapy delivery device disposed within the blood vessel. The processor is configured to control a surgical device based on the estimated volume of influence to move the therapy delivery device to a predetermined position within the blood vessel.

[0012] In some examples, the present disclosure describes an example system that includes: means for determining one or more tissue properties of tissue near a target nerve and a blood vessel of a patient; and means for generating an estimated volume of influence of a denervation therapy delivered by a therapy delivery device disposed within the blood vessel based on the one or more tissue properties. The example system includes means for controlling a movement device to move the therapy delivery device to a predetermined position within the blood vessel based on the estimated volume of influence.

[0013] Clause 1: A method comprising: determining, by a processor, one or more tissue properties of tissue proximate to a target nerve and blood vessel of a patient; generating, by the processor and based on the one or more tissue properties, an estimated volume of influence of a denervation therapy delivered by a therapy delivery device disposed within a blood vessel; and generating, by the processor, a graphical user interface comprising a graphical representation of the tissue proximate to the target nerve and blood vessel and a graphical representation of the estimated volume of influence

[0014] Clause 2: The method of clause 1, wherein the estimated volume of influence includes damage.

[0015] Clause 3: The method of clause 1 or 2, further comprising determining, by a processor and based on the estimated volume of influence, one or more treatment parameter values ​​for denervation treatment delivery.

[0016] Item 4: A method according to Item 3, wherein the estimated volume of influence of the denervation therapy includes a first estimated volume of influence of a first denervation therapy delivered by a therapy delivery device according to a first therapy procedure, the method further comprising: determining, by a processor, a second estimated volume of influence of a second denervation therapy delivered by the therapy delivery device according to a second therapy procedure, the second therapy procedure including at least one therapy parameter value different from the corresponding therapy parameter value of the first therapy procedure, wherein determining one or more therapy parameter values ​​for the denervation therapy delivery includes: selecting one of the first therapy procedure or the second therapy procedure based on the corresponding first estimated volume of influence and second estimated volume of influence.

[0017] Clause 5: A method according to clause 3, wherein the estimated volume of impact includes damage, and wherein determining one or more treatment parameter values ​​for denervation therapy delivery includes: selecting one or more treatment parameter values ​​that are determined to result in damage to the target nerve and avoid damage to a predetermined side effect area.

[0018] Clause 6: The method of clause 3, wherein the one or more treatment parameter values ​​include at least one of an electrical signal parameter, a thermal signal parameter, an ultrasound signal parameter, a microwave signal parameter, an optical signal parameter, or a chemical dose parameter.

[0019] Clause 7: The method of any of clauses 3 to 6, further comprising controlling, by the processor, the medical device to deliver denervation therapy to the target nerve according to the one or more therapy parameter values.

[0020] Clause 8: The method of any of clauses 1 to 7, further comprising generating, by the processor and based on the estimated volume of influence, an indexed position of a therapy delivery device within the patient.

[0021] Clause 9: The method of clause 8, wherein the index position is a position of a therapy delivery element of the therapy delivery device relative to the blood vessel.

[0022] Item 10: A method comprising: determining, by a processor, a computer model based on a digital reconstruction of a region of a patient, wherein the region includes target nerves and blood vessels, and wherein the computer model defines a spatial representation of one or more tissue properties in the region; and generating, by the processor and based on the computer model, an estimated volume of impact of a denervation therapy delivered by a therapy delivery device disposed within the blood vessel.

[0023] Clause 11: The method of clause 10, wherein the digital reconstruction is a three-dimensional (3D) digital reconstruction.

[0024] Clause 12: The method according to clause 10 or 11 further comprises: causing the computer model to obey the digital representation of a plurality of denervation stimuli by a processor, wherein each corresponding denervation stimulus of the plurality of denervation stimuli is delivered by a treatment delivery device at a corresponding predetermined orientation and at a corresponding predetermined position along a blood vessel; and after the computer model obeys each of the plurality of denervation stimuli, generating, by the processor, a corresponding response state of the computer model to the corresponding denervation stimulus.

[0025] Item 13: The method according to Item 12, wherein the area includes at least one non-target non-neural tissue, further comprising: selecting, by a processor, at least one denervation stimulus in response to determining that a corresponding response state associated with the selected at least one denervation stimulus indicates that the activity of the non-target non-neural tissue is greater than a threshold.

[0026] Clause 14: The method according to clause 12 further comprises: selecting, by a processor, at least one denervation stimulus in response to determining that a corresponding response state associated with at least one selected denervation stimulus indicates that the activity of a nerve is below a threshold; and determining, by the processor, a treatment program including the selected at least one denervation stimulus.

[0027] Clause 15: The method of clause 14, wherein the region includes at least one non-target non-neural tissue, and wherein the corresponding response state associated with the selected at least one denervation stimulus indicates that activity of the non-target non-neural tissue is greater than a threshold.

[0028] Clause 16: The method of any of clauses 13 to 15, further comprising controlling, by the processor, the medical device to deliver denervation stimulation to the region of the patient according to a treatment program.

[0029] Clause 17: The method of clause 16, wherein controlling the medical device comprises controlling the denervation stimulation generator based on a treatment program.

[0030] Clause 18: The method of any of clauses 10 to 17, wherein the one or more tissue properties include at least one of electrical impedance, thermal conductivity, acoustic impedance, optical transmittance, or chemical diffusivity.

[0031] Clause 19: The method of any one of clauses 10 to 18, wherein each of the plurality of denervation stimuli independently comprises at least one of radio frequency (RF) stimulation, thermal stimulation, cryostimulation, microwave stimulation, ultrasound stimulation, optical stimulation, or chemical stimulation.

[0032] Clause 20: The method of any of clauses 10 to 19, further comprising generating a digital reconstruction of the region of the patient based on a medical image of the region of the patient.

[0033] Clause 21: A method according to clause 20, wherein the medical image comprises at least one of a fluoroscopic image, a computer-assisted tomography (CAT) scan, a magnetic resonance imaging (MRI) image, a positron emission tomography (PET) scan, a tomographic image, an ultrasound image, or an optical image.

[0034] Clause 22: The method of any of clauses 10 to 21, wherein the computer model comprises a finite element model.

[0035] Clause 23: The method of any of clauses 10 to 22, wherein the at least one target nerve comprises a renal nerve and the blood vessel comprises a renal artery.

[0036] Item 24: A system comprising: a memory configured to store one or more tissue characteristics of tissue near target nerves and blood vessels of a patient; and a processor coupled to the memory, wherein the processor is configured to: generate an estimated volume of impact of a denervation therapy delivered by a therapy delivery device disposed within a blood vessel based on the one or more tissue characteristics; and generate a graphical user interface comprising a graphical representation of the tissue near the target nerves and blood vessels and a graphical representation of the estimated volume of impact.

[0037] Clause 25: The system of clause 24, wherein the estimated impact volume includes damage.

[0038] Clause 26: The system of clause 24 or 25, wherein the processor is configured to determine one or more treatment parameter values ​​for denervation therapy delivery based on the estimated volume of influence.

[0039] Clause 27: A system according to clause 26, wherein the estimated volume of influence of the denervation therapy includes a first estimated volume of influence of a first denervation therapy delivered by the therapy delivery device according to a first therapy procedure, and the processor is further configured to: determine a second estimated volume of influence of a second denervation therapy delivered by the therapy delivery device according to a second therapy procedure, the second therapy procedure including at least one therapy parameter value different from the corresponding therapy parameter value of the first therapy procedure, wherein the processor is configured to: determine one or more therapy parameter values ​​for denervation therapy delivery by selecting one of the first therapy procedure or the second therapy procedure based on the corresponding first estimated volume of influence and second estimated volume of influence.

[0040] Clause 28: A system according to clause 26 or 27, wherein the estimated impact volume includes damage and wherein the processor is configured to: determine one or more treatment parameter values ​​for denervation therapy delivery by selecting one or more treatment parameter values ​​that are determined to result in damage to the target nerve and avoid damage to a predetermined side effect area.

[0041] Clause 29: A system according to any of clauses 26 to 28, wherein the one or more treatment parameter values ​​include at least one of an electrical signal parameter, a thermal signal parameter, an ultrasound signal parameter, a microwave signal parameter, an optical signal parameter, or a chemical dosage parameter.

[0042] Clause 30: The system of any of clauses 26 to 29, wherein the processor is further configured to control the medical device to deliver denervation therapy to the target nerve according to the one or more therapy parameter values.

[0043] Clause 31: The system of any of clauses 24 to 30, wherein the processor is further configured to generate an indexed position of a therapy delivery device within the patient based on the estimated volume of influence.

[0044] Clause 32: The system of clause 31, wherein the index position is a position of a therapy delivery element of the therapy delivery device relative to the blood vessel.

[0045] Clause 33: The system of clause 26, further comprising a therapy generator configured to generate the denervation stimulation based on one or more therapy parameter values.

[0046] Clause 34: The system of clause 33, further comprising a therapy delivery device configured to be coupled to the therapy generator, wherein the therapy generator is configured to deliver the denervation therapy to the patient via the therapy delivery device.

[0047] Clause 35: A system according to any of clauses 24 to 34, wherein at least one treatment delivery device comprises at least one of an electrode, a radio frequency (RF) probe, a thermal probe, a cryoprobe, a microwave probe, an ultrasound probe, a light source, or a chemical injector.

[0048] Clause 36: The system of any of clauses 24 to 35, further comprising an imaging system configured to image target nerves and blood vessels.

[0049] Item 37: A system according to item 36, wherein the imaging system includes at least one of a fluoroscopic examination system, a computer-assisted tomography (CAT) scanning system, a magnetic resonance imaging (MRI) system, a positron emission tomography (PET) scanning system, an electrical impedance tomography (EIT) system, an ultrasound system, or an optical imaging system.

[0050] Clause 38: The system of any of clauses 24 to 37, wherein the target nerve comprises a renal nerve, and wherein the blood vessel comprises a renal artery.

[0051] Item 39: A non-transitory computer-readable medium comprising instructions that, when executed, cause at least one processor to: determine one or more tissue characteristics of tissue near target nerves and blood vessels of a patient; generate an estimated volume of impact of a denervation therapy delivered by a therapy delivery device disposed within the blood vessel based on the one or more tissue characteristics; and generate a graphical user interface comprising a graphical representation of the tissue near the target nerves and blood vessels and a graphical representation of the estimated volume of impact.

[0052] Clause 40: The non-transitory computer readable medium of clause 39, wherein the estimated volume of influence includes damage.

[0053] Clause 41: The non-transitory computer readable medium of clause 39 or 40, further comprising instructions that, when executed, cause at least one processor to determine one or more treatment parameter values ​​for denervation treatment delivery based on the estimated volume of influence.

[0054] Item 42: A non-transitory computer-readable medium according to Item 41, wherein the estimated volume of influence of the denervation therapy includes a first estimated volume of influence of a first denervation therapy delivered by a therapy delivery device according to a first therapy procedure, and wherein the non-transitory computer-readable medium further includes instructions that, when executed, cause at least one processor to: determine a second estimated volume of influence of a second denervation therapy delivered by the therapy delivery device according to a second therapy procedure, the second therapy procedure including at least one therapy parameter value that is different from the corresponding therapy parameter value of the first therapy procedure, wherein the instructions cause the processor to: determine one or more therapy parameter values ​​for denervation therapy delivery by selecting one of the first therapy procedure or the second therapy procedure based on the corresponding first estimated volume of influence and the second estimated volume of influence.

[0055] Clause 43: Non-transitory computer-readable medium according to clause 41 or 42, wherein the estimated impact volume includes damage, and wherein the instructions cause at least one processor to: determine one or more treatment parameter values ​​for denervation therapy delivery by at least selecting one or more treatment parameter values ​​that are determined to result in damage to the target nerve and avoid damage to a predetermined side effect area.

[0056] Clause 44: A non-transitory computer readable medium according to any of clauses 41 to 43, wherein the one or more treatment parameter values ​​include at least one of an electrical signal parameter, a thermal signal parameter, an ultrasound signal parameter, a microwave signal parameter, an optical signal parameter, or a chemical dosage parameter.

[0057] Clause 45: The non-transitory computer readable medium of any of clauses 41 to 44, further comprising instructions that, when executed, cause at least one processor to control a medical device to deliver denervation therapy to a target nerve according to one or more therapy parameter values.

[0058] Clause 46: The non-transitory computer readable medium of any of clauses 39 to 45, further comprising instructions that, when executed, cause at least one processor to generate an indexed position of a therapy delivery device within the patient based on the estimated volume of influence.

[0059] Clause 47: The non-transitory computer readable medium of clause 46, wherein the index location is a location of a therapy delivery element of the therapy delivery device relative to the blood vessel.

[0060] Clause 48: The non-transitory computer readable medium of any of clauses 39 to 47, wherein the target nerve comprises a renal nerve, and wherein the blood vessel comprises a renal artery.

[0061] Item 49: A system comprising: a device for determining one or more tissue characteristics of tissue near target nerves and blood vessels of a patient; a device for generating an estimated volume of impact of a denervation therapy delivered by a therapy delivery device disposed within a blood vessel based on the one or more tissue characteristics; and a device for generating a graphical user interface comprising a graphical representation of the tissue near the target nerves and blood vessels and a graphical representation of the estimated volume of impact.

[0062] Clause 50: The system of clause 49, further comprising means for determining one or more treatment parameter values ​​for denervation therapy delivery based on the estimated volume of influence.

[0063] Clause 51: A system according to clause 50, wherein the estimated volume of impact includes damage, and wherein the means for determining one or more tissue characteristics includes means for selecting one or more treatment parameter values ​​determined to result in damage to the target nerve and avoid damage to a predetermined side effect area.

[0064] Clause 52: The system of clause 50, wherein the estimated volume of influence includes lesions, and wherein the means for determining one or more tissue characteristics comprises means for selecting one or more treatment parameter values ​​determined to avoid lesions of a predetermined side effect region.

[0065] Clause 53: The system of any of clauses 50 to 52, wherein the target nerve comprises a renal nerve, and wherein the blood vessel comprises a renal artery.

[0066] Clause 54: The system of any of clauses 50 to 53, further comprising means for generating a denervation therapy for the patient based on the one or more therapy parameter values.

[0067] Item 55: A method comprising: determining, by a processor, one or more tissue characteristics of tissue near a target nerve and blood vessel of a patient; generating, by the processor and based on the one or more tissue characteristics, an estimated volume of impact of a denervation therapy delivered by a therapy delivery device disposed within the blood vessel; and controlling, by the processor and based on the estimated volume of impact, a surgical device to move the therapy delivery device to a predetermined position within the blood vessel.

[0068] Clause 56: The method of clause 55, further comprising determining, by the processor and based on the estimated volume of influence, one or more treatment parameter values ​​for denervation treatment delivery.

[0069] Clause 57: The method of clause 56, wherein the estimated volume of impact includes damage, and wherein determining one or more treatment parameter values ​​for denervation therapy delivery comprises selecting one or more treatment parameter values ​​that are determined to result in damage to the target nerve and avoid damage to a predetermined side effect area.

[0070] Clause 58: The method of clause 56, wherein the estimated volume of influence includes lesions, and wherein determining one or more treatment parameter values ​​for denervation therapy delivery comprises selecting one or more treatment parameter values ​​determined to avoid lesions of a predetermined side effect region.

[0071] Clause 59: The method of any of clauses 56 to 58, further comprising causing, by the processor, the therapy delivery device to deliver denervation therapy to the patient based on the one or more therapy parameter values.

[0072] Item 60: A system comprising: a memory configured to store one or more tissue characteristics of tissue near a target nerve and blood vessel of a patient; and a processor coupled to the memory, wherein the processor is configured to: determine one or more tissue characteristics of tissue near the target nerve and blood vessel; generate an estimated impact volume of a denervation therapy delivered by a therapy delivery device disposed within the blood vessel based on the one or more tissue characteristics; and control a surgical device to move the therapy delivery device to a predetermined position within the blood vessel based on the estimated impact volume.

[0073] Clause 61: The system of clause 60, wherein the processor is further configured to determine one or more treatment parameter values ​​for denervation therapy delivery based on the estimated volume of influence.

[0074] Clause 62: A system according to clause 61, wherein the estimated impact volume includes damage, and wherein the processor is configured to: determine one or more treatment parameter values ​​for denervation therapy delivery by selecting one or more treatment parameter values ​​that are determined to result in damage to the target nerve and avoid damage to a predetermined side effect area.

[0075] Clause 63: A system according to clause 61, wherein the estimated impact volume includes damage, and wherein the processor is configured to: determine one or more treatment parameter values ​​for denervation therapy delivery by selecting one or more treatment parameter values ​​determined to avoid damage to a predetermined side effect area.

[0076] Clause 64: The system of any of clauses 61 to 63, wherein the processor is further configured to control the medical device to deliver denervation therapy to the patient based on the one or more therapy parameter values.

[0077] Clause 65: The system of any of clauses 60 to 64, further comprising a drive unit coupled to the processor and the therapy delivery device.

[0078] Item 66: A system comprising: a device for determining one or more tissue characteristics of tissue near a target nerve and blood vessel of a patient; a device for generating an estimated impact volume of a denervation therapy delivered by a therapy delivery device disposed within the blood vessel based on the one or more tissue characteristics; and a device for controlling a moving device to move the therapy delivery device to a predetermined position within the blood vessel based on the estimated impact volume.

[0079] Clause 67: The system of clause 66, further comprising means for determining one or more treatment parameter values ​​for denervation therapy delivery based on the estimated volume of influence.

[0080] Clause 68: A system according to clause 66, wherein the estimated volume of impact includes damage, and wherein the means for determining one or more tissue characteristics includes means for selecting one or more treatment parameter values ​​determined to result in damage to the target nerve and avoid damage to a predetermined side effect area.

[0081] Clause 69: The system of clause 66, wherein the estimated volume of influence includes lesions, and wherein the means for determining one or more tissue characteristics comprises means for selecting one or more treatment parameter values ​​determined to avoid lesions in a predetermined side effect region.

[0082] Clause 70: The system of any of clauses 67 to 69, further comprising means for generating a denervation therapy for the patient based on the one or more therapy parameter values.

[0083] Clause 71: The system of any of clauses 66 to 70, further comprising means for moving the therapy delivery device along the blood vessel.

[0084] The details of one or more aspects of the disclosure are set forth in the accompanying drawings and description below. Other features, objects, and advantages of the techniques described in this disclosure will be apparent from the description, drawings, and claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0085] Reference is now made to the accompanying drawings, wherein elements with like reference numerals refer to similar elements throughout, and wherein:

[0086] Figure 1A is a schematic and conceptual illustration of an example system including a denervation therapy delivery device and a therapy generator.

[0087] Figure 1B is a schematic and conceptual illustration of an example denervation therapy delivery device including at least one electrode.

[0088] Figure 2 yes Figure 1A Schematic and conceptual illustration of deployment of an example system for delivering denervation therapy.

[0089] Figure 3 is a schematic and conceptual illustration of an example programmer coupled to an imaging system and an example therapy delivery device.

[0090] Figure 4 is a flow chart illustrating an example technique for delivering denervation therapy.

[0091] Figure 5 is a flow chart illustrating an example technique for generating a computer model of a region of a patient.

[0092] Figure 6 is a flow chart illustrating an example technique for delivering denervation therapy.

[0093] Figure 7 is a flow chart illustrating an example technique for delivering denervation therapy.

[0094] Figure 8 It shows that Figure 3 Schematic representation of an example graphical user interface (GUI) presented on a display of a programmer's user interface.

[0095] Fig. 9 is available in Figure 3 A schematic illustration of another example of a GUI presented on a display of a programmer.

[0096] Fig.10 is a conceptual and schematic illustration of the sympathetic nervous system (SNS) and the brain's communication with the body via the SNS.

[0097] Fig.11 is a conceptual anatomical view of the nerves that innervate the left kidney to form the renal plexus surrounding the left renal artery.

[0098] Fig. 12A and Fig. 12B Conceptual anatomical views of the human body depicting efferent and afferent neural communications between the brain and kidneys, respectively.

[0099] Fig.13A and Fig. 13B Conceptual anatomical views of the human arterial and venous vasculature, respectively. DETAILED DESCRIPTION

[0100] Denervation therapy can be used to render the target nerve inert, inactive, or otherwise completely or partially functionally impaired, such as by ablation or injury of the target nerve. In some examples, the target nerve can be a member of a nerve bundle, and denervation therapy can be used to ablate or damage the nerve bundle. After denervation, the transmission of nerve signals along the target nerve may be reduced, or even prevented from being transmitted along the target nerve. Denervation of overactive nerves may provide therapeutic benefits to patients. For example, renal denervation can alleviate symptoms associated with overstimulation of the renal sympathetic nerves. Denervation therapy may include delivering electrical and / or thermal energy to the target nerve, and / or by delivering a chemical agent to the target nerve. In the case of renal denervation therapy, denervation energy or a chemical agent may be delivered, for example, via a treatment delivery device (e.g., a catheter) disposed in a blood vessel (e.g., a renal artery) near the renal nerve. It may be desirable to select one or more parameters of the denervation treatment to achieve delivery of sufficient energy or chemical agent to denervate the target nerve while minimizing or avoiding undue effects of the denervation energy or chemical agent on non-target non-neural tissue, non-target nerves, or one or more side effect areas. In other cases, it may be desirable to select one or more parameters of the denervation treatment to minimize or avoid effects of the denervation energy or chemical agent on non-target non-neural tissue, non-target nerves, or one or more side effect areas.

[0101] The present disclosure describes devices, systems, and techniques for determining one or more parameters of a denervation therapy using a computer model that takes into account patient-specific tissue properties and anatomical structures. The one or more parameters of the denervation therapy may include, for example, electrical signal parameters, thermal signal parameters, ultrasound signal parameters, microwave signal parameters, optical signal parameters, or chemical dosage parameters, and may vary depending on the type of therapy delivered by the medical device for providing the denervation therapy. The one or more determined parameters of the denervation therapy may be stored by a device (such as a medical device programmer or a medical device) as a treatment program that can be used by the medical device to generate and deliver the denervation therapy to the patient.

[0102] In some examples, the example system includes a memory configured to store one or more tissue characteristics of tissue near the target nerve and blood vessel of the patient, and the example system also includes a processor coupled to the memory. The processor can be configured to determine one or more characteristics (also referred to herein as "tissue parameters") of tissue near the target nerve and the corresponding blood vessel (e.g., a blood vessel near the target nerve, through which the target nerve can be accessed). The processor can be configured to generate an estimated volume of influence of denervation therapy delivered by a treatment delivery device disposed in the blood vessel based on one or more tissue characteristics and characteristics of the treatment delivery device (e.g., the number, size and position of electrodes, the position of the opening for delivering chemical agents, etc.). The estimated volume of influence may extend beyond the area or volume of tissue in which the stimulation is delivered. In some examples, the electric field or another denervation stimulus may extend within or through the volume of the first tissue in a first tissue volume, but the volume of influence may extend beyond the first tissue volume. For example, the temperature of tissue outside the first volume may rise above the denervation temperature or another denervation parameter threshold. In some examples, the processor may generate an estimated volume of influence using a computer model of a spatial representation of tissue in a defined area, the computer model including corresponding tissue characteristics (e.g., thermal conductivity, electrical conductivity, density, etc.). The processor may be configured to generate a graphical user interface (GUI) including a graphical representation of tissue proximate to the target nerve and corresponding blood vessel and a graphical representation of the estimated volume of influence.

[0103] In some examples, based on the estimated volume of influence, the processor may determine a treatment program that defines one or more treatment delivery parameters for generating an effective denervation treatment (e.g., denervation stimulation). The denervation stimulation may be configured to cause the target nerve to exhibit activity below a threshold while causing the activity of non-target tissue to be above the threshold. The denervation stimulation may be electrical, thermal, chemical, optical, microwave, radiation, or any suitable type of stimulation that may affect the properties of the tissue subjected to the delivered stimulation.

[0104] In some examples, the processor may determine the effect of different treatment parameter values ​​(a set of treatment parameter values ​​that define the denervation stimulation delivered during a treatment session may be referred to as a treatment program or a set of treatment parameter values) on the impact volume, and select a treatment program from different treatment programs based on the corresponding impact volume. For example, the processor may define a first estimated impact volume of a first denervation treatment delivered by a treatment delivery device according to a first treatment program. The processor may also determine a second estimated impact volume of a second denervation treatment delivered by a treatment delivery device according to a second treatment program, wherein the second treatment program includes at least one treatment parameter value that is different from the corresponding treatment parameter value of the first treatment program. The processor may determine one or more treatment parameter values ​​for the denervation treatment by selecting one of the first treatment program or the second treatment program based on the corresponding first estimated impact volume and the second estimated impact volume. In other examples, the processor may select from any suitable number of treatment programs based on the corresponding impact volume.

[0105] In some examples, multiple treatment programs can provide effective results for specific patients, for example, due to similar targeting of renal nerves or other nerves or target tissue sites of interest by denervation stimulation. However, the results of denervation therapy delivered according to different treatment programs may differ from each other in one or more ways. For example, some treatment programs may define denervation stimulation that requires more power to generate compared to one or more other treatment programs, thereby making some treatment programs more efficient (for example, in terms of power usage) than other treatment programs. As another example, some treatment programs may cause more non-target tissue damage compared to one or more other treatment programs. Therefore, the treatment program selected by the processor of the device (for example, a medical device programmer) or by a clinician is not only based on the estimated damage of the target tissue site, but also based on one or more other factors, such as the power consumed during the treatment session, the impact on non-target tissue sites, etc. In some examples, the processor of the device can sort the list of treatment programs based on one or more of these other factors (for example, in ascending or descending order based on power consumption, non-target tissue sites affected by treatment, etc.), and present the sorted list of treatment programs to the user via the display of the device. The processor may then select one or more therapy programs for controlling delivery of therapy to the patient in response to patient input, or automatically based on a first one or more predetermined numbers of therapy programs in the ranked list.

[0106] In some examples, a processor may generate a plurality of treatment programs (which may differ from each other in at least one treatment parameter value for a given treatment parameter) and determine a plurality of volumes of influence, each of which is associated with a corresponding treatment program in the plurality of treatment programs. The processor may select a volume of influence from the plurality of volumes of influence, for example, at least one volume of influence that extends to the tissue of interest while avoiding non-target sites (e.g., predetermined side effect sites). Based on at least one selected volume of influence, the processor may select a treatment program from the plurality of treatment programs. The selected treatment program may generate at least one selected volume of influence at the target tissue site, such that the at least one volume of influence does not affect or extend into the non-target tissue site.

[0107] In some examples, the processor may determine the computer model based on a digital reconstruction of a region of the patient, wherein the region includes a target nerve and a corresponding blood vessel. The processor may generate the digital reconstruction, for example, using a patient-specific image of the region generated using any suitable imaging modality.

[0108] Due to variations in the volume of influence for a given set of treatment delivery parameter values, denervation of a target nerve may not be fully predictable. Variations in the volume of influence may be due to, for example, variations in tissue properties of tissue adjacent to the target nerve or blood vessel. For example, other nerves, bones, tendons, muscles, fat, lymph nodes, blood vessels, calcium deposits, and / or organs may be located in the same adjacent area as the target nerve, and the tissue properties of that tissue may affect the way in which denervation therapy affects that tissue. Example tissue properties include electrical impedance or conductivity (e.g., isotropic or anisotropic conductivity), thermal conductivity, acoustic impedance, chemical diffusivity, or optical transmittance.

[0109] During the delivery of renal denervation therapy, an indication of the actual nerve location or a technique for verifying the actual nerve denervation may not be readily available. Although the clinician may obtain some feedback, for example, by sensing one or more patient parameters (e.g., temperature and / or impedance, vasoconstriction, heart rate, blood flow, and / or patient movement in the vicinity of the treatment delivery device), such feedback may not be efficient or effective in directing the denervation therapy toward the target nerve and / or avoiding damage to the predetermined side effect area. The predetermined side effect area may include non-target tissue, for example, non-neural tissue, or tissue that is otherwise not expected to receive treatment but may be susceptible to damage from denervation stimulation. In some examples, the side effect area may include fat, muscle, bone, or other tissue or organ, or nerves that are not expected to receive denervation. The clinician may provide feedback indicating the predetermined side effect area to the medical device programmer, or the predetermined side effect area may be pre-stored by the medical device programmer and programming is not required for the clinician's input. The computer models described herein can be used to better estimate and visualize the effects of denervation therapy on target nerves and / or tissues near the target nerves, and thereby generate treatment procedures that better target the target nerves and / or better avoid adverse effects on non-target tissues.

[0110] For example, a computing device may use a computer model to evaluate multiple denervation locations, and for each location, the computing device may determine a denervation treatment parameter value (e.g., a value for delivering electrical, thermal, chemical, microwave, radiation, or optical stimulation, and in the case of electrical or thermal stimulation, an electrode for delivering the stimulation) for achieving effective damage at the location. The computing device may then evaluate the entire data set, including the treatment parameter values ​​associated with the different locations, to determine a subset of locations (selected from the multiple denervation locations) at which treatment may be delivered to achieve the overall denervation goal for the patient's region. The treatment parameter values ​​and corresponding locations may then be used to program a medical device that is configured to deliver denervation treatment to the patient and / or may be presented to a clinician via a user interface of the computing device as a recommended treatment plan.

[0111] In some examples, treatment parameter values ​​determined using patient-specific tissue properties and anatomical structures can be used to perform guided denervation of a target nerve. For example, a denervation treatment delivery device (e.g., a catheter) can be navigated through a blood vessel and positioned, oriented, and deployed manually by a clinician with the assistance of a graphical user interface or automatically by a device (such as a computer-controlled robotic surgical device). The graphical user interface may include a graphical representation of tissue near the target nerve and blood vessel, as well as a graphical representation of an estimated volume of impact of the treatment delivered by the treatment delivery device and according to a specific treatment procedure.

[0112] The anatomical structure surrounding the renal artery of a human subject is relatively complex and includes several different types of tissues with different thermal and / or electrical properties. Further, the position of the renal nerves relative to the renal artery may vary along the length of the renal artery. For example, the nerve bundles of the renal nerves may be further away from the renal artery at a relatively more proximal position relative to the aorta. The closer to the kidney, the closer the nerve bundles of the renal nerves may be to the renal artery. In addition, certain types of tissue, such as arteries and veins, may act as electrical or thermal conductors, which may also affect the energy required to ablate the renal nerves.

[0113] Due to different tissue properties and different positions of the renal nerves relative to the renal artery, the treatment delivery parameters for effective renal denervation therapy may be different depending on the location along the renal artery where the renal denervation therapy is delivered. For example, due to the change in the distance between the renal nerves and the renal artery, more energy may need to be applied to ablate or damage the renal nerves when the denervation therapy is delivered farther from the kidney. However, it is desirable not to set the energy too high so as to adversely affect other areas of the tissue (e.g., side effect areas). Using the computer modeling techniques described herein and the estimated impact volume of renal denervation, the processor of the medical device programmer can determine, based on tissue characteristics, certain areas of the tissue (referred to herein as side effect areas or non-target areas) that can be avoided and / or the energy level at which denervation of the renal nerves is achieved.

[0114] Several factors that increase the complexity of selecting effective treatment parameter values ​​for denervation therapy may be at least partially attributed to the patient's anatomical structure. For example, different patients may have different tissue types closer to the renal artery, and some patients' renal nerves may be closer to the renal artery than other patients. In some examples, the blood flow rate in a blood vessel (e.g., a renal artery) may have an impact on the volume of influence. For example, a higher blood flow rate may result in relatively faster heat dissipation, thereby resulting in a smaller volume of influence for a given denervation stimulus compared to the volume of influence associated with a lower blood flow rate. Compared to denervation therapy delivered in a temporary manner without the assistance of computer modeling described herein, the devices, systems, and techniques described herein that take into account patient-specific anatomical structures and tissue properties (including blood flow rates at or near target tissue sites) can help increase the efficacy and efficiency of denervation therapy delivered by a medical device or both. Patient-specific anatomical structures may include, for example: the position and relative arrangement of different anatomical structures (e.g., organs, blood vessels, target tissue sites, etc.) of the patient, and the size of one or more blood vessels, which may correspond to the blood flow rate through the blood vessels, and therefore to the thermal conductivity and / or electrical conductivity of the blood vessels.

[0115] In some examples, example techniques may include pre-denervation imaging, digital reconstruction, and computer modeling of a patient region. A processor of a device (e.g., a medical device programmer) may generate a computer model based on the reconstruction of the patient region. The processor may determine denervation therapy parameter values ​​based on an estimated volume of influence determined using the computer model, and determine a denervation therapy procedure based on the denervation therapy parameters. For example, the processor may use images generated by preoperative visualization to digitally reconstruct (e.g., three-dimensional (3D)) anatomical structures around the renal artery. In some examples, the image may include a resolution sufficient to determine a single nerve bundle. In other examples, the resolution may be sufficient to determine relatively large structures (e.g., muscle, fat, lymph nodes, blood vessels, or the gastrointestinal tract), and sufficient to measure the size and location of different tissue sites to allow reconstruction of a relatively accurate 3D model of the patient's region.

[0116] The processor may use digital reconstruction to prepare a model, such as a computer model or a bench model. The bench model may include a physical model of the area of ​​the patient to be denervated, such as a modeled or sculpted model, a model generated using rapid prototyping, or an additively manufactured model. In some examples, the bench model may include different materials with different properties, representing different types of tissue or anatomical features in the area of ​​the patient. The bench model may include sensors at different locations for sensing stimulation received from a denervation stimulation source at corresponding locations in the bench model. Based on the stimulation sensed at different locations in the bench model (the development of damage at the corresponding locations can be estimated), the clinician can determine parameters for denervation treatment, including the location and amplitude of the denervation stimulation to be delivered at different locations.

[0117] In lieu of, or in addition to, a gantry model, a clinician or computing device may use a computer model of the patient region to determine the effects of different denervation stimulations and denervation locations. For example, the computer model may take into account differences and heterogeneity in tissue properties of different tissue types by incorporating electrical, thermal, and other appropriate properties associated with each tissue type. The processor may use the computer model to perform simulations of different treatment delivery procedures. For example, the processor may apply simulated denervation stimulations with various denervation amplitude amounts at various locations along a blood vessel in the computer model. The processor may monitor the effects of the denervation stimulation on the denervated target nerves and other non-target tissues adjacent to the nerves in the model based on the estimated volume of influence of the denervation stimulation. The processor may therefore use the computer model to generate a treatment plan, including a set of target denervation stimulation delivery locations, orientations, and amplitudes to be delivered at the site, to achieve a target level of denervation.

[0118] The processor of the medical device can use a treatment plan (also referred to herein as a treatment program) to control the denervation treatment provided to the patient. For example, a programmer can send a treatment program to a medical device including a treatment generator, wherein the treatment program can indicate the amount of energy to be delivered at one or more treatment locations along a blood vessel. For example, a treatment delivery device may include a radio frequency (RF) electrode on a catheter that is introduced and advanced along a patient's blood vessel. The position of the catheter can be provided to the treatment generator via direct interaction with a physician input or by receiving feedback from an imaging system (e.g., a fluoroscopic examination system, or some other tool for measuring the position or orientation of the catheter / electrode).

[0119] Even if the imaging resolution is insufficient to find or identify a specific nerve (e.g., a renal nerve), example systems and techniques according to the present disclosure can be used to determine the maximum denervation stimulus that can be delivered at a location to create the maximum possible damage without damaging non-target tissue. If the imaging resolution allows the nerve to be identified, example systems and techniques according to the present disclosure can be used to determine the appropriate location and treatment parameters for increasing nerve denervation above a target threshold while maintaining non-target tissue damage below the threshold.

[0120] In contrast to some proposed renal denervation techniques, in which clinicians control the delivery of RF energy via a treatment delivery device (e.g., using monopolar or multipolar electrodes on a balloon, basket, or spiral) according to an empirical procedure, the devices, systems, and techniques described herein can be used to determine treatment parameter values / settings for effective denervation therapy based on the patient's specific anatomy. Parameters may include, for example, one or more orientations and / or positions of the treatment delivery device in the patient's body (e.g., anterior, posterior, or inferior superior), energy delivery parameters (e.g., frequency, duty cycle, and / or amplitude of the RF signal), and any other suitable parameters. For example, as described in further detail below, a processor of a medical device programmer, alone or with the assistance of a clinician, can determine an orientation and / or position of a treatment delivery device in the patient's body or one or more energy delivery parameters that are expected to achieve effective denervation of target nerves and substantially avoid adversely affecting other non-target tissues of the patient. Rather than introducing a catheter into a patient's renal artery and delivering RF energy according to a general set of rules that apply to a wide range of anatomical variations, the present invention relates to a method of delivering RF energy to the patient's renal artery in accordance with a general set of rules that apply to a wide range of anatomical variations. Figures 1A to 13B The described example devices, systems, and techniques can provide renal denervation therapy that is generated based on a patient's specific anatomy. Such therapy may be more effective because it can better deliver denervation stimulation to the target nerve and / or avoid adversely affecting non-target tissue. In addition, in some cases, renal denervation stimulation generated based on a patient's specific anatomy may result in a more efficient medical procedure because it can better distribute the denervation stimulation to denervate the target nerve during the first passage through the blood vessel using the treatment delivery device. As discussed below, it is desirable to reduce the amount of time for the denervation procedure in order to reduce side effects that may be caused by occlusion of one or more blood vessels (if any) during the medical procedure.

[0121] Figure 1A1 is a schematic and conceptual illustration of an example system 10 including a denervation therapy delivery device 12 and a therapy generator 14. The denervation therapy delivery device 12 (also referred to as a therapy delivery device 12) may include any device configured to deliver denervation stimulation to a target nerve. The denervation stimulation may include, for example, at least one of the following: RF stimulation, thermal stimulation, cryostimulation, microwave stimulation, ultrasound stimulation, microwave stimulation, radiation stimulation, optical stimulation, or chemical stimulation, and the therapy delivery device 12 may include one or more therapy delivery elements, such as but not limited to at least one of the following: an electrode, an RF probe, a thermal probe, a cryoprobe, a microwave probe, an ultrasound probe, or a catheter configured to deliver a chemical agent to a patient's tissue. In some examples, one or more therapy delivery elements of the therapy delivery device 12 may be incorporated into or mounted on the catheter 20.

[0122] For example, Figure 1B is a schematic and conceptual illustration of an example denervation therapy delivery device 12a including at least one electrode. Figure 1B A plurality of electrodes 16a are shown in FIG. 1 and are collectively referred to as electrodes 16a. Figure 1B In the example shown in , the denervation treatment delivery device 12a includes four electrodes arranged in a spiral configuration. For example, when the device 12a is viewed through an axis passing through the center of the spiral, the electrodes 16a can be arranged to be approximately 90 degrees apart. The electrodes 16a can be spaced any suitable distance from each other, and the spacing between the electrodes 16a and other dimensions of the treatment delivery device 12a can be different based on the specific application in which the treatment delivery device 12a is intended to be used. For example, the maximum width of the treatment delivery device 12a (e.g., along the spiral and in a direction orthogonal to the longitudinal axis of the treatment delivery device 12a) can be 3mm to 8mm, but other widths are also contemplated. In some such examples, the electrodes 16a can be coupled to the generator 14 via electrical leads, such as conductive leads passing through the catheter 20a.

[0123] exist Figure 1A and Figure 1B In the example shown in FIG. 1 , the treatment delivery device 12, 12a may include an elongated shaft having a handle 18 at a proximal region of the proximal portion of the treatment delivery device 12, and a distal portion 20 (20a) extending distally relative to the proximal portion. The treatment delivery device 12, 12a further includes a therapeutic component or treatment portion at the distal portion 20. For example, as Figure 1BAs shown in , the treatment delivery device 12, 12a may include at least one electrode, or an array of two or more electrodes 16a, which is configured to be introduced into a blood vessel (e.g., a renal artery) and advanced along the blood vessel (e.g., a renal artery). In other examples, such as examples where the treatment delivery device 12 is configured to deliver a chemical agent to tissue, the treatment portion may include one or more openings to the lumen of the treatment delivery device 12, 12a, through which the chemical agent can be delivered.

[0124] The therapy delivery device 12, 12a may be configured to be delivered into a patient's body, for example, a blood vessel of the patient, and have a low-profile configuration, such as Figure 1A . When delivered to a target location within or along a blood vessel, the therapy delivery device 12, 12a can be deployed in an expanded state (e.g., a generally helical or spiral configuration) in which one or more therapy delivery elements of the therapy delivery device 12, 12a can contact the blood vessel. In the expanded state, the therapy delivery device 12, 12a can deliver energy at the treatment site and provide therapeutically effective electrical and / or thermally induced denervation. Although in Figure 1B A spiral or helical configuration is shown in the example of FIG, but the electrode 16a may alternatively be arranged along a substantially straight and elongated treatment delivery device 12, such as Figure 1A as shown in , or any other suitable electrode configuration may be employed, such as along an expandable basket-like structure, an outwardly extending finger-like structure, etc.

[0125] In some examples, the treatment delivery device 12 can be placed or converted to a deployed state or arrangement via remote actuation, for example, via an actuator carried by the handle 18, such as a knob, pin, or lever. However, in other examples, the treatment delivery device 12 can be converted between the delivery and deployment states using other suitable mechanisms or techniques. For example, the treatment delivery device 12 can include a shape memory material, thereby enabling the treatment delivery device 12 to be configured to assume a relatively low-profile delivery configuration under the force applied by the outer sheath, and when the sheath is withdrawn, the treatment delivery device 12 can automatically assume the deployed state.

[0126] The distal end of the therapy delivery device 12 may terminate, for example, with an atraumatic rounded tip or cap. Additionally, or alternatively, the distal end of the therapy delivery device 12 may be configured to engage another element of the system 10 or therapy delivery device 12. For example, the distal end of the therapy delivery device 12 may define a channel for engaging a guidewire (not shown) for delivering the therapy device using an over-the-wire ("OTW") or rapid exchange ("RX") technique.

[0127] The treatment delivery device 12 is configured to receive denervation energy from the generator 14 and deliver the energy to adjacent tissue in the form of denervation stimulation. The generator 14 may generate energy that is ultimately transmitted through one or more conductive leads to the electrode 16a. In examples where the denervation stimulation includes non-electrical stimulation (e.g., chemical agents, optical stimulation, or ultrasound), the generator 14 may include a source of non-electrical stimulation (e.g., a reservoir of a pump for pumping a predetermined amount or concentration of a chemical agent at a predetermined flow rate, a light or laser source, a microwave source, a radiation source, or an ultrasound generator).

[0128] In some examples, the generator 14 includes a power source, such as an RF energy generator. The generator 14 is configured to generate energy of a selected form and amplitude for delivery to a target treatment site via the treatment delivery device 12. The generator 14 may be electrically coupled to the treatment delivery device 12 via a cable comprising one or more electrical conductors. At least one power supply wire (not shown) may pass through the wall of the treatment delivery device 12, or through the cavity of the treatment delivery device 12 to the electrode 16a, and transmit the denervation stimulation to the electrode 16a. In some examples, each of the electrodes 16a may be coupled to a corresponding power supply wire. However, in other examples, two or more of the electrodes 16a may be electrically coupled to the same power supply wire.

[0129] A secondary input 21 (e.g., a foot pedal) may be connected (e.g., pneumatically or electrically) to the generator 14 to allow a clinician to initiate, terminate, and optionally adjust various operating characteristics of the generator 14, including, but not limited to, power delivery. The system 10 may also include a remote control device (not shown) that may be positioned in the sterile field and operably coupled to one or both of the treatment delivery device 12 or the generator 14. The remote control device may be configured to allow selective turning on / off of the electrode 16a. In other examples, the remote control device may be placed in the handle 18.

[0130] System 10 may include a programmer 24, referring to Figure 3 The programmer 24 is described in greater detail. The generator 14 may be configured to receive one or more therapy parameter values ​​that the generator uses to generate and deliver the denervation therapy via the programmer 24. In some examples, the generator 14 or programmer 24 may include one or more evaluation or feedback modules for providing feedback to the clinician before, during, and / or after the denervation therapy.

[0131] In some examples, the generator 14 is configured to deliver denervation stimulation via the electrode 16a in a monopolar configuration. For example, the system 10 may include an electrode 22 (or a dispersive electrode) electrically connected to the generator 14 and attached to the patient's body. In other examples, the generator 14 is configured to deliver denervation stimulation via multiple electrodes 16a, 22 in a monopolar configuration.

[0132] Additionally, one or more sensors (not shown), such as one or more temperature sensors (e.g., thermocouples, thermistors, etc.), impedance sensors, pressure sensors, optical sensors, flow sensors, chemical sensors, or other sensors may be positioned near or within the electrode 16a and connected to one or more power supply wires (not shown). For example, a total of two power supply wires may be included, wherein the two wires are capable of transmitting signals from the sensors, and one wire is capable of serving a dual purpose and also delivering energy to the electrode 16a. Alternatively, a different number of power supply wires may be used to deliver energy to the electrode 16a. The sensor may be used by the processor of the treatment generator 14 for, for example, controlling the delivery of denervation therapy, as described in PCT Application No. PCT / US2011 / 057756, published as PCT Application No. WO 2012 / 061161A1, which is incorporated herein by reference in its entirety.

[0133] The generator 14 may be part of a device or monitor that may include a processing circuit system (such as a microprocessor) and a display. In some examples, the functions described elsewhere with reference to the programmer 24 may be performed by the generator 14, and the system 10 may not include a separate programmer. Therefore, the system 10 includes a memory (e.g., in the generator 14 or the programmer 24), which is configured to store one or more tissue characteristics of tissue near the patient's target nerves and blood vessels, and the system 10A also includes a processor coupled to the memory. The processor is configured to determine one or more tissue characteristics of tissue near the target nerves and blood vessels. The processor is configured to generate an estimated volume of influence of denervation therapy delivered by the treatment delivery device 12 disposed in the blood vessel based on one or more tissue characteristics. The processor is configured to generate a GUI that provides information to the clinician to help visualize the denervation therapy and determine the effects of different treatment delivery parameters. In some examples, the GUI includes a graphical representation of tissue near the target nerves and blood vessels and a graphical representation of the estimated volume of influence.

[0134] In some examples, the clinician can use the GUI as a guide to determine a series of target locations and move the treatment delivery device 12 along the series of target locations. The clinician can use a fluoroscopic examination display to verify the movement of the device 12 along the series of target locations. In some cases, at each position in a series of positions, before the generator 14 provides denervation stimulation at that particular position, the clinician may provide input to the processor to confirm to the processor that the device is correctly placed. The processor may cause the generator to deliver stimulation using appropriate ablation parameters for each position in a series of positions. The stimulation causes ablation or damage to the tissue (e.g., the target nerve), but may not directly stimulate the patient's nerve or heart tissue. In some examples, the GUI or another display (e.g., a fluoroscopic examination display) may include a graphical representation of one or more of the series of target locations, and may or may not include a graphical representation of the estimated impact volume.

[0135] Thus, systems and techniques according to the present disclosure may constitute improvements at least to the denervation therapy system 10 itself. For example, example systems and techniques according to the present disclosure may be able to provide more effective denervation therapy. In some examples, denervation therapy may be delivered in a shorter treatment time, for example, due to a relatively more even distribution of treatment delivery locations. Further, systems and techniques according to the present disclosure may reduce or avoid the need for trial-and-error by clinicians in determining, for example, placement, positioning, orientation, and denervation parameters, because the system may indicate to the clinician appropriate placement, positioning, orientation, and denervation therapy parameters.

[0136] Figure 2 yes Figure 1A Schematic and conceptual illustration of the deployment of an example system 10 for delivering denervation therapy. The therapy delivery device 12 provides access to the renal plexus RP through an intravascular pathway P, such as a percutaneous access site in the femoral artery (shown), brachial artery, radial artery, or axillary artery to a target treatment site within a corresponding renal artery RA. As shown, a portion of the proximal portion of the shaft is exposed outside the patient's body, adjacent to the handle 18. By manipulating the handle 18 and the external portion of the therapy delivery device 12 from outside the intravascular pathway P, the clinician can advance the distal portion 20 through the sometimes tortuous intravascular pathway P and remotely manipulate the distal portion 20.

[0137] Image guidance can be used to assist the clinician's manipulation, for example, computed tomography (CT), fluoroscopy, intravascular ultrasound (IVUS), optical coherence tomography (OCT) or another suitable guidance modality, electrical impedance tomography (EIT) or a combination thereof. Further, in some examples, image guidance components (e.g., IVUS, electrode impedance tomography or OCT) can be incorporated into the treatment delivery device 12 itself. After the treatment delivery device 12 is positioned at the desired position in the renal artery RA, the treatment delivery device 12 can be radially deployed or otherwise deployed using a handle 18 or other suitable device until the electrode 16a is in stable contact with the inner wall of the renal artery RA. The energy from the electrode 16a is then purposefully applied to the tissue to cause one or more desired neuromodulatory effects on the local area of ​​the renal artery and the adjacent area of ​​the renal plexus RP, which is closely located within the adventitia of the renal artery RA, adjacent to the adventitia of the renal artery RA, or adjacent to the adventitia of the renal artery RA. The purposeful application of energy can achieve denervation along all or at least a portion of the renal plexus RP.

[0138] The denervation effect generally depends at least in part on power, time, contact between the electrode 16a and the vessel wall, and blood flow through the vessel. The denervation effect may be accompanied by other effects, such as thermal ablation, and non-ablative thermal changes or damage (e.g., via continuous heating and / or resistive heating). The desired thermal heating effect may include raising the temperature of the target nerve fibers to above a desired threshold to achieve non-ablative thermal changes, or to above a higher temperature to achieve ablative thermal changes. For example, the target temperature may be higher than body temperature (e.g., approximately 37° C.) but less than approximately 45° C. for non-ablative thermal changes, or the target temperature may be approximately 45° C. or higher for ablative thermal changes. The desired non-thermal denervation effect may include changing the electrical signals transmitted in the nerve, for example, causing the electrical signals to attenuate.

[0139] Exposure to thermal energy (e.g., heat) at temperatures above body temperature (approximately 37°C) but below approximately 45°C may cause thermal changes via moderate heating of target neural fibers or moderate heating of the vasculature that perfuses the target fibers. In examples where the vasculature is affected, the target neural fibers may be denied perfusion, resulting in neural tissue necrosis. For example, this may cause non-ablative thermal changes in the fibers or structures. Exposure to temperatures greater than approximately 45°C or heat greater than approximately 60°C may cause thermal changes via substantial heating of the fibers or structures. For example, such higher temperatures may thermally ablate the target neural fibers or vascular structures. In some patients, temperatures that achieve thermal ablation of the target neural fibers or vascular structures may be desirable, but are below approximately 90°C, or below approximately 85°C, or below approximately 80°C and / or below approximately 75°C. Regardless of the type of thermal exposure utilized to induce thermal neuromodulation, a reduction in renal sympathetic nerve activity ("RSNA") is expected to occur. Reference Figures 10 to 13B Relevant patient anatomy and physiology are described in greater detail.

[0140] In some examples, the electrode 16a may be near, adjacent to, or carried by the support structure (e.g., adhered to, threaded over, wrapped around, and / or crimped to the support structure). The proximal end of the support structure may be coupled to the distal portion 20 of the treatment delivery device 12 via a coupling (not shown). The coupling may be an integral component of the elongated shaft (i.e., may not be a separate piece), or the coupling may be a separate piece, such as a collar (e.g., a radiopaque band) wrapped around the outer surface of the elongated shaft for securing the support structure to the elongated shaft. However, in other examples, the support structure may be associated with the elongated shaft using another arrangement and / or different features.

[0141] When multiple electrodes 16a are provided, the electrodes 16a can deliver power independently (i.e., can be used in a monopolar manner) simultaneously, selectively, or sequentially, and / or can deliver power between any desired combination of these elements (i.e., can be used in a bipolar manner). Further, the clinician, generator 14, or programmer 24 optionally can select which electrode(s) 16a to use for power delivery in order to form (multiple) customized lesions having various predetermined shapes or patterns within the renal artery. Selecting a specific electrode 16a for delivering denervation stimulation to tissue is an example of a therapy delivery parameter value that the programmer 24 can determine using the computer modeling techniques described herein.

[0142] The operation of therapy delivery device 12 and generator 14 may be controlled by programmer 24 based on the estimated volume of effect of the denervation therapy. For example, programmer 24 may determine one or more therapy parameters of a therapy procedure for achieving a predetermined level of denervation in a target area of ​​the patient.

[0143] Figure 3 is a schematic and conceptual illustration of an example programmer 24 coupled to a medical imaging system 46 and an example therapy delivery device 12. Although reference is made to Figure 3 The programmer 24 of FIG. 2 describes various circuit systems, algorithms, modules, and functions, but in other examples, the generator 14 or other medical device may include the features and perform the functions described with reference to the programmer 24 .

[0144] Programmer 24 includes processor 25, user interface 26, and memory 28. Memory 28 includes computer-readable instructions that, when executed by processor 25, cause programmer 24 to perform various functions. Processor 25 may include any one or more microprocessors, controllers, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or equivalent discrete or integrated digital or analog logic circuitry, and the functionality attributed to processor 25 herein may be implemented as software, firmware, hardware, or any combination thereof.

[0145] The memory 28 may include any volatile, nonvolatile, magnetic, optical, or electrical medium, such as random access memory (RAM), read-only memory (ROM), nonvolatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, or any other digital medium. The memory 28 may store any suitable information, including patient identification information, and information for generating one or more treatment programs that the generator 14 uses to generate and deliver denervation therapy to the patient. For example, the memory 28 may store one or more of the following in separate memories or separate areas within the memory 28: a patient anatomy reconstruction 30, a computer model 32, a treatment program 34, a stimulation algorithm 36, and operating instructions.

[0146] Each treatment program 34 defines a particular treatment program in terms of corresponding values ​​of denervation stimulation parameters, such as the one or more electrodes 16a used to deliver stimulation to the patient, electrode polarity (if applicable), duty cycle, current or voltage amplitude and / or frequency, or appropriate non-electrical parameters in examples where the denervation stimulation includes non-electrical stimulation. Memory 28 may also store operating instructions (which processor 25 uses to control the operation of programmer 24), and may include instructions for measuring the impedance of electrode 16a and / or determining the placement and orientation of electrode 16a along a blood vessel.

[0147] The generator 14 is configured to receive one or more treatment programs 34 from the programmer 24 and apply denervation treatment parameter values, such as amplitude, duty cycle, and frequency, specified by the received one or more treatment programs 34 for generating denervation stimulation. For example, the generator 14 may control the stimulation circuit system 38 to generate a denervation stimulation signal according to a particular treatment program and deliver the denervation stimulation signal via the treatment delivery device 12. The stimulation circuit system 38 may be electrically coupled to one or more conductors of the treatment delivery device 12 using any suitable technology. For example, the generator 14 may include a switching circuit system configured to switch the stimulation generated by the stimulation circuit system 38 across different electrodes, or the generator 14 may include multiple energy sources for driving more than one electrode at a time.

[0148] In some examples, the generator 14 may include, for example, a sensing circuit system 40 coupled to the therapy delivery device 12, for example, for receiving electrical measurements, feedback, or signals (e.g., impedance), and a processor of the generator 14 may automatically control the delivery of the denervation stimulation signal via the therapy delivery device 12.

[0149] In some examples, the system 10 may include one or both of a drive circuit system 41 or a drive unit 48 that is ultimately coupled to the therapy delivery device for controlling one or more of the movement, position, or orientation of the therapy delivery device 12 along a blood vessel in which the therapy delivery device 12 is disposed. For example, the drive unit 48 may include a stepper motor, a servo motor, or a suitable motor, or a magnetic track, or any other suitable mechanism for advancing, retracting, rotating, and repositioning the therapy delivery device 12 along a blood vessel. The drive circuit system 41 may control the operation of the drive unit 48, for example, by amplifying or sending control signals from the processor 25 to the drive unit 48. In some examples, the drive circuit system 41 may receive feedback signals from the drive unit 48 indicating the current position or orientation of the therapy delivery device 12 and the degrees of freedom or resistance to movement of the therapy delivery device 12, and such feedback signals may be sent to the processor 25 for ultimate control of the movement and positioning of the therapy delivery device 12.

[0150] The user (clinician or patient) can interact with the processor 26 through the user interface 25. The user interface 26 may include: a display, such as a liquid crystal display (LCD), a light emitting diode (LED) display, or other screen to present information related to the stimulation therapy; and buttons or pads for providing input to the programmer 24. In examples where the user interface 26 requires a 3D environment, the user interface may support a 3D environment, such as a holographic display, a stereoscopic display, an autostereoscopic display, a head-mounted 3D display, or any other display capable of presenting 3D images to the user. The buttons of the user interface 26 may include an on / off switch, plus and minus buttons for zooming or navigating through options, a selection button for selecting or storing inputs, and a pointing device, such as a mouse, a trackball, or a stylus. Other input devices may be a scroll wheel for scrolling through options, or a touch pad for moving a pointing device on the display. In some examples, the display may be a touch screen that enables the user to select options directly from the display screen.

[0151] In some examples, the programmer 24 may include a telemetry module that may support wired or wireless communication between the programmer 24 and the generator 14 or another computing device under the control of the processor 125. A clinician or another user may interact with the programmer 24 for generating and / or selecting a treatment program 34 for delivery via the treatment delivery device 12. In some examples, the programmer 24 may allow the clinician to define a target volume of influence and generate appropriate treatment delivery parameter values ​​for achieving the desired volume of influence. The programmer 24 may be used to present an anatomical region to the clinician via the user interface 26, select a treatment program 34, generate a new treatment program 34 by manipulating the estimated volume of influence on the computer model 32 or GUI presented on the user interface 26, and communicate the selected treatment program 34 to the generator 14.

[0152] Programmer 24 may include a power source for delivering operating power to the components of programmer 24. The power source may include at least one battery and a power generation circuit for generating operating power. In some examples, the battery may be rechargeable to allow extended operation. Recharging may be accomplished by proximal inductive interaction or electrical contact with the circuit system of a base station or recharging station. In other examples, primary batteries (e.g., nickel-cadmium- or lithium-ion batteries) may be used. In addition, programmer 24 may be directly coupled to an AC power source, such as in the case of some computing devices, such as a personal computer. The power source may include circuitry for monitoring the power remaining in the battery. In this way, when the battery needs to be replaced or recharged, user interface 26 may provide a current battery level indicator or a low battery level indicator. In some cases, the power source may be able to estimate the remaining time of operation using the current battery.

[0153] In some examples, programmer 24 may be communicatively coupled to medical imaging system 46, or may otherwise receive one or more medical images of a patient from medical imaging system 46. Medical imaging system 46 may be configured to generate a medical image of a region of a patient that includes a target nerve (e.g., intended to be denervated) and, in some cases, a corresponding blood vessel. The corresponding blood vessel may be, for example, an artery or another blood vessel through which a treatment delivery device may access the target nerve. The one or more medical images generated by medical imaging system 46 may be stored by programmer 24 in memory 28, or otherwise used by processor 25, for generating a digital reconstruction 30 of the patient's anatomy. The medical image may be any medical image that provides sufficient resolution for identifying tissue regions to be avoided (e.g., specific muscles, lymph nodes, other vascular veins / arteries, the kidney itself, the digestive tract, or other anatomical features or tissues).

[0154] In some cases, the memory 28 of the programmer 24 or another device (e.g., a remote device) may store a plurality of medical images of the patient, which may be, for example, a plurality of medical images of the same or nearly the same region of the patient. In some cases, if there is a relatively large time interval between denervation sessions (e.g., on the order of weeks, months, or even years), the clinician may choose to use the medical imaging system 46 to generate one or more updated medical images of the patient, or otherwise acquire updated medical images of the patient, and update one or more treatment programs used by the generator 14 based on the one or more updated medical images. In some examples, the plurality of medical images may include any suitable available medical images of the patient region, for example, images of the patient region acquired for treatments other than denervation therapy. The anatomical structure and / or tissue characteristics of a particular patient may change over time, such as due to weight gain, weight loss, etc.

[0155] In some examples, the medical imaging system 46 includes at least one of: a fluoroscopic examination system, a computer-assisted tomography (CAT) scanning system, a magnetic resonance imaging (MRI) system, a positron emission tomography (PET) scanning system, an electrical impedance tomography (EIT) system, an ultrasound system, or an optical imaging system. In some examples, EIT can be used to identify the rough location of extravascular structures such as nerves, fat, renal veins, etc. In some examples, locating these or other structures in three-dimensional space (e.g., by EIT) can improve the digital reconstruction 30 or computer model 32. The processor 25 can be configured to develop a computer model 32 based on the patient's anatomical structure reconstruction 30. In some examples, the computer model 32 includes a finite element model. In some examples, the digital reconstruction 30 includes a three-dimensional (3D) reconstruction. The processor 25 can use one or both of the digital reconstruction 30 or the computer model 32 to determine an estimated impact volume of the denervation treatment, and determine one or more treatment procedures 34 based on the estimated impact volume, as described in reference Figure 4 , Figure 6 and Figure 7 The processor 25 may further be used to deliver and monitor the delivery of denervation therapy by the generator 14 based on the treatment program 34, as described in reference Figure 4 , Figure 6 and Figure 7 Description.

[0156] Figure 4 is a flow chart illustrating an example technique for delivering denervation therapy. Figure 1A , Figure 1B , Figure 2 and Figure 3 Example system description Figures 4 to 7 However, any suitable system or device may be used to perform Figures 4 to 7 In some examples, Figure 4 An example technique includes determining, by processor 25, one or more tissue properties of tissue near target nerves and blood vessels (50). The tissue properties may include, but are not limited to, one or more of the following: electrical impedance, thermal conductivity, acoustic impedance, chemical diffusion rate, optical transmittance, or density of the tissue. The tissue may include blood, muscle, fat, nerves, body fluids, bone, kidney, calcium deposits, or any suitable tissue. In some examples, processor 25 may determine the tissue properties by generating a computer model 32 based at least on a digital reconstruction 30 including the target nerves and blood vessels, such as reference Figure 5 As described.

[0157] The processor 25 may generate at least one estimated volume of impact (52) of a denervation therapy delivered via a therapy delivery device 12 disposed within a blood vessel according to one or more corresponding treatment procedures based on one or more tissue characteristics. For example, based on thermal and electrical conductivities associated with different tissue types identified according to the computer model 32 of the area of ​​the patient, the processor 25 may determine a volumetric range to which energy or denervation stimulation may be electrically or thermally conducted from the electrode 16a (or generally from the location and orientation of the therapy delivery elements of the therapy delivery device 12, 12a). As an example, the processor 25 may determine an estimated propagation of an RF signal having a predetermined frequency and amplitude, and estimate the propagation of thermal waves based on tissue properties such as conductivity and density. As another example, based on the chemical diffusion rate of the tissue indicated by the computer model 32 of the area of ​​the patient, the processor 25 may determine a volumetric range of chemical stimulation caused by the delivery of a chemical agent by the therapy delivery device 12, 12a.

[0158] In some examples, the computer model 32 may take into account the blood flow rate in one or more blood vessels in the area of ​​the patient. For example, the blood flow rate in a blood vessel (e.g., a renal artery) may affect the volume of influence obtained by delivering a stimulus by the treatment delivery device 12. For example, a higher blood flow rate may result in relatively faster heat dissipation, resulting in a smaller volume of influence for a given denervation stimulus compared to the volume of influence associated with a lower blood flow rate. In some examples, the computer model 32 may include blood flow rates at or near the target tissue site, which may help increase the efficacy, efficiency, or both of the denervation therapy delivered by the treatment delivery device 12, 12a compared to the denervation therapy delivered in an ad hoc manner without the assistance of the computer model 32. The patient-specific anatomical structure may include, for example: the location and relative arrangement of different anatomical structures of the patient (e.g., organs, blood vessels, target tissue sites, etc.), and the size of one or more blood vessels, which may correspond to the blood flow rate through the blood vessel, and therefore to the thermal conductivity and / or electrical conductivity of the blood vessel.

[0159] In some examples, the computer model 32 may also take into account the extent of contact between electrodes or other energy delivery elements of the therapy delivery devices 12, 12a and the patient's tissue in order to estimate the volume of influence of one or more denervation stimuli.

[0160] The processor 25 may determine the estimated volume of influence using any suitable technique, including but not limited to: a finite element model, or another algorithm that numerically represents how different stimuli affect different types of tissue. Whether the stimulus is electrical, thermal, chemical, optical, or other types of stimulation, the estimated volume of influence may indicate the extent of the denervation stimulus and may indicate the activity of the neural and non-neural tissues affected by the denervation stimulus. For example, the processor 25 may determine that a lesion will not be formed in tissue outside the estimated volume of influence, but may be formed within the estimated volume of influence. Thus, in some examples, the estimated volume of influence includes a lesion, such as a denervation lesion. In some examples, one or more volumes of influence or lesion may extend circumferentially around a vessel, such as around an axis along the vessel greater than about 180°, or around the axis greater than about 270°, or around the axis greater than about 300°, or around the vessel substantially 360°. In some examples, the periphery of the vessel may have a substantially circular cross-section perpendicular to the axis. In other examples, the cross-section may be non-circular, such as any closed curve. In some examples, the volume of influence or lesion may extend along a substantially circular path around the axis. In other examples, the volume of impact or damage may extend along a non-circular path, a closed path, or an open path (eg, a spiral path) about an axis.

[0161] In some examples, processor 25 may determine two or more estimated volumes of influence based on respective treatment procedures. For example, processor 25 may generate a first estimated volume of influence for a first denervation treatment delivered by treatment delivery device 12 according to a first treatment procedure of treatment procedures 34, and determine a second estimated volume of influence for a second denervation treatment delivered by treatment delivery device 12 according to a second treatment procedure of treatment procedures 34. The second treatment procedure includes at least one treatment parameter value that is different from a corresponding parameter value of the first treatment procedure.

[0162] In some examples, the processor 25 may determine a plurality of treatment programs that each provide effective results for a specific patient, for example, due to similar targeting of renal nerves or other nerves or target tissue sites by denervation stimulation. However, the results of delivering denervation therapy according to different treatment programs may differ from each other in one or more ways. For example, some treatment programs may define denervation stimulation that requires more power to generate compared to one or more other treatment programs, thereby making some treatment programs more efficient (e.g., in terms of power usage) than other treatment programs. As another example, some treatment programs may cause more non-target tissue damage compared to one or more other treatment programs. Therefore, the processor 25 may select a treatment program not only based on the damage of the estimated target tissue site, but also based on one or more other factors, such as the power consumed during the treatment session, the impact on non-target tissue sites, etc. In some examples, the processor 25 may sort the list of treatment programs based on one or more of these other factors (e.g., sorting in ascending or descending order based on power consumption, non-target tissue sites affected by treatment, etc.), and present the sorted list of treatment programs to the user via the display of the user interface 26. Processor 25 may then select one or more therapy programs for controlling delivery of therapy to the patient in response to patient input, or automatically based on a first one or more predetermined numbers of therapy programs in the ranked list.

[0163] In some examples, the processor 25 may generate a plurality of treatment programs (which may differ from each other in at least one treatment parameter value for a given treatment parameter) and determine a plurality of volumes of influence, each of which is associated with a corresponding treatment program in the plurality of treatment programs. The processor 25 may determine a volume of influence in the plurality of volumes of influence, for example, at least one volume of influence that extends to the tissue of interest while avoiding non-target sites (e.g., predetermined side effect sites). Based on the at least one volume of influence, the processor 25 may select a treatment program in the plurality of treatment programs for delivering denervation therapy to the patient. The processor 25 may control the generator 14 to generate and deliver the denervation therapy according to the treatment delivery parameters defined by the selected treatment program, generating at least one volume of influence at the target tissue site, thereby causing the at least one volume of influence to not affect or extend to the non-target tissue site.

[0164] In some examples, the processor 25 may generate multiple treatment programs (which differ from each other at least in the location of the volume of influence along the blood vessel). For example, the processor 25 may generate multiple treatment programs delivered at multiple locations along the blood vessel, for example, six, nine, twelve, or any suitable number of locations along the length of the blood vessel. The processor 25 may determine multiple volumes of influence, each of which is associated with a corresponding location in the multiple locations along the blood vessel. In some examples, two or more volumes of influence along the blood vessel may overlap in volume. In some examples, the processor 25 may select a treatment program that implements a relatively simple therapeutic impact pattern (e.g., ablation) along the blood vessel. For example, the simple pattern may be the most effective, or the simplest to deliver for the clinician, or may result in relatively minimal side effects along the blood vessel in non-target tissue sites along the blood vessel, or otherwise obtain a given pattern of treatment delivery along the blood vessel. In some examples, the processor 25 may select a treatment program that generates a pattern of the volume of influence along the blood vessel for a given treatment delivery device, for example, a given type or configuration or orientation of a catheter or electrode along the treatment delivery device. In some examples, a given therapy delivery device may include a catheter defining a helix or spiral-shaped portion, and three, four, or more electrodes or other suitable therapy delivery elements that simultaneously deliver therapy along the helix or spiral-shaped portion.

[0165] In some examples, processor 25 may select a treatment procedure that generates different volumes of influence (e.g., extending to different geometric volumes) at different locations along the vessel. A specific volume of influence at a specific location may correspond to, for example, the location of a target tissue site (e.g., a renal nerve) relative to the treatment delivery device. In some examples, the treatment procedure may generate a smaller volume of influence at one or more locations along the vessel and a larger volume of influence at other locations along the vessel. In some examples, the volume of influence may gradually increase in volume along the vessel, or may gradually decrease in volume.

[0166] In some examples, processor 25 may select a plurality of treatment programs, each of the plurality of treatment programs being associated with a location in a different location along the blood vessel. Different treatment programs in the plurality of treatment programs may differ in one or more treatment parameters at different locations. In some examples, respective magnitudes of treatment parameters of respective treatment programs may gradually increase along the blood vessel, or gradually decrease along the blood vessel.

[0167] In some examples, processor 25 generates GUI 26 (54) that includes a graphical representation of tissue near the target nerves and blood vessels and a graphical representation of the estimated volume of impact. GUI 26 can provide information to the clinician to relatively quickly determine the therapeutic effect of a particular treatment procedure for a particular patient, which is not possible with existing renal denervation treatment programming that does not provide such patient-specific modeling.

[0168] In addition to or in lieu of generating the GUI 26, the processor 25 may determine one or more treatment parameter values ​​for effective denervation therapy delivery based on the estimated volume of influence (56). For example, the processor 25 may select one or more of the modeled treatment programs 34 based on the resulting estimated volume of influence (52). The treatment parameter values ​​may include, for example, at least one of an electrical signal parameter, a thermal signal parameter, an ultrasound signal parameter, a microwave signal parameter, or a chemical dose parameter. In some examples, the treatment parameter values ​​may include, for example, a corresponding location in the patient's body for delivering denervation stimulation. The processor 25 may select the one or more treatment parameter values ​​using any suitable one or more criteria. For example, in some cases, the processor 25 determines the one or more treatment parameter values ​​by at least selecting one or more treatment parameter values ​​(or treatment programs) that are determined to result in damage to the target nerve and avoid damage to a predetermined side effect area. In other examples, the processor 25 determines the one or more treatment parameter values ​​by at least selecting one or more treatment parameter values ​​(or treatment programs) that are determined to avoid damage to a predetermined side effect area without necessarily resulting in estimated damage to the target nerve.

[0169] In the example where the processor 25 generates an estimated volume of influence, the processor 25 determines one or more treatment parameter values ​​for denervation therapy delivery by selecting at least a subset of the plurality of modeled treatment procedures (e.g., one or more modeled treatment procedures). For example, in the example above where the processor 25 generates an estimated volume of influence for each of the first treatment procedure and the second treatment procedure based on the respective first and second estimated volumes of influence, the processor 25 may select a treatment procedure associated with a volume of influence encompassing a target nerve for denervation and / or a treatment procedure associated with a volume of influence that results in avoiding damage to a predetermined side effect region (e.g., a tissue or organ that is not sought to be damaged).

[0170] In some examples, the processor 25 may generate a GUI 26 that ranks the treatment programs 34 based on the determined efficacy (e.g., obtaining damage to the target tissue and / or avoiding damage to the side effect area), or the clinician may otherwise select one of the treatment programs 34. For example, the processor 25 may associate each stored treatment program 34 with a numerical score based on the associated estimated volume of influence, the score indicating, for example, the amount of overlap of the estimated volume of influence with the target nerve and / or the amount of overlap with the side effect area. The processor 25 may then rank the treatment programs 34 in ascending or descending order based on the score. The clinician may then quickly review the ranked list of treatment programs to determine which one or more treatment programs should be used to program the generator 14.

[0171] In some examples, processor 25 may control generator 14 to generate and deliver denervation therapy to the patient based on the determined one or more therapy parameter values ​​34 (58). For example, processor 25 may transmit one or more selected therapy programs 34 to generator 34 via wired or wireless communication, or directly control stimulation circuit system 38 to generate and deliver denervation therapy based on the selected therapy program 34.

[0172] In some examples, the example techniques further include generating, by the processor 25 and based on the estimated volume of influence, an index position of the treatment delivery device 12 in the patient's body, and associating the index position with a specific treatment procedure. For example, the index position can be a position along a blood vessel (or along the axis of the treatment delivery device 12), and the index position can be a position of a treatment delivery element (e.g., electrode 16a) of the treatment delivery device 12 relative to the blood vessel or another anatomical landmark or landmark on the treatment delivery device 12. The index position can be used to determine the extent to which the treatment delivery device 12 has been advanced into the blood vessel, or otherwise used to determine the proximity of one or more treatment delivery elements (e.g., electrode 16a) of the treatment delivery device 12, 12a. For example, the GUI 26 or another display may include a graphical representation of one or more index positions. In some examples, the GUI 26 or another display may include a graphical representation of one or more index positions without including a graphical representation of the volume of influence. In some examples, the drive unit 48 can advance or retract the treatment delivery device 12, 12a along the blood vessel by monitoring the index position (e.g., an index position on the treatment delivery device 12 that can be determined outside the blood vessel).

[0173] The processor of drive unit 48 may use any suitable technique to control the position of treatment delivery device 12. For example, drive unit 48 may include an optical unit that monitors a visible marker on treatment delivery device 12 for determining the relative position of treatment delivery device 12 relative to an entry point into the patient. As another example, treatment delivery device 12 may include a magnetic marker, and drive unit 48 may use the magnetic marker (e.g., the magnitude of a magnetic field generated by the magnetic marker and sensed by a sensor of drive unit 48) to determine the relative position of treatment delivery device 12 (e.g., relative to programmer 24). In some examples, treatment delivery device 12 may include a radiopaque or x-ray marker detectable under fluoroscopy, which a clinician or drive unit 48 may align with a predetermined registration marker superimposed on a display of a fluoroscopy or other medical image. The radiopaque marker superimposed on the displayed medical image may enable a clinician to manually assess the positioning of treatment delivery device 12.

[0174] In some examples, the processor 25 may generate a GUI that includes an image (such as a fluoroscopic image of an area of ​​a patient), and may superimpose a marker on the image to show the clinician where the index position is located relative to the patient's anatomy. The processor 25 may superimpose one marker at a time to help guide the clinician to the next location for delivering denervation stimulation, or may superimpose multiple markers at a time. For example, the clinician may compare the superimposed marker with a marker indicating the index position (e.g., a radiopaque marker on the treatment delivery device 12). The clinician may use this information to manually guide the treatment delivery device 12 to different locations in the patient's body during a medical procedure. In other examples, the processor 25 may communicate with a fluoroscopic imaging system or another imaging system, which may then superimpose one or more markers on the patient's medical image, similar to the aforementioned examples.

[0175] In some examples, the target nerve or nerve bundle may not be observable by imaging. In some such examples, the processor 25 or clinician may attempt to lesion the target area (where the nerve may be suspected or predicted to be present) without causing adverse effects to non-target tissue. In some such examples, the processor 25 or clinician may determine a treatment procedure that increases the overall lesion volume while reducing the number of sites of treatment delivery, such as along a blood vessel.

[0176] As discussed above, in some examples, processor 25 generates a computer model of a region of a patient, wherein the computer model defines a spatial representation of tissue in the region, including corresponding tissue properties (e.g., thermal conductivity, electrical conductivity, density, etc.) Processor 25 may generate the computer model using any suitable technique. Figure 5is a flow chart illustrating an example technique for generating a computer model of a region of a patient.

[0177] exist Figure 5 In the example of , processor 25 receives at least one medical image (51) of an area of ​​a patient from medical imaging system 46. Any suitable imaging modality may be used for the medical images, examples of which are described above. Based on the at least one image, processor 25 may identify different types of tissue in the at least one image (53). Example tissue types include, but are not limited to: bone, tendon, muscle, fat, lymph node, blood vessel, and / or organ. As another example, example tissue types may be based solely on tissue properties, such as, but not limited to: thermal or electrical conductivity of the tissue, density of the tissue, chemical diffusion rate of the tissue, acoustic or ultrasonic parameters (e.g., speed of sound or attenuation velocity), etc., or any combination thereof.

[0178] For example, processor 25 may identify a predetermined tissue type in at least one image based on the location, size, or one or more visual characteristics of the image (e.g., the depth of the color of the image) or in coordination with the expected density of different tissue types. As another example, processor 25 may display a predetermined tissue type in at least one image via user interface 26 ( Figure 3 ) receives user input identifying different tissue types in the images. For example, a user may provide input outlining different sub-regions of tissue types and identifying the tissue types, such as by assigning specific tissue types to the different sub-regions. However, in some examples, processor 25 may also perform this operation automatically, such as by using image processing techniques (e.g., edge detection) to find boundaries between different tissue types. By identifying different types of tissue in at least one image, processor 25 may generate a map of a region of the patient that indicates the relative location and type of tissue near target nerves and associated blood vessels.

[0179] Processor 25 may assign tissue properties corresponding to different types of tissue associated with known tissue types (55). For example, processor 25 may assign corresponding thermal conductivity and / or electrical conductivity values, optical transmittance, or chemical diffusivity values ​​associated with the corresponding tissue types to different identified tissue types within the medical image. In some examples, one or more of the conductivity or electrical conductivity and tissue density of different tissue types may be common to patients, or at least common to certain categories of patients (e.g., tissue properties of newborns may be similar to each other, while tissue properties of elderly patients may be similar to each other). Processor 25 may store in memory 28 of programmer 24 ( Figure 3 ) or another device to associate different tissue types with corresponding tissue characteristics.

[0180] In addition to or in lieu of at least one image (e.g., an electronic map of a patient region), the processor 25 may generate a computer model using an impedance map determined by a plurality of electrodes introduced into a region of the patient. In some examples, a clinician may specify a tissue type, and the processor 25 may assign corresponding tissue properties (e.g., thermal and electrical conductivity and density) to the tissue type identified by the clinician. In this way, by combining the tissue properties of different tissue types identified in at least one image with the spatial relationship, the processor 25 may generate a computer model 32 representing the tissue properties at different locations within the patient region in the image. The computer model 32 may be, for example, a digital reconstruction of a region of the patient.

[0181] In some examples, processor 25 may process multiple images to generate a 2D or 3D computer model 32. The electronic maps and / or images may be registered to one another using any suitable means, such as by aligning anatomical landmarks (e.g., bony landmarks) visible in the images and / or maps.

[0182] Figure 6 is a flow chart illustrating another example technique for delivering denervation therapy. Figure 6 The technique shown in can be Figure 4 A more specific example of the technique. Figure 6 In some examples of the techniques shown in FIG. 1 , processor 25 generates a computer model 32 (60) based on a digital reconstruction 30 of a region of a patient. The region includes target nerves and blood vessels. Computer model 32 defines a spatial representation of one or more tissue properties in the region. Processor 25 can generate computer model 32 (e.g., using relative Figure 5 Computer model 32 may be determined by retrieving an already generated computer model 32 from memory 28 of programmer 24 or from the memory of another device) or by using the techniques described above.

[0183] The processor 25 subjects the computer model 32 to a plurality of digital representations of denervation stimuli (64). For each of the digital representations of the denervation stimuli, the processor 25 simulates delivery of the corresponding denervation stimulus to a digital reconstruction of the patient's tissue by (a digital representation of) the treatment delivery device 12 in a corresponding predetermined orientation and at a corresponding predetermined position along a blood vessel. The processor 25 determines a corresponding response state of the computer model 32 for each of the digital representations of the denervation stimuli (66). For example, the processor 25 may generate an estimated volume of influence based on the amplitude, orientation, and direction of the denervation stimulus and based on tissue properties of tissue adjacent to the target nerves and blood vessels (as represented in the computer model 32). The response state may indicate how far the denervation effect of the denervation stimulus is expected to propagate from the treatment delivery device 12 within the patient's body, given the tissue properties of the tissue near the treatment delivery element of the treatment delivery device 12.

[0184] exist Figure 6 In the technique shown in , the processor 25 generates an estimated volume of influence expected to result from delivery of the denervation therapy delivery device 12 according to a particular treatment procedure by subjecting the computer model 32 to digital representations of a plurality of denervation stimuli and determining the response states of the computer model 32 to the respective denervation stimuli.

[0185] The processor 25 may select a denervation stimulus for delivering treatment to the patient based on the determined response state. For example, the processor 25 may determine the activity of the target nerve based on the response state, and may compare the activity to a threshold value (68). In some examples, the processor 25 may determine the activity based on the temperature that the target nerve or adjacent tissue is expected to reach and the time period that the target nerve or adjacent tissue is expected to maintain at that temperature. For example, if the expected temperature is relatively high, a shorter duration may be sufficient to affect the activity. If the activity of the nerve is below the threshold, the response state may indicate denervation of the target nerve (because the activity of the nerve decreases below the threshold). In some such examples, the processor 25 may select the at least one denervation stimulus in response to determining that the corresponding response state associated with the selected at least one denervation stimulus indicates that the activity of the nerve is below the threshold (70). In such examples, the processor 25 may store the treatment program for generating the denervation stimulus in the treatment program 34 as an effective treatment program, or by storing the treatment program as a new treatment program added to the treatment program 34. In some examples, processor 25 may associate a treatment program with a particular target nerve, such that if the target nerve is to be denervated, processor 25 or another device may select the treatment program. In some examples, the target nerve may be a member of a nerve bundle, and the treatment program may be associated with the nerve bundle.

[0186] In some examples, the area of ​​the patient includes at least one non-target non-neural tissue. In some such examples, in addition to or in lieu of the inactivity or low activity of the target nerve, a sufficiently high activity of the non-target tissue (e.g., non-neural tissue or organ) may be sought. In some such examples, the corresponding response state associated with the selected at least one denervation stimulus may indicate that the activity of the non-target non-neural tissue is greater than a threshold. Therefore, in some examples, the processor 25 selects the at least one denervation stimulus in response to determining that the corresponding response state associated with the selected at least one denervation stimulus indicates that the activity of the non-target non-neural tissue is higher than a threshold. The processor 25 may store the treatment program for generating the denervation stimulus in the treatment program 34 as an effective treatment program, or by storing the treatment program as a new treatment program added to the treatment program 34. In some examples, the processor 25 may associate the treatment program with a specific target nerve, thereby allowing the processor 25 or another device to select the treatment program if the target nerve is to be denervated.

[0187] Processor 25 may subsequently use one or more selected denervation stimuli (or resulting treatment programs) to control the delivery of denervation therapy by generator 14. For example, processor 25 may control generator 14 to deliver denervation therapy to an area of ​​the patient via treatment delivery element 12 in accordance with the denervation stimuli (or resulting treatment programs) (72).

[0188] While a clinician may deploy and manipulate the location, orientation, and initiation of denervation stimulation delivery via therapy delivery device 12, in some examples, programmer 24 may control or assist the clinician in automatic or semi-automatic positioning, orientation, or triggering of the therapy delivery device.

[0189] Figure 7 is a flow chart illustrating an example technique for controlling the position of a therapy delivery device 12 within a patient during a medical procedure. Memory 28 of programmer 24 or a memory of another device may store a plurality of indexed positions of therapy delivery device 12. The indexed positions may correspond to positions (e.g., relative to certain known landmarks) at which therapy delivery elements of device 12 may be positioned along the length of a vessel for providing an even distribution of denervation stimulation. In addition, or alternatively, the indexed positions may correspond to a particular therapy procedure selected for the corresponding location to provide a desired volume of impact. As discussed above, because of different tissue characteristics at different locations along a vessel, the denervation therapy parameter values ​​required to generate a volume of impact that results in a desired therapeutic effect may be different based on the location within the patient. Figure 7The techniques may help the system 10 provide more efficient and effective denervation therapy in a shorter amount of time by associating known locations with corresponding treatment programs that have been determined (using the computer model 32) to be likely to result in effective treatment delivery to the patient.

[0190] according to Figure 7 , the processor 25 controls the surgical device to move the treatment delivery device 12 to a predetermined position within the blood vessel (80). For example, the processor 25 may send one or more control signals to the drive unit 48 via the drive circuit system 41 or otherwise, and the drive unit 48 may engage the treatment delivery device 12 and cause the treatment delivery device 12 to advance, retract, or rotate to assume a predetermined position and orientation along the blood vessel and relative to the target nerve or predetermined non-neural tissue. Once the treatment delivery device 12 is at the desired, predetermined position, the processor 25 may control the generator 14 to deliver denervation therapy to the patient based on one or more treatment parameter values ​​(82). For example, the processor 25 may send a control signal to the generator 14 causing the generator 14 to deliver denervation stimulation. As another example, the processor 25 may notify a clinician, who may then manually control the generator 14 to deliver the denervation stimulation.

[0191] As discussed above, in some examples, processor 25 generates GUI 26 and presents the GUI on a display of user interface 26 of programmer 24. The GUI may present, for example, a graphical representation of an area of ​​a patient, the area of ​​the patient including a target nerve and a corresponding blood vessel (as relevant). The corresponding blood vessel may be, for example, a blood vessel through which the treatment delivery device 12 is introduced to access the target nerve. In some examples, the GUI may include only, for example, a graphical representation of an area of ​​the patient, the area of ​​the patient including a target nerve and a corresponding blood vessel (as relevant). In other examples, the GUI may include other graphical elements, such as a graphical representation of an estimated volume of influence obtained by delivering denervation stimulation to the patient's tissue via the treatment delivery element 12. In some examples, the GUI or another display (e.g., a fluoroscopic examination display) may include a graphical representation of one or more of a series of target locations for delivering treatment determined by processor 25, and may or may not include a graphical representation of the estimated volume of influence. Such a GUI may help clinicians better visualize denervation treatment and better understand the effects of different treatment parameter values ​​(including the location of the treatment delivery element in the patient's body) on the volume of influence.

[0192] In some examples, rather than generating a graphical representation of a volume of influence based on a known treatment program as discussed in some examples above, a user may provide input indicating a desired graphical representation of a volume of influence within a GUI, and the processor 25, in response, may determine treatment parameter values ​​that are expected to result in the volume of influence. The processor 25 may then program the generator 14 with these treatment parameter values, which may be stored as a treatment program.

[0193] Figure 8 It shows that Figure 3 Schematic representation of an example GUI 90 presented on a display of the user interface 26 of the programmer 24 of FIG. By interacting with the GUI 90, a user can generate a graphical representation of an electrical stimulation field, which can be an example of an influence volume. In some examples, a user can be able to create a stimulation field and direct the processor 25 to generate a set of treatment parameter values ​​(e.g., a treatment program) that will best match the stimulation field. In some examples, the user can change the size, shape, or position of the stimulation field within the GUI 90 using a graphical input medium such as a cursor or stylus control. The generated electrical stimulation field can be utilized as a computer model of a treatment field associated with the generated parameters, for example, a volume of influence associated with electrical denervation stimulation. Thus, a clinician can observe the volume of influence using the GUI 90, and the clinician can select or modify one or more of the treatment programs 34 based on the observed volume of influence.

[0194] GUI 90 shows a graphical representation of a therapy delivery device 12 that includes a multi-electrode geometry. Figure 8 In the example of , the therapy delivery device 12 includes four electrodes arranged generally in a ring at different axial positions. Each electrode is coupled to a corresponding electrical conductor within the therapy delivery device 12. Thus, the therapy delivery device 12 includes a plurality of electrical conductors, e.g., wires, cables, etc., extending from the proximal end of the lead to the corresponding electrodes to electrically couple the electrodes to electrical terminals (e.g., electrical terminals of the generator 14).

[0195] Each electrode is individually powered by the generator 14, thereby enabling the delivery of stimulation energy at different axial and angular positions. In some examples, the treatment delivery device 12 may include a combination of complex electrode array geometries and simple electrode array geometries. For example, a ring electrode extending around the entire circumference of the lead may be used in combination with electrodes disposed at different axial and angular positions. Selective activation of the electrodes carried by the treatment delivery device 12 can generate a customized stimulation field that can be directed to a specific side of the treatment delivery device 12 in order to isolate the stimulation field around the target anatomical region.

[0196] GUI 90 shows a side view of therapy delivery device 12, which is shown being guided into blood vessel 98. Figure 8 or Fig. 9 90, but the graphical representation of the therapy delivery device 12 may be spiral and in contact with the inner wall of the graphical representation of the blood vessel 98. The size and shape of the stimulation field 104 generated by the therapy delivery device 12 may be established based on the general physical properties of the tissue and based on the known physical properties of the electrodes of the therapy delivery device 12. In other words, the stimulation field 104 displayed in the GUI 90 may only be a rough estimate of what the stimulation field will look like in the area of ​​the patient including the target nerve. However, in some examples, the physical properties of the actual anatomy of the patient receiving treatment may be used to generate the stimulation field 104. This anatomical information may be presented to the programmer 24 and stored in the memory 28 in the form of patient anatomical data generated by an imaging modality (such as, CT, MRI, or any other mentioned imaging system) Figure 3 ). The processor 25 may generate the stimulation field 104 using, for example, a tissue impedance model, a field propagation model, etc. In some examples, the stimulation field 104 may be a representation of the stimulation field, current density, voltage gradient, or neuronal activation applied to generic human tissue or patient-specific tissue characteristics. In addition, the user may be able to switch between any of these representations when desired.

[0197] The user may use vertical scroll bar 116 or some similar control interface to move stimulation field 104 up or down relative to the longitudinal axis of therapy delivery device 12. As stimulation field 104 moves up or down in response to the user input, programmer 24 automatically selects the appropriate electrode(s) to support vertical movement of stimulation field 104 within GUI 90. GUI 90 includes arrows 119 or similar input media that allow the user to switch between different rotational views.

[0198] In addition, the user can use a horizontal scroll bar 110 or some similar control device to rotate the views shown in the GUI 90, for example, to visualize the stimulation field 104 relative to other tissue sites that are not shown in all views. An arrow 110 can be provided next to the horizontal scroll bar 112 to indicate the orientation of the treatment delivery device 12 relative to the anatomical structure.

[0199] Using a scroll bar 116 or similar input medium to move the stimulation field 104 within the GUI 90 allows the user to evaluate different stimulation field positions without having to manually select electrodes and manually enter parameter values. Alternatively, the processor 25 of the programmer 24 automatically selects electrodes and parameter values ​​in response to the stimulation field 104 being moved by the user. Although the scroll bar 116 is shown as an example of an input medium for moving the stimulation field 104, other types of input media may be used. Examples include up / down arrows or lateral arrows that may be presented on a touch screen or formed by buttons or keys on the programmer 24.

[0200] As a further alternative to manipulating the stimulation field 104, the user can select the stimulation field 104 using a stylus, mouse, or other pointing device and drag the field up, down, or rotationally. In some examples, the mouse or other pointing device can support left-click or right-click functions for performing different operations relative to the stimulation field 104. Using the stylus, a first click on the stimulation field 104 can initiate movement, dragging with the stylus guides movement relative to the schematic diagram of the treatment delivery device 12 in the GUI 90, and a second click can terminate movement. In each case, the processor 25 of the programmer 24 responds to a particular movement by automatically adjusting the electrode combination and stimulation parameters to roughly estimate the characteristics of the stimulation field 104 presented by the GUI 90. As the stimulation parameter values ​​change, the size and shape of the stimulation field 104 presented on the display changes. Similarly, as the electrode combination changes in polarity or electrode selection, the size, shape, or direction of the stimulation field 104 presented on the display changes.

[0201] In some examples, processor 25 of programmer 24 may utilize stimulation templates and select the best fitting stimulation template that is set as the newly modified stimulation field 104 in order to generate therapeutic parameter values ​​for implementing the stimulation field 104. A stimulation template is a predetermined volume-referred stimulation field that processor 25 of programmer 24 may substantially match with the desired stimulation field 104 from the user. Algorithms for generating stimulation parameter values ​​that fit a user-defined stimulation field may be computationally less intensive for processor 25 than algorithms that reference multiple equations or lookup tables to generate stimulation parameters. A stimulation template may be a representation of an electric field or other electrical stimulation-related property (e.g., current density, voltage gradient, or neuronal activation) applied to generic human tissue. For stored stimulation templates, processor 25 may adjust RF energy for changing the size of the stimulation template for covering the desired stimulation field 104 from the user.

[0202] Processor 25 of programmer 24 may limit the rate at which stimulation field 104 moves within GUI 90. In other words, stimulation field 104 may only be moved a certain number of steps per second within GUI 90 (or any other user interface that allows a user to drag a stimulation field). Rate movement limits may prevent unnecessary calculations or ensure that the patient remains comfortable during a real-time programming example.

[0203] In addition to moving the stimulation field 104, the GUI 90 may allow the user to perform one or more operations that result in the reconfiguration of the stimulation field 104. For example, the user may click on the boundary (i.e., the outer diameter) of the stimulation field 104 and drag it inward or outward to resize the stimulation field. Resizing by enlarging or reducing the stimulation field 104 in the GUI 90 may cause the RF energy to increase or decrease, and thus cause the parameter values ​​of the treatment program used to generate the stimulation field 104 to change. In some examples, enlarging or reducing the stimulation field 104 may also cause the selection or deselection of electrodes included in an existing electrode combination. In either case, the processor 25 of the programmer 24 adjusts the electrode combination and / or parameter values ​​in response to the user enlarging or reducing the stimulation field 104.

[0204] When the user clicks on the stimulation field 104 boundary and drags it, the entire stimulation field can be expanded in the same proportion in two dimensions. Alternatively, the stimulation field 104 can be expanded only in the direction in which the user drags the stimulation field. For example, horizontally dragging the field perimeter to enlarge the stimulation field 104 can cause the cross-sectional size of the stimulation field 104 to be enlarged as a whole, thereby keeping the vertical and horizontal aspect ratios constant. Alternatively, horizontal dragging can result in only horizontal expansion, so that the vertical dimension is constant. A constant or variable aspect ratio can be specified by the user as a user preference. Alternatively, the programmer 24 can provide different aspect ratios for expansion and reduction of the stimulation field 104 on a selective basis.

[0205] To zoom in or out on the stimulation field 104, the user may simply click on the stimulation field border within the GUI 90. Alternatively, the user may click on Figure 8 90 , and then click on the border of the stimulation field 104 to drag it inward or outward and thereby adjust the size of the stimulation field. In response, the processor 25 of the programmer 24 can automatically reconfigure (multiple) selected electrodes and / or stimulation parameter values ​​to roughly estimate the resized stimulation field. In this way, the user can generate an influence volume by directly manipulating the stimulation field 104. In each case, the user changes the stimulation field 104 by only changing the representation of the stimulation field 104 presented on the GUI 90, thereby avoiding the need to manually select electrodes and parameter values.

[0206] The user can manipulate the size, shape, and / or position of the stimulation field 104 (or another type of volume of influence in other examples) to, for example, better target the target nerves and / or avoid areas of side effects. Figure 8 1, but the GUI 90 may include a graphical representation of the target nerves, side effect regions, and / or other tissue sites of interest, or may include at least a medical image of the region of the patient superimposed with the graphical representations of the treatment delivery element 12 and the stimulation field 104. In some cases, the target nerves may not be visible in the medical image. In these examples, the graphical representation of the side effect regions and / or other tissue sites of interest may still be useful information to present because it still guides the user to select denervation treatment parameter values ​​that may avoid the side effect regions.

[0207] After selecting a desired stimulation field 104, processor 25 of programmer 24 may determine, for example based on computer model 32, one or more treatment parameter values ​​that are expected to result in the desired stimulation field 104. In some examples, processor 25 may control generator 14 or another medical device to deliver denervation therapy to an area of ​​the patient according to the one or more treatment parameter values.

[0208] Fig. 9 1 is a schematic illustration of another example of a GUI 120 that may be presented on a display of programmer 24. A user may interact with GUI 120 via user interface 26 of programmer 24 to facilitate selecting a desired volume of effect for a denervation therapy. GUI 120 includes a representation of an anatomical region of a patient (e.g., a region including target nerve 102). In GUI 120, a device icon 124 representing a therapy delivery device 12 is displayed within a graphical representation of a blood vessel 100.

[0209] Different shaded portions of the GUI 120 indicate different tissue densities within the region. For example, darker portions may indicate denser tissue. A user may be able to identify different anatomical structures or tissue types by viewing the GUI 120. It should be noted that Fig. 9 The display 120 shown in FIG. 1 is merely an example image, and actual images may include a wider range of shading and a higher image resolution.

[0210] Display 120 further includes pointer 128, "previous" arrow 132, "next" arrow 134, fine control input mechanism 136, and control slider 138. Pointer 128 may be controlled using a mouse and buttons, trackball, touch pad, touch screen, or other mobile input device, which may be part of user interface 26 of programmer 24. A user may use pointer 128 to drag device icons 124 into position or rotate device icons 124. A user may zoom the view to obtain a larger view of an anatomical region, or move up, down, left, or right to view a larger or smaller portion of the region.

[0211] The GUI 120 allows the user to select and adjust the size of the volume of influence 126, and in some examples, the shape of the volume of influence 226, which may be further defined in other orthogonal views. The user may drag the volume of influence 126 using the pointer 128 to define a smaller or larger size, which may correspond to a lower or higher RF energy level. For example, the user may click on the border or perimeter of the volume of influence 126, and then drag the border to expand or contract the volume of influence 126. This adjustment is a coarse control of the size of the volume of influence 126. The user may use the pointer 128 to move the control slider 138 upward to slightly increase the size of the volume of influence 126, or downward to slightly decrease the size of the volume of influence 126.

[0212] Processor 25 of programmer 24 may limit the rate of movement of volume of influence 126. For example, processor 25 may limit the movement of volume of influence 126 within GUI 120 to a certain number of steps per second. This rate movement limit may prevent unnecessary calculations of real-time changes in denervation therapy parameter values ​​that occur as volume of influence 126 is modified.

[0213] The view button 130 may allow the user to switch to another view of the area. Other views may include, for example, a view from another orientation, or a view based on a different imaging technique.

[0214] The following discussion provides further details about the patient's anatomy and physiology as they may be relevant to renal denervation therapy. This section is intended to supplement and expand upon the previous discussion of relevant anatomy and physiology, and is intended to provide additional background information about the disclosed techniques and therapeutic benefits associated with renal denervation. For example, several properties of the renal vasculature may inform the design of therapeutic devices and associated methods for achieving renal neuromodulation via intravascular access, and impose specific design requirements on such devices. Specific requirements may include access to the renal artery, facilitating stable contact between the energy delivery element of the therapeutic delivery device and the luminal surface or wall of the renal artery, and / or effectively modulating the renal nerves using the therapeutic delivery device.

[0215] The sympathetic nervous system (SNS) is a branch of the autonomic nervous system, which is accompanied by the enteric nervous system and the parasympathetic nervous system. It is always active at the basal level (called sympathetic tone) and becomes more active when there is stress. Like other parts of the nervous system, the sympathetic nervous system operates through a series of interconnected neurons. Although many sympathetic neurons are located in the central nervous system (CNS), sympathetic neurons are often considered to be part of the peripheral nervous system (PNS). The sympathetic neurons of the spinal cord (which is part of the CNS) communicate with peripheral sympathetic neurons via a series of sympathetic ganglia. In the ganglion, the spinal cord sympathetic neurons connect peripheral sympathetic neurons by synapses. Therefore, the spinal cord sympathetic neurons are called presynaptic (or preganglionic) neurons, and the peripheral sympathetic neurons are called postsynaptic (or postganglionic) neurons.

[0216] At the synapses within the sympathetic ganglia, preganglionic sympathetic neurons release acetylcholine, a chemical messenger that binds and activates the nicotinic acetylcholine receptors on postganglionic neurons. In response to this stimulus, postganglionic neurons primarily release noradrenaline (norepinephrine). Persistent activation can cause the release of adrenaline from the adrenal medulla. Once released, noradrenaline and adrenaline bind to adrenaline receptors on peripheral tissues. Binding to adrenaline receptors can lead to neural and hormonal responses. Physiological clinical manifestations include one or more of pupil dilation, increased heart rate, occasional vomiting, or increased blood pressure. It can also be seen that increased sweating is caused by the binding of the cholinergic receptors of the sweat glands.

[0217] The sympathetic nervous system is responsible for the multi-stable mechanism in the organism of up-regulation and down-regulation. The fibers from the SNS innervate the tissues in almost every organ system, thereby providing at least some regulatory functions to the characteristics as diverse as pupil diameter, intestinal motility and urine output. This reaction is also referred to as the sympathetic adrenal response of the body, due to the secretion of acetylcholine by the preganglionic sympathetic nerve fibers (and all other sympathetic nerve fibers) that terminate in the adrenal medulla, which activates the secretion of adrenaline (adrenaline / epinephrine) and noradrenaline (noradrenaline / norepinephrine) in a smaller range. Therefore, the reaction that mainly acts on the cardiovascular system is mediated directly via the pulsation transmitted by the sympathetic nervous system and indirectly via the catecholamines secreted from the adrenal medulla.

[0218] Fig.10 is a conceptual and schematic illustration of the sympathetic nervous system (SNS) of a human subject. Fig.10As shown, SNS provides a neural network that allows the brain to communicate with the body. Sympathetic nerves originate in the spine, towards the middle of the spinal cord in the middle lateral cell column (or lateral angle), which begins in the first thoracic segment of the spinal cord and is considered to extend to the second or third lumbar segment. Because its cells begin in the thoracic and lumbar regions of the spinal cord, it can be considered that SNS has thoracolumbar outflow. The axons of these nerves leave the spinal cord by the anterior root / root. They pass near the spinal column (sensory) ganglion, where they enter the anterior ramus of the spinal nerve. However, unlike somatic innervation, they are soon separated by white branch connectors, which are connected to the paravertebral (it is located near the spine) or prevertebral (it is located near the aortic branch) ganglia extending beside the spine.

[0219] In order to reach the target organs and glands, axons should travel long distances in the body, and, to accomplish this, many axons relay their message to a second cell through synaptic transmission. The tip of the axon connects to the dendrites of the second cell across a space (synapse). The first cell (presynaptic cell) sends a neurotransmitter across the synaptic cleft, where it activates the second cell (postsynaptic cell). The message is then carried to the final destination.

[0220] In the SNS and other components of the peripheral nervous system, these synapses are generated at sites called ganglia. The cells that send their fibers are called preganglionic cells, and the cells whose fibers leave the ganglia are called postganglionic cells. As mentioned previously, the preganglionic cells of the SNS are located between the first thoracic (T1) segment and the third lumbar (L3) segment of the spinal cord. Postganglionic cells have their cell bodies in the ganglia and send their axons to target organs or glands.

[0221] The ganglia include not only the sympathetic trunks but also the cervical ganglia (superior, middle, and inferior), which send sympathetic nerve fibers to the organs of the head and chest, and the celiac and mesenteric ganglia, which send sympathetic nerve fibers to the intestines.

[0222] Fig.11 is a conceptual anatomical view of the nerves innervating the left kidney to form the renal plexus surrounding the left renal artery in a human subject. Fig.11 As shown in, the kidney is innervated by the renal plexus RP, which is closely associated with the renal artery. The renal plexus RP is an autonomic plexus surrounding the renal artery and embedded in the adventitia of the renal artery. The renal plexus RP extends along the renal artery until it reaches the substance of the kidney. The fibers that promote the renal plexus RP are produced by the celiac ganglion, superior mesenteric ganglion, aortic renal ganglion and aortic plexus. The renal plexus RP (also known as renal nerves) is mainly composed of sympathetic nerve components. There is no (or at least very little) parasympathetic innervation of the kidney.

[0223] Preganglionic neuron cell bodies are located in the middle lateral cell column of the spinal cord. Preganglionic axons pass through the paravertebral ganglia (they do not have synapses) to become the lesser splanchnic nerve, the smallest splanchnic nerve, the first lumbar splanchnic nerve, the second lumbar splanchnic nerve, and travel to the celiac ganglion, the superior mesenteric ganglion and the aortic renal ganglion. Postganglionic neuron cell bodies exit the celiac ganglion, the superior mesenteric ganglion, and the aortic renal ganglion to the renal plexus RP and are distributed to the renal vascular system.

[0224] Messages travel through SNS in a two-way flow. Outgoing messages can trigger changes in different parts of the body simultaneously. For example, the sympathetic nervous system can increase heart rate; dilate bronchial passages; reduce motility (movement) of the large intestine; constrict blood vessels; increase esophageal motility; cause pupil dilation, piloerection (goose bumps), and perspiration (sweating); and raise blood pressure. Incoming messages carry information from various organs and sensory receptors in the body to other organs, especially the brain.

[0225] Hypertension, heart failure, and chronic kidney disease are some of the many disease states that can be caused by chronic activation of the SNS (particularly the renal sympathetic nervous system). Chronic activation of the SNS is a maladaptive response that drives the progression of these disease states. Drug management of the renin-angiotensin-aldosterone system (RAAS) has been a long-standing method for reducing the overactivity of the SNS, but is somewhat inefficient.

[0226] As mentioned above, the renal sympathetic nervous system has been identified experimentally and in humans as a major contributor to the complex pathophysiology of hypertension, states of volume overload (such as heart failure), and progressive renal disease. Studies using radiotracer dilution methods to measure norepinephrine efflux from the kidneys to plasma have shown that the increased renal norepinephrine (NE) overflow rate in patients with essential hypertension (especially in young hypertensive patients) (which is consistent with the increased NE overflow from the heart) is consistent with the hemodynamic profile commonly seen in early hypertension and is characterized by increased heart rate, cardiac output, and renal vascular resistance. It is now known that essential hypertension is usually neurogenic, often accompanied by significant sympathetic nervous system overactivity.

[0227] Activation of cardiorenal sympathetic nerve activity may be even more pronounced in heart failure, as evidenced by an exaggerated increase in NE spillover from the heart and kidneys to plasma in this patient population. Consistent with this concept is the recent demonstration of a strong negative predictive value of renal sympathetic nerve activation for all-cause mortality and cardiac transplantation in patients with congestive heart failure, independent of overall sympathetic nerve activity, glomerular filtration rate, and left ventricular ejection fraction. These findings support the concept that treatment regimens designed to reduce renal sympathetic nerve stimulation have the potential to improve survival in patients with heart failure.

[0228] Chronic and end-stage renal disease are characterized by elevated sympathetic activation. In patients with end-stage renal disease, plasma levels of norepinephrine above the median have been shown to be a precursor to both all-cause mortality and death caused by cardiovascular disease. This is also true for patients with diabetes or contrast-induced nephropathy. There is convincing evidence that sensory afferent signals originating from the diseased kidneys are the main cause of initiation and maintenance of elevated central sympathetic outflow in this patient population; this promotes the well-known adverse consequences of chronic sympathetic overactivity, such as hypertension, left ventricular hypertrophy, ventricular arrhythmias, sudden cardiac death, insulin resistance, diabetes, and metabolic syndrome.

[0229] Sympathetic nerves to the kidneys terminate in blood vessels, juxtaglomerular apparatus, and renal tubules. Stimulation of renal sympathetic nerves results in increased renin release, increased sodium (Na + ) reabsorption, and the reduction of renal blood flow. These components of the neural regulation of renal function are greatly stimulated in the disease state characterized by elevated sympathetic tone and clearly promote the increase in blood pressure in hypertensive patients. The reduction of renal blood flow and glomerular filtration rate caused by renal sympathetic nerve efferent stimulation may be the basis of the loss of renal function in cardiorenal syndrome (which is renal insufficiency as a progressive complication of chronic heart failure), with a clinical course that fluctuates with the clinical state and treatment of the patient usually. The pharmacological strategy for hindering the results of renal efferent sympathetic nerve stimulation includes centrally acting sympathetic drugs, beta blockers (intended to reduce renin release), angiotensin converting enzyme inhibitors and receptor blockers (intended to prevent the effect of angiotensin II caused by renin release and aldosterone activation) and diuretics (intended to counteract sodium and water retention mediated by renal sympathetic nerves). However, current pharmacological strategies have significant limitations, including limited efficacy, compliance issues, side effects and others.

[0230] The kidneys communicate with the entire structure of the central nervous system via renal sensory afferent nerves. Several forms of "renal injury" can cause activation of sensory afferent signals. For example, renal ischemia, a decrease in stroke volume or renal blood flow, or a large amount of adenosine can trigger activation of afferent nerve communication.

[0231] Fig. 12A and Fig. 12B Conceptual anatomical views of the human body depicting the efferent and afferent neural communications between the brain and kidneys, respectively. Fig. 12A and Fig. 12BAs shown in , this afferent communication can be from the kidneys to the brain or from one kidney to another kidney (via the central nervous system). These afferent signals are all centrally integrated and can result in increased sympathetic outflow. The sympathetic impulses are directed toward the kidneys, thereby activating the RAAS and inducing increased renin secretion, sodium retention, volume retention, and vasoconstriction. Central sympathetic overactivity also affects other organs and body structures innervated by the sympathetic nerves, such as the heart and peripheral vasculature, resulting in the described adverse effects of sympathetic activation, some aspects of which also contribute to increased blood pressure.

[0232] Thus, physiology indicates that (i) modulation of tissues with efferent sympathetic nerves may reduce inappropriate renin release, sodium retention, and decrease renal blood flow, and (ii) modulation of tissues with afferent sensory nerves may reduce systemic contributions to hypertension and other disease states associated with increased central sympathetic tone through its direct effects on the posterior hypothalamus and contralateral kidney. In addition to the central hypotensive effects of denervation of the afferent kidney, an expected reduction in central sympathetic outflow to various other sympathetically innervated organs, such as the heart and vasculature, is contemplated.

[0233] As provided above, renal denervation may be valuable in the treatment of several clinical conditions characterized by increased global and specific renal sympathetic nerve activity, such as hypertension, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic end-stage renal disease, inappropriate fluid retention in heart failure, cardiorenal syndrome, and sudden death. Since the reduction in afferent nerve signals contributes to a systemic reduction in sympathetic tone / impulsivity, renal denervation may also be useful in the treatment of other conditions associated with systemic sympathetic hyperactivity. Thus, renal denervation may also benefit other organs and body structures innervated by sympathetic nerves, including in Fig.10 Those identified in. For example, as previously discussed, reduction of central sympathetic nerve impulses may reduce insulin resistance that afflicts people with metabolic syndrome and type II diabetes. In addition, patients with osteoporosis are also sympathetically activated and may also benefit from downregulation of sympathetic nerve impulses that accompanies renal denervation.

[0234] According to the present technology, neuromodulation (eg, denervation) of the left and / or right renal plexus RP, which is closely associated with the left and / or right renal arteries, may be achieved via intravascular access.

[0235] Fig.13A and Fig. 13B are conceptual anatomical views of the arterial and venous vasculature of a human subject, respectively. Fig.13AAs shown in , the aorta carries blood moved by the contraction of the heart from the left ventricle of the heart. The aorta descends through the chest and branches into the left and right renal arteries. Below the renal arteries, the aorta branches at the left and right common iliac arteries. The left and right common iliac arteries descend through the left and right legs, respectively, and connect to the left and right femoral arteries.

[0236] like Fig. 13B As shown in , blood collects in the veins and enters the iliac veins through the femoral veins and into the inferior vena cava, returning to the heart. The inferior vena cava branches into the left and right renal veins. Above the renal veins, the inferior vena cava ascends to deliver blood to the right atrium of the heart. From the right atrium, blood is pumped through the right ventricle into the lungs, where the blood is oxygenated. From the lungs, oxygenated blood is delivered to the left atrium. From the left atrium, oxygenated blood is delivered through the left ventricle back to the aorta.

[0237] The femoral artery can be accessed and cannulated only at the base of the femoral triangle below the midpoint of the inguinal ligament. A catheter can be percutaneously inserted into the femoral artery through this access site, passed through the iliac arteries and aorta, and placed in the left or right renal artery. This includes an intravascular route that provides minimally invasive access to the respective renal artery and / or other renal blood vessels.

[0238] The wrist, upper arm, and shoulder areas can provide other locations for introducing a catheter into the arterial system. For example, catheterization of the radial artery, brachial artery, or axillary artery can be used in selected cases. A catheter introduced via these entry points can be passed through the subclavian artery on the left side (or via the subclavian and brachiocephalic arteries on the right side), through the aortic arch, down along the descending aorta, and into the renal arteries using standard angiographic techniques.

[0239] Since neuromodulation of the left and / or right renal plexus RP can be achieved through intravascular access according to the present technology, the properties and characteristics of the renal vasculature can impose constraints on and / or inform the design of devices, systems and methods for achieving such renal neuromodulation. Some of these properties and characteristics may vary across patient populations and / or vary over time within a particular patient, as well as in response to disease states such as hypertension, chronic kidney disease, vascular disease, end-stage renal disease, insulin resistance, diabetes, metabolic syndrome, etc. As explained herein, these properties and characteristics may be related to the efficacy of the procedure and the specific design of the intravascular device. Properties of interest may include, for example, material / mechanical properties, spatial properties, fluid dynamic / hemodynamic properties, and / or thermodynamic properties.

[0240] As discussed above, a catheter or another treatment delivery device can be percutaneously advanced into the left or right renal artery via a minimally invasive intravascular path. However, minimally invasive renal artery access may be challenging, for example, because compared to some other arteries that are routinely accessed using a catheter, the renal artery is often extremely tortuous, can be a relatively small diameter, and / or can be a relatively short length. In addition, renal artery atherosclerosis is common in many patients, particularly those with cardiovascular disease. Renal artery anatomy can also be significantly different from patient to patient, which further complicates minimally invasive access. For example, significant patient-to-patient variation can be seen in relative tortuosity, diameter, length, and / or atherosclerotic plaque load and the take-off angle of the renal artery from the aortic branch. These and other aspects of renal artery anatomy and its variation across patient populations can be considered for devices, systems, and methods for realizing renal neuromodulation via intravascular access when minimally invasive access to the renal artery.

[0241] In addition to complicating access to the renal artery, the details of renal anatomy can also complicate establishing stable contact between the lumen surface or wall of the treatment delivery device and the renal artery. When the treatment delivery device includes an energy delivery element (such as, an electrode), consistent positioning and appropriate contact forces applied to the vessel wall by the energy delivery element may be desirable for achieving predictable denervation treatment delivery. However, the narrow space in the renal artery and the tortuosity of the artery may hinder navigation. In addition, establishing consistent contact may be complicated by patient movement, breathing and / or the cardiac cycle, because these factors may cause significant movement of the renal artery relative to the aorta, and the cardiac cycle may instantaneously expand the renal artery (i.e., cause the wall of the artery to pulsate).

[0242] Even after entering the renal artery and facilitating stable contact between the treatment delivery device and the luminal surface of the artery, the nerves in and around the adventitia of the artery can still be safely regulated via the treatment delivery device. Given the potential clinical complications associated with thermal treatment, it can be non-trivial to effectively apply thermal treatment to the renal artery. For example, the intima and media of the renal artery are relatively vulnerable to thermal damage. As discussed in more detail below, the intima-media thickness separating the lumen from its adventitia indicates that the target renal nerve can be several millimeters away from the luminal surface of the artery. Sufficient energy can be delivered to the target renal nerve or heat can be removed from the target renal nerve to regulate the target renal nerve without excessively cooling or heating the wall to the extent of freezing, drying, or otherwise being potentially affected to an undesirable extent. A potential clinical complication associated with overheating is thrombosis caused by coagulation of blood flowing through the artery. Assuming that such thrombus may cause renal infarction, thereby causing irreversible damage to the kidney, thermal treatment can be applied cautiously in the renal artery. Therefore, when applying energy (e.g., heating thermal energy) and / or removing heat from tissue within the renal artery (e.g., cooling thermal conditions), the complex fluid dynamics and thermodynamic conditions that exist in the renal artery during treatment (particularly those conditions that may affect the heat transfer dynamics at the treatment site) can be considered.

[0243] Since the location of treatment may also affect clinical efficacy, the treatment delivery device may also be configured to allow the energy delivery element to be adjustably positioned and repositioned in the renal artery. For example, assuming that the renal nerves can be spaced circumferentially around the renal artery, it may be attractive to apply full-circle treatment in the renal artery. In some cases, full-circle damage that may be caused by continuous circumferential treatment may potentially be related to renal artery stenosis. Therefore, it may be desirable to form more complex damage along the longitudinal dimension of the renal artery via the mesh structure described herein and / or repositioning the treatment delivery device to multiple treatment positions, and the computer modeling technology described above may be assisted. However, it should be noted that the benefits of creating circumferential ablation may outweigh the risks of renal artery stenosis, or certain embodiments may be used or the risk may be mitigated in certain patients, and creating circumferential ablation may be the goal. In addition, variable positioning and repositioning of the treatment delivery device may prove to be useful in cases where the renal artery is particularly tortuous or there is a proximal branch vessel that is detached from the main vessel of the renal artery, resulting in treatment in certain positions being challenging. The manipulation of the device in the renal artery may also consider the potential adverse mechanical interaction between the device and the renal artery. Movement of the device within the artery, for example by insertion, manipulation, unblocking bends, etc., can result in dissection, perforation, intimal denudation, or disruption of the internal elastic lamina.

[0244] Blood flow through the renal artery may be temporarily blocked for a short period of time with little or no complications. However, blockage for a significant period of time may be avoided because damage to the kidney, such as ischemia, is to be prevented. It may be beneficial to avoid blockage altogether, or to limit the duration of blockage, for example, to 2-5 minutes when blockage is beneficial.

[0245] Based on the challenges described above of: (1) renal artery access; (2) maintaining consistent and stable placement of therapeutic elements against the vessel wall; (3) effective delivery of therapy across the vessel wall; (4) positioning and potentially repositioning the therapeutic device to allow for multiple treatment locations; and (5) avoiding or limiting the duration of blood flow obstruction, various independent and dependent attributes of the renal vasculature that may be of interest include, for example, (a) vessel diameter, vessel length, intima-media thickness, and (a) the properties of the renal artery and / or the aorta. The properties of the renal artery include: (i) the thickness, friction coefficient, and tortuosity of the aorta; (b) the expansibility, stiffness, and elastic modulus of the vessel wall; (c) the peak systolic and end-diastolic blood flow velocities, as well as the average systolic-diastolic peak blood flow velocities, and the average / maximum volumetric blood flow rate; (d) the specific heat capacity of the blood and / or the vessel wall, the thermal conductivity of the blood and / or the vessel wall, and / or the thermal convection and / or radiative heat transfer of the blood flowing through the vessel wall treatment site; (e) the movement of the renal artery relative to the aorta caused by breathing, patient movement, and / or blood flow pulsation; and (f) the exit angle of the renal artery relative to the aorta. These properties will be discussed in more detail in conjunction with the renal artery. However, depending on the device, system, and method used to achieve renal neuromodulation, such properties of the renal artery may also guide and / or constrain design characteristics.

[0246] As mentioned above, the device positioned in the renal artery can conform to the geometry of the artery. The renal artery tube diameter DRA can be in the range of about 2-10mm, wherein the DRA of most patient populations is about 4mm to about 8mm, and an average of about 6mm. The renal artery tube length LRA between the renal artery orifice at the aorta / renal artery junction and the distal branch of the renal artery can be in the range of about 5-70mm, and a large part of the patient population can be in the range of about 20-50mm. Because the target renal plexus is embedded in the adventitia of the renal artery, the composite intima-media thickness IMT (i.e., the radially outward distance from the surface of the arterial cavity to the adventitia containing the target neural structure) is also noteworthy, and for some patients can be in the range of about 0.5-2.5mm, wherein an average of about 1.5mm. Although a certain treatment depth can reach the target nerve fiber, the treatment can not be too deep (e.g., greater than 5mm from the inner wall of the renal artery) to avoid non-target tissues and anatomical structures, such as the renal vein.

[0247] An additional property of the renal artery that may be of interest is the degree of renal motion relative to the aorta caused by respiration and / or blood flow pulsatility. The patient's kidney at the distal end of the renal artery may move up to 4 inches (approximately 10 cm) cranially with respiratory excursion. This may cause significant movement of the renal artery connecting the aorta and the kidney, thereby requiring a unique balance of rigidity and flexibility from the treatment delivery device to maintain contact between the thermal or electrical treatment element and the tube wall during the respiratory cycle. In addition, the emission angle between the renal artery and the aorta may vary significantly between patients, and may also vary dynamically within a patient, for example due to renal motion. The emission angle can typically be in the range of about 30°-135°.

[0248] The techniques described in this disclosure may be implemented, at least in part, in hardware, software, firmware, or any combination thereof. For example, various aspects of the described techniques may be implemented in a processing circuit system (including one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or any other equivalent integrated or discrete logic circuit systems) and any combination of such components. The term "processor" or "processing circuit system" may generally refer to any of the aforementioned logic circuit systems, either alone or in combination with other logic circuit systems or any other equivalent circuit systems. A control unit including hardware may also perform one or more of the techniques of this disclosure.

[0249] Such hardware, software, and firmware may be implemented in the same device or in multiple separate devices to support the various technologies described in this disclosure. In addition, any of the described instructions, units, modules, or components may be implemented together, or may be implemented separately as discrete but interoperable logic devices. Depicting different features as modules or units is intended to highlight different functional aspects and does not necessarily imply that such modules or units must be implemented by separate hardware, firmware, or software components. Instead, the functionality associated with one or more modules or units may be performed by separate hardware, firmware, or software components or integrated in common or separate hardware, firmware, or software components.

[0250] The techniques described in the present disclosure may also be implemented or encoded into a computer system readable medium, such as a computer system readable storage medium containing instructions. Instructions embedded or encoded into a computer system readable medium (including a computer system readable storage medium) may be such as when the instructions included or encoded into the computer system readable storage medium are executed by a processing circuit system so that one or more programmable processors or other processors implement one or more of the techniques described herein. Computer system readable storage media may include random access memory (RAM), read-only memory (ROM), programmable read-only memory (PROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), flash memory, hard disk, compact disk ROM (CD-ROM), floppy disk, cassette, magnetic medium, optical medium or other computer system readable medium. In some examples, the product may include one or more computer system readable storage media, for example, non-transient computer system readable storage media.

[0251] Various examples have been described. These and other examples are within the scope of the following claims.

Claims

1. A method comprising: A plurality of treatment programs are determined by a processor, the plurality of treatment programs comprising: a first treatment program having a first set of treatment parameter values; a second treatment program having a second set of treatment parameter values; determining, by the processor, one or more tissue properties of tissue proximate to a target nerve and blood vessel of the patient; After determining the plurality of treatment programs, determining, by the processor, a first estimated volume of impact of a denervation treatment delivered by a treatment delivery device disposed within the blood vessel according to the first treatment program based on the one or more tissue characteristics; After determining the plurality of treatment programs, determining, by the processor, a second estimated volume of influence of the denervation therapy delivered by the treatment delivery device according to the second treatment program based on the one or more tissue characteristics; and The first treatment procedure or the second treatment procedure is selected, by the processor, based on the first estimated influence volume and the second influence volume.

2. The method according to claim 1, further comprising: A therapy delivery device is controlled by the processor to deliver denervation therapy to the target nerve based on the selected first or second therapy program.

3. The method according to claim 1, further comprising: receiving user input indicating a target volume of influence; as well as The first set of treatment parameter values ​​for the first treatment procedure is determined or generated based on the target influence volume.

4. The method according to claim 1, further comprising: determining, by the processor, a treatment location for delivering denervation therapy; as well as The denervation therapy is delivered to the treatment location using a therapy delivery device according to the selected first or second therapy procedure.

5. The method according to claim 1, further comprising: determining, by the processor, a treatment location for delivering denervation therapy; as well as A recommended treatment plan is displayed using a user interface based on the treatment location and the selected first or second treatment procedure for denervation therapy delivery.

6. The method according to claim 1, wherein: The one or more tissue properties include one or more of electrical impedance, thermal conductivity, acoustic impedance, chemical diffusivity, optical transmittance, or tissue density.

7. The method according to claim 1, wherein: The selected first or second treatment procedure results in damage to the target nerve and avoids damage to a predetermined side effect area.

8. The method according to claim 1, wherein: The first set of treatment parameter values ​​indicates at least one of an electrical signal parameter, a thermal signal parameter, an ultrasound signal parameter, a microwave signal parameter, an optical parameter, or a chemical dosage parameter.

9. A system comprising: a memory configured to store one or more tissue characteristics of tissue proximate to a target nerve and blood vessel of a patient; as well as a processor coupled to the memory and configured to: determining a plurality of treatment programs, the plurality of treatment programs comprising a first treatment program and a second treatment program; After determining the plurality of treatment procedures, determining a first estimated volume of impact of a denervation treatment delivered by a treatment delivery device disposed within the blood vessel according to the first treatment procedure based on the one or more tissue characteristics; after determining the plurality of treatment programs, determining a second estimated volume of impact of a denervation therapy delivered by the treatment delivery device disposed within the blood vessel according to the second treatment program based on the one or more tissue characteristics; selecting the first treatment procedure or the second treatment procedure based on the first estimated influence volume and the second estimated influence volume; as well as The therapy delivery device is controlled to deliver the denervation therapy to the patient based on the selected first or second therapy program.

10. The system according to claim 9, wherein: The processor is configured to: The therapy delivery device is moved to a predetermined position within the blood vessel based on the selected first or second therapy procedure.

11. The system according to claim 9, wherein: The processor is configured to: determining a treatment location for delivering denervation therapy; and The denervation therapy is delivered to the treatment location using a therapy delivery device based on the selected first or second therapy procedure.

12. The system of claim 9, further comprising: Display, used to present treatment plans, Wherein, the processor is configured to: determining a treatment location for delivering denervation therapy; and A recommended treatment plan is presented on the display.

13. The system according to claim 9, wherein: The one or more tissue properties include one or more of electrical impedance, thermal conductivity, acoustic impedance, chemical diffusivity, optical transmittance, or tissue density.

14. The system according to claim 9, wherein: The delivered denervation therapy using the selected first or second treatment program results in damage to the target nerve and avoids damage to the predetermined side effect area.

15. The system according to claim 9, wherein: The first treatment program includes a set of treatment parameter values, the set of parameter values ​​including at least one of electrical signal parameters, thermal signal parameters, ultrasound signal parameters, microwave signal parameters, optical parameters or chemical dosage parameters.

16. A method comprising: determining, by a processor, a plurality of treatment programs; determining, by the processor, one or more tissue properties of tissue proximate to a target nerve and blood vessel of the patient; after determining the plurality of treatment programs, determining, by the processor, for each of the treatment programs in the plurality of treatment programs, an estimated volume of impact of the denervation therapy delivered by the treatment delivery device according to the corresponding treatment program based on the one or more tissue characteristics; selecting, by the processor, at least one treatment procedure from among the plurality of treatment procedures based on the estimated impact volume; as well as A therapy delivery device is controlled by the processor to deliver denervation therapy to the target nerve based on the selected at least one therapy program.

17. The method of claim 16, wherein: Each of the plurality of treatment programs has a corresponding set of treatment parameter values, the treatment parameter values ​​comprising at least one of electrical signal parameters, thermal signal parameters, ultrasound signal parameters, microwave signal parameters, optical parameters, or chemical dosage parameters.

18. The method of claim 16, wherein: The one or more tissue properties include one or more of electrical impedance, thermal conductivity, acoustic impedance, chemical diffusivity, optical transmittance, or tissue density.

19. The method of claim 16, wherein: The denervation therapy delivered using the selected treatment program results in damage to the target nerve and avoids damage to the predetermined side effect area.

20. The method of claim 16, wherein: receiving user input indicating a target volume of influence; and A set of treatment parameter values ​​for a treatment procedure in the plurality of treatment procedures is determined or generated based on the target influence volume.

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