Applications of the present invention relate generally to electrical manipulation of nerve tissue. Some applications of the present invention relate more specifically to apparatus and techniques for facilitating location, excitation, and/or ablation of nerve tissue.
Hypertension is a prevalent condition in the general population, particularly in older individuals. Sympathetic nervous pathways, such as those involving the renal nerve, are known to play a role in regulating blood pressure. Ablation of renal nerve tissue from the renal artery is a known technique for treating hypertension.
Apparatus is provided in which an effector unit has an ultrasound transducer and electrodes. The effector unit is advanced into a blood vessel of a subject. The effector unit has an expanded state in which it presses the electrodes into the vessel wall of the blood vessel, thereby holding the ultrasound transducer in a position and orientation suitable for the application of ablative ultrasound to the vessel wall. A non-ablative current (e.g., an excitatory current or a blocking current) is applied to the vessel wall in order to facilitate location of nerve tissue within the vessel wall, and/or monitoring of the progress of ablation of the nerve tissue.
There is therefore provided, in accordance with an application of the present invention, apparatus for use with a blood vessel of a subject, the blood vessel having a vessel wall, and the apparatus including:
In an application, the effector unit includes an expandable basket, the electrodes are disposed on the expandable basket, and the transducer is disposed inside the expandable basket.
In an application, the effector unit includes a balloon, the electrodes are disposed on the balloon, and the transducer is disposed inside the balloon.
In an application, in the expanded state the electrodes are arranged in a ring around the central longitudinal axis of the effector unit, and the transducer is oriented to direct the ultrasound radially outwardly through the ring.
In an application, the transducer is disposed on the central longitudinal axis of the effector unit.
In an application, the electrodes are distributed circumferentially around the transducer in at least the expanded state of the effector unit.
In an application, the control circuitry is configured to drive the electrodes to apply an excitatory current to the vessel wall.
In an application, the control circuitry is configured to drive the electrodes to apply an ablative current to the vessel wall.
In an application, the apparatus further includes a pressure sensor operable by the control circuitry, and the control circuitry is configured:
In an application, the control circuitry is configured to, in response to the received data and while the effector unit is in the expanded state, operate the transducer to transmit ultrasound.
In an application, in the expanded state of the effector unit:
There is further provided, in accordance with an application of the present invention, a method, including:
In an application, the method further includes, while the transducer remains secured in the blood vessel away from the vessel wall, and each electrode remains pressed against the vessel wall, driving the electrodes to apply an ablative radio-frequency current to the vessel wall.
In an application, the effector unit includes an expandable basket, the electrodes are disposed on the expandable basket, and the transducer is disposed inside the expandable basket, and expanding the effector unit includes expanding the expandable basket.
In an application, the effector unit includes a balloon, the electrodes are disposed on the balloon, and the transducer is disposed inside the balloon, and expanding the effector unit includes inflating the balloon.
In an application, the method further includes, while the transducer remains secured in the blood vessel away from the vessel wall, and each electrode remains pressed against the vessel wall, driving the electrodes to apply an excitatory current to the vessel wall.
In an application, the step of driving the electrodes to apply the excitatory current is performed before the step of operating the transducer to apply ultrasound.
In an application, the step of operating the transducer to apply ultrasound is performed in response to a detected blood pressure change in response to the applied excitatory current.
In an application, the method further includes detecting the blood pressure change.
There is further provided, in accordance with an application of the present invention, apparatus for use with a blood vessel of a subject, the blood vessel having a vessel wall, and the apparatus including:
In an application, the effector unit includes a plurality of electrodes including the electrode.
In an application, the plurality of electrodes is disposed circumferentially around the transducer in at least the expanded state of the expandable anchor.
In an application, the apparatus further includes a pressure sensor operable by the control circuitry, and the control circuitry is configured:
In an application, the control circuitry is configured to, in response to the received data and while the anchor is in the expanded state, operate the transducer to transmit ultrasound through the vessel wall at the longitudinal site.
There is further provided, in accordance with an application of the present invention, apparatus for use with a blood vessel of a subject, the blood vessel having a vessel wall, and the apparatus including:
In an application, the effector unit includes a plurality of electrodes including the electrode.
In an application, the plurality of electrodes is disposed circumferentially around the transducer in at least the expanded state of the expandable anchor.
Reference is made to
Extracorporeal controller 40 comprises a user interface 42 and control circuitry 44. User interface 42 may comprise a display and/or control elements such as buttons or knobs. For some applications, and as shown, controller 40 comprises a handle 46 in which control circuitry 44 and/or user interface 42 is disposed.
Effector unit 30 has a proximal end and a distal end, and defines a central longitudinal axis ax2 therebetween. Effector unit 30 is coupled to distal portion 22b of elongate member 22. In many situations, and as shown, axis ax2 of effector unit 30 is collinear with axis ax1 of distal portion 22b. Effector unit 30 has a contracted state (
In the expanded state of effector unit 30, each electrode is disposed further radially outward from (i) the central longitudinal axis of the effector unit, and (ii) the transducer, compared to when the effector unit is in the contracted state. In the expanded state of effector unit 30 (and typically also in its contracted state), the transducer is oriented to direct ultrasound radially outwardly, i.e., away from axis ax2.
As shown in the cross-section of
Typically, electrodes 32 are distributed circumferentially around axis ax2 also in the contracted state. For some applications, electrodes 32 are distributed circumferentially around (i.e., longitudinally aligned with) transducer 34 also in the contracted state (e.g., as shown in
Reference is now also made to
For some applications, balloon 58 or the fluid with which it is inflated further functions to cool the tissue with which it is in contact. The fluid with which balloon 58 is inflated is substantially acoustically transparent.
Reference is now made to
There is therefore provided, in accordance with some applications of the invention, apparatus comprising:
Electrodes 32 are used to locate (longitudinally and/or circumferentially) nerve tissue associated with vessel wall 10 in order to position transducer 34 for application of ablative ultrasound to the nerve tissue. For example, control circuitry 44 may be configured to drive one or more of electrodes 32 to apply excitatory current to vessel wall 10. If the driven electrodes are aligned with and/or close to the nerve tissue, the excitatory current initiates action potentials in the nerve tissue, resulting in a physiological response to the action potentials. The physiological response is therefore indicative that the driven electrodes, and therefore transducer 34, are positioned such that ablative ultrasound emitted by the transducer will be applied in an appropriate location. For some applications, a non-ablative blocking current is used instead of (or in addition to) the excitatory current.
Once an appropriate site has been located, transducer 34 is driven by control circuitry 44 to apply ablative ultrasound 60 to vessel wall 10, typically while electrodes 32 remain in contact with the site on the vessel wall at which they applied the current that identified the site (
For some applications, the excitatory current or non-ablative blocking current may alternatively or additionally be used to monitor the progress of ablation. After application of ablative ultrasound, the current may be (re)applied, and the physiological response (re)measured. A reduction in the physiological response correlates with successful ablation. For some applications, the excitatory current or non-ablative blocking current may be applied simultaneously with the ablative ultrasound, in order to monitor progress of ablation.
In response to this monitoring, the energy level and/or duration of ablation may be adjusted in real-time.
For applications in which system 20 is used for renal denervation, the physiological response that is measured is typically a change in blood pressure of the subject. For some applications, system 20 comprises a pressure sensor 48 (e.g., disposed on elongate member 22) that is operable by control circuitry 44, and the control circuitry is configured to, while the effector unit is in the expanded state, operate the electrodes to apply an excitatory current to the vessel wall, and to receive, from the pressure sensor, data indicative of a change in blood pressure of the subject in response to the excitatory current. For some such applications, control circuitry 44 is configured to, in response to the received data and while the effector unit is in the expanded state, operate (e.g., automatically operate) the transducer to transmit ultrasound 60. Alternatively, controller 40 is manually operated by a user to operate the transducer.
For some applications, the techniques used for using excitatory and/or non-ablative blocking current to locate nerve tissue and monitor progress of ablation are as described (mutatis mutandis) in one or more of the following references, which are incorporated herein by reference:
Reference is now made to
In
For some applications, the excitatory or non-ablative blocking current that is used to locate nerve tissue and/or monitor ablation progress is applied between adjacent electrodes 32. For such applications, the current therefore passes through the sector of vessel wall 10 disposed between these two electrodes, and may reach its maximum depth within the vessel wall midway along this sector. For example, in
It is hypothesized by the inventors that a configuration such as that shown in
For some applications, when effector unit 30′ is transitioned into its contracted state, electrodes 32 become disposed in the space circumferentially between transducers 34 (i.e., the electrodes intercalate with the transducers), such that a greatest diameter of the effector unit is smaller than a corresponding effector unit that has a fully circumferential transducer (e.g., effector unit 30). Therefore, for some applications, a method is provided in which an effector unit is transitioned from its contracted state into its expanded state by moving electrodes 32 radially outward from between transducers 34. For such applications, the user may also transition the effector unit from its expanded state into its contracted state by moving electrodes 32 radially inward to between transducers 34 (e.g., prior to introducing the effector unit into the body of the subject, or prior to withdrawal of the effector unit after treatment of the subject).
It is to be noted that although
As described hereinabove, although the figures of this patent application show the effector units as comprising four electrodes, they may comprise fewer (e.g., 1, 2, or 3) or more (e.g., 6, 8, or 12) electrodes. It is also to be noted that effector units such as effector unit 30′ may comprise fewer (e.g., 1, 2, or 3) or more (e.g., 6, 8, or 12) ultrasound transducers. For example, it is hypothesized by the inventors that for some applications it is advantageous for effector unit 30′ to comprise three electrodes and three transducers.
Reference is now made to
However, for some applications the transducer (e.g., a transducer 64) is oriented to transmit ultrasound 60 radially outward from axis ax2 at an angle alpha_1 that is less than 90 degrees from axis ax2. For some such applications, in at least the expanded state electrodes 32 are disposed distally (as shown in
Effector units 30 and 50 are shown as comprising a of four electrodes, but they may comprise fewer (e.g., 1, 2, or 3 electrodes) or more (e.g., 6, 8, or 12) electrodes. Effector units 30 and 50 are shown as comprising a single “ring” of electrodes, but they may alternatively comprise more than one ring of electrodes.
For some applications, ablative current (e.g., radio frequency (RF) current) may also be applied to the vessel wall, in order to ablate the nerve tissue. For some applications, the ablative current is applied by control circuitry driving electrodes 32 to apply the ablative current. For some applications, additional electrodes are provided on the effector unit for the application of the ablative current. For some applications, the ablative current is applied simultaneously with the ablative ultrasound. For some applications, the modality or modalities used is/are dependent on the depth of the nerve tissue within the vessel wall. For example, RF current may be used to ablate shallower nerve tissue, and ultrasound may be used to ablate deeper nerve tissue. Determination of the depth of nerve tissue to be ablated may be achieved using techniques described in one or more of the following references, which are incorporated herein by reference:
As used in the present application, including in the claims, a “central longitudinal axis” of an elongate structure (or portion thereof) is the set of all centroids of transverse cross-sectional sections of the structure along the structure (or portion thereof). Thus the cross-sectional sections are locally orthogonal to the central longitudinal axis, which runs along the structure (or portion thereof). (For a structure that is circular in cross-section, the centroids correspond with the centers of the circular cross-sectional sections.)
It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.