Methods and Apparatus for Pulsed Electric Field Neuromodulation Via an Intra-to-Extravascular Approach

Abstract

Methods and apparatus are provided for pulsed electric field neuromodulation via an intra-to-extravascular approach, e.g., to effectuate irreversible electroporation or electrofusion, necrosis and/or inducement of apoptosis, alteration of gene expression, changes in cytokine upregulation and other conditions in target neural fibers. In some embodiments, the ITEV PEF system comprises an intravascular catheter having one or more electrodes configured for intra-to-extravascular placement across a wall of patient's vessel into proximity with target neural fibers. With the electrode(s) passing from an intravascular position to an extravascular position prior to delivery of the PEF, a magnitude of applied voltage or energy delivered via the electrode(s) and necessary to achieve desired neuromodulation may be reduced relative to an intravascular PEF system having one or more electrodes positioned solely intravascularly. The methods and apparatus of the present invention may, for example, be used to modulate one or more target neural fibers that contribute to renal function.

I/We claim: 
     
         1 . Apparatus for pulsed electric field neuromodulation via an intra-to-extravascular approach, the apparatus comprising:
 a pulsed electric field generator; and   at least one electrode electrically coupled to the pulsed electric field generator, the electrode configured for intravascular delivery and extravascular placement via an intra-to-extravascular approach,   wherein the electrode is configured for extravascular delivery of a pulsed electric field to induce neuromodulation.   
     
     
         2 . The apparatus of  claim 1 , wherein the electrode comprises at least one bipolar electrode pair having a first electrode and a second electrode, the bipolar electrode pair coupled to the pulsed electric field generator. 
     
     
         3 . The apparatus of  claim 2 , wherein the apparatus is configured for extravascular delivery of the pulsed electric field across the bipolar electrode pair. 
     
     
         4 . The apparatus of  claim 2 , wherein the first electrode is configured for extravascular placement via an intra-to-extravascular approach, and the second electrode is configured for intravascular placement. 
     
     
         5 . The apparatus of  claim 4 , wherein the first electrode comprises an active electrode and the second electrode comprises a return electrode. 
     
     
         6 . The apparatus of  claim 2 , wherein both the first electrode and the second electrode are configured for extravascular placement via an intra-to-extravascular approach. 
     
     
         7 . The apparatus of  claim 2 , wherein the first electrode and the second electrode are longitudinally spaced apart from one another in a deployed configuration. 
     
     
         8 . The apparatus of  claim 2 , wherein the first electrode and the second electrode are angularly-aligned with one another relative to a circumference of a patient's vasculature. 
     
     
         9 . The apparatus of  claim 1  further comprising an external ground pad, wherein the electrode is configured for monopolar extravascular delivery of the pulsed electric field to induce neuromodulation. 
     
     
         10 . The apparatus of  claim 1  further comprising a piercing element configured for intravascular delivery, the piercing element configured to pierce a wall of vasculature of a patient from within the vasculature. 
     
     
         11 . The apparatus of  claim 10 , wherein the electrode is configured for extravascular placement through a wall piercing created with the piercing element. 
     
     
         12 . The apparatus of  claim 10 , wherein the electrode comprises the piercing element. 
     
     
         13 . The apparatus of  claim 10 , wherein the piercing element comprises a needle or cannula. 
     
     
         14 . The apparatus of  claim 13 , wherein the electrode is configured for extravascular placement through a lumen of the needle. 
     
     
         15 . The apparatus of  claim 1 , wherein the electrode is coupled to a catheter. 
     
     
         16 . The apparatus of  claim 15 , wherein the electrode is coupled to an expandable element of the catheter. 
     
     
         17 . The apparatus of  claim 1 , wherein the electrode is configured for delivery via a catheter. 
     
     
         18 . The apparatus of  claim 1 , wherein the apparatus is configured for extravascular infusion of agents. 
     
     
         19 . The apparatus of  claim 18 , wherein the apparatus is configured for extravascular infusion of agents that enhance neuromodulation or provide protective effects. 
     
     
         20 . A method for pulsed electric field neuromodulation via an intra-to-extravascular approach, the method comprising:
 intravascularly advancing at least one electrode to a treatment site within vasculature of a patient;   passing a portion of the electrode through at least a portion of a wall of the vasculature to position the electrode at an extravascular location via an intra-to-extravascular approach; and   extravascularly delivering a pulsed electric field via the electrode to induce neuromodulation.   
     
     
         21 . The method of  claim 20 , wherein intravascularly advancing at least one electrode to a treatment site within vasculature of a patient further comprises intravascularly moving the electrode to a treatment site within a renal artery of the patient. 
     
     
         22 . The method of  claim 20 , wherein intravascularly advancing at least one electrode to a treatment site within vasculature of a patient further comprises intravascularly moving an intravascular catheter having the electrode to the treatment site within the vasculature of the patient. 
     
     
         23 . The method of  claim 22 , wherein passing a portion of the electrode through at least a portion of a wall of the vasculature to positioning the electrode at an extravascular location via an intra-to-extravascular approach further comprises expanding an expandable element of the catheter. 
     
     
         24 . The method of  claim 20 , wherein intravascularly advancing at least one electrode to a treatment site within vasculature of a patient further comprises moving the electrode through an intravascular catheter positioned at the treatment site. 
     
     
         25 . The method of  claim 20 , wherein extravascularly delivering a pulsed electric field to induce neuromodulation further comprises extravascularly applying the pulsed electric field to modulate a neural fiber that contributes to renal function. 
     
     
         26 . The method of  claim 25 , wherein modulating a neural fiber that contributes to renal function further comprises inducing an effect in the neural fiber chosen from the group consisting of irreversible electroporation, electrofusion, necrosis, apoptosis, gene expression alteration, cytokine upregulation alteration, and combinations thereof. 
     
     
         27 . The method of  claim 20  wherein passing a portion of the electrode through at least a portion of a wall of the vasculature to positioning the electrode at an extravascular location via an intra-to-extravascular approach further comprises piercing the wall of the vasculature, and advancing the electrode through the wall piercing. 
     
     
         28 . The method of  claim 27 , wherein piercing the wall of the vasculature further comprises forcing the electrode through the wall of the vasculature. 
     
     
         29 . The method of  claim 20 , wherein advancing at least one electrode to a treatment site further comprises advancing at least one bipolar electrode pair to the treatment site. 
     
     
         30 . The method of  claim 29 , wherein passing a portion of the electrode through at least a portion of a wall of the vasculature to positioning the electrode at an extravascular location via an intra-to-extravascular approach further comprises moving the bipolar electrode pair extravascularly, and wherein extravascularly delivering a pulsed electric field further comprises extravascularly delivering the pulsed electric field across the bipolar electrode pair. 
     
     
         31 . The method of  claim 29 , wherein passing a portion of the electrode through at least a portion of a wall of the vasculature to positioning the electrode at an extravascular location via an intra-to-extravascular approach further comprises positioning a first electrode of the bipolar electrode pair at the extravascular location and positioning a second electrode of the bipolar electrode pair at an intravascular location. 
     
     
         32 . The method of  claim 20  further comprising infusing an agent to enhance the neuromodulation. 
     
     
         33 . The method of  claim 20  further comprising infusing an agent to protect non-target tissue. 
     
     
         34 . A method for pulsed electric field neuromodulation via an intra-to-extravascular approach, the method comprising:
 intravascularly advancing a catheter to a treatment site within vasculature of a patient;   positioning at least one electrode at an extravascular location via the catheter utilizing an intra-to-extravascular approach; and   extravascularly delivering a pulsed electric field via the electrode to induce neuromodulation.   
     
     
         35 . The method of  claim 34  wherein delivering the pulse electric field induces irreversible electroporation in neural fibers related to renal function. 
     
     
         36 . An apparatus for pulsed electric field neuromodulation, comprising:
 a pulsed field generator;   an elongated element configured to be moved within a vascular structure of a patient;   at least one electrode having an intravascular portion associated with the elongated element and an extravascular portion configured to be passed through a wall of the vascular structure, wherein the electrode is electrically coupled to the pulsed field generator; and   an actuator associated with the electrode, wherein the actuator is configured to move the electrode from a first position in which the extravascular portion of the electrode is within the vascular structure and a second position in which the extravascular portion of the electrode is located at an extravascular location for extravascular delivery of a pulsed electric field.   
     
     
         37 . The apparatus of  claim 36 , wherein the electrode comprises at least one bipolar electrode pair having a first electrode and a second electrode, the bipolar electrode pair coupled to the pulsed field generator. 
     
     
         38 . The apparatus of  claim 37 , wherein the extravascular portion of the electrode comprises the bipolar electrode pair. 
     
     
         39 . The apparatus of  claim 37 , wherein the intravascular portion of the electrode comprises the first electrode of the bipolar electrode pair and the extravascular portion of the electrode comprises the second electrode of the bipolar electrode pair. 
     
     
         40 . The apparatus of  claim 37 , wherein the first electrode and the second electrode are longitudinally spaced apart from one another in the second position. 
     
     
         41 . The apparatus of  claim 36  further comprising an external ground pad, wherein the extravascular portion of the electrode is configured for monopolar extravascular delivery of the pulsed electric field. 
     
     
         42 . The apparatus of  claim 36 , wherein the actuator comprises a piercing element configured to pierce a wall of the vascular structure during movement of the extravascular portion of the electrode from the first position to the second position. 
     
     
         43 . The apparatus of  claim 36 , wherein the extravascular portion of the electrode comprises a piercing element configured to pierce a wall of the vascular structure during movement of the extravascular portion of the electrode from the first position to the second position. 
     
     
         44 . The apparatus of  claim 36  further comprising infusate, wherein the apparatus is configured for extravascular infusion of the infusate. 
     
     
         45 . The apparatus of  claim 44 , wherein the infusate comprises neuromodulation-enhancing infusate or protective infusate. 
     
     
         46 . The apparatus of  claim 36 , wherein the actuator comprises an inflatable balloon. 
     
     
         47 . The apparatus of  claim 36 , wherein the actuator comprises an expandable cage or basket. 
     
     
         48 . The apparatus of  claim 36 , wherein the actuator comprises a transition element having a profile configured to direct the extravascular portion of the electrode radially outward as the extravascular portion of the electrode is moved from the first position to the second position. 
     
     
         49 . An apparatus for pulsed electric field neuromodulation, comprising:
 a pulsed field generator;   a bipolar electrode pair having first and second electrodes, the bipolar electrode pair electrically coupled to the pulsed field generator; and   a catheter having an actuator,   wherein the catheter is configured to position the bipolar electrode pair within a vascular structure of a patient, and   wherein the actuator is configured to temporarily move non-insulated portions of the bipolar electrode pair from positions within the vascular structure to extravascular positions for extravascular delivery of a bipolar pulsed electric field.