Patent Description:
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that results in obstructed airflow within the lungs, and the term is also used to refer to a family of pulmonary conditions, such as emphysema and chronic bronchitis. COPD is the fourth leading cause of death, with approximately one-third of all health-related expenses being associated with the condition. Asthma is believed to be a risk factor for developing COPD, and patients with COPD may be more likely to develop heart disease, lunch cancer, and other conditions. Research indicates that COPD causes epithelial metaplasia, mucous metaplasia, fibrosis, increase in smooth muscle mass, and other conditions that, in addition to the contractile nature of bronchial smooth muscle, contribute to airway obstruction. Additionally, bronchial smooth muscle in patients with COPD is infiltrated by inflammatory cytokines, proteases, and growth factors, which further exacerbates airway obstruction.

Denervation, or neural modulation, of the parasympathetic nervous system (PSNS) is a relatively new technique for treating conditions such as hypertension and cardiovascular disease in a minimally invasive way. However, there has been little research indicating the efficacy of denervation for other conditions, such as those affecting the lungs. Further, when performing denervation, care must be taken to avoid damaging non-target tissue. Documents <CIT>, <CIT>, <CIT> and <CIT> disclose relevant background art.

The invention is defined in the appended independent claim <NUM>. The methods disclosed hereafter are exemplary only and do not form part of the invention.

In the following description <NUM> inch equals to <NUM>,<NUM>.

Some embodiments advantageously provide devices, systems, and methods for treating pulmonary conditions, such as COPD, by denervating bronchial tissue using cryoablation. In one embodiment, a device for bronchial denervation comprises: an elongate body having a distal portion and a proximal portion opposite the distal portion; a treatment element at the distal portion of the elongate body; and a first recording electrode located distal to the treatment element and a second recording electrode located proximal to the treatment element, the first and second recording electrodes being configured to record electromyograms.

In one aspect of the embodiment, the treatment element includes at least one balloon. In one aspect of the embodiment, the treatment element includes an equatorial portion, the treatment element further including a fluid delivery element within the at least one balloon, the fluid delivery element having a plurality of orifices that are aligned with the equatorial portion of the treatment element. In one aspect of the embodiment, the plurality of orifices includes at least twenty-four orifices radially arranged about the fluid delivery element, each of the at least twenty-four orifices having a diameter of between approximately <NUM> inch and approximately <NUM> inch.

In one aspect of the embodiment, the at least twenty-four orifices are radially arranged about an entirety of a circumference of the fluid delivery element.

In one aspect of the embodiment, the at least twenty-four orifices are radially arranged about a portion of a circumference of the fluid delivery element.

In one aspect of the embodiment, the at least twenty-four orifices are helically arranged about an entirety of a circumference of the fluid delivery element.

In one aspect of the embodiment, the treatment element includes: a balloon having a plurality of lobes; and a plurality of splines extending parallel to the longitudinal axis of the elongate body, the plurality of splines alternating with the plurality of lobes.

In one embodiment, a system for bronchial denervation comprises: a cryoablation device including a treatment element and at least one recording electrode; an electromyography system in communication with the at least one recording electrode; and a control unit in fluid communication with the cryoablation device.

In one aspect of the embodiment, the cryoablation device further includes a longitudinal axis, the treatment element including: a balloon having a plurality of lobes; and a plurality of splines extending parallel to the longitudinal axis of the cryoablation device and between the plurality of lobes.

In one aspect of the embodiment, the treatment element includes a flexible portion that is transitionable between an at least substantially linear first configuration and an expanded second configuration, the flexible portion having a helical configuration when in the expanded second configuration.

In one aspect of the embodiment, the at least one recording electrode includes a first recording electrode located distal to the treatment element and a second recording electrode located proximal to the treatment element.

In one aspect of the embodiment, the electromyography system includes processing circuitry configured to: receive electromyogram signals from the at least one recording electrode; calculate a difference between a first electromyogram signal received from the first recording electrode and a second electromyogram signal received from the second recording electrode to generate a recorded electromyogram; and compare the recorded electromyogram to a reference electromyogram.

In one aspect of the embodiment, the processing circuitry is further configured to determine whether denervation has occurred in an area of targeted tissue proximate the treatment element based on the comparison between the recorded electromyogram and the reference electromyogram.

In one aspect of the embodiment, the processing circuitry is further configured to generate an alert when the processing circuitry has determined that denervation has occurred in the area of targeted tissue proximate the treatment element.

In one aspect of the embodiment, the control unit includes a coolant source, the coolant source being in fluid communication with the treatment element.

In one embodiment, a method for performing bronchial denervation comprises: positioning a treatment element of a cryoablation device within a bronchus of a patient's lung; expanding the treatment element such that at least a portion of the treatment element is in contact with at least a portion of at least one of bronchial tissue and nerves innervating the bronchial tissue; circulating coolant within the treatment element to reduce a temperature of the treatment element to a temperature sufficient to cryoablate the at least a portion of the at least one of bronchial tissue and nerves innervating bronchial tissue; recording at least one electromyogram signal from the at least a portion of the at least one of bronchial tissue and nerves innervating bronchial tissue with each of a first recording electrode and a second recording electrode; and transmitting the recorded at least one electromyogram signal to an electromyography system.

In one aspect of the embodiment, the method further comprises: calculating a difference between the at least one electromyogram signal received from the first recording electrode and the at least one electromyogram signal received from the second recording electrode to generate a recorded electromyogram; comparing the recorded electromyogram to a reference electromyogram; determining whether denervation has occurred in the at least a portion of the at least one of bronchial tissue and nerves innervating bronchial tissue based on the comparison; and discontinuing the circulation of coolant within the treatment element when it is determined that denervation has occurred in the at least a portion of the at least one of bronchial tissue and nerves innervating bronchial tissue.

In one aspect of the embodiment, the method further comprises: generating an alert when it is determined that denervation has occurred in the at least a portion of the at least one of bronchial tissue and nerves innervating bronchial tissue.

In one aspect of the embodiment, the treatment element includes at least one balloon, expanding the treatment element including inflating the balloon.

In one aspect of the embodiment, the at least one balloon includes: a balloon having a plurality of lobes; and a plurality of splines extending between the plurality of lobes.

Before describing in detail exemplary embodiments, it is noted that the embodiments reside primarily in combinations of apparatus components and processing steps related to performing a denervation procedure. Accordingly, the system and method components have been represented where appropriate by conventional symbols in the drawings, showing only those specific details that are pertinent to understanding the embodiments of the present disclosure so as not to obscure the disclosure with details that will be readily apparent to those of ordinary skill in the art having the benefit of the description herein. Moreover, while certain embodiments or figures described herein may illustrate features not expressly indicated in other figures or embodiments, it is understood that the features and components of the system and devices disclosed herein are not necessarily exclusive of each other and may be included in a variety of different combinations or configurations without departing from the scope of the invention.

The parasympathetic nervous system (PSNS), one branch of the autonomic nervous system, is involved in the parasympathetic control of the lungs. Activation of the PSNS causes postganglionic parasympathetic fibers to release acetylcholine, which results in constriction of the smooth muscle surrounding the bronchi and, in turn, the reduction of airflow. Denervation of the bronchi of the lung using cryoablation may be a safe and effective means for treating COPD and asthma. Many other larger nerves (for example, between <NUM> and <NUM>) are located within <NUM> of the inner surface of the bronchi. As discussed herein, cryoablating target nerve tissue in or along the bronchial wall radially outward from a tissue location may reduce airway resistance through the bronchus. Using cryoablation may minimize structural tissue damage in the bronchial wall of the airway while denervating parasympathetic nerve(s) around the bronchi and decreasing activity (and constriction) of the smooth muscle.

Referring now to <FIG>, an exemplary medical system <NUM> for bronchial denervation is shown. New research indicates that denervation within the lung using cryoablation is a safe and effective means for treating conditions such as COPD and asthma and, consequentially, for potentially reducing the risk of developing other conditions, such as heart disease and lung cancer. In one embodiment, the medical system <NUM> generally includes a treatment device, such as a cryoablation device <NUM>, having one or more treatment elements <NUM>, and a control unit <NUM> in communication with the cryoablation device <NUM>. In one embodiment, the medical system <NUM> also includes an electromyography system <NUM> in communication with the cryoablation device <NUM> and the control unit <NUM>. Although the cryoablation device <NUM> is described herein as operating to reduce the temperature of target tissue in order to ablate nerves within the lungs, it will be understood that the cryoablation device <NUM> also may be used with one or more additional modalities, such as radiofrequency (RF) ablation, pulsed field ablation, ultrasound ablation, microwave ablation, or the like. Additionally, the cryoablation device <NUM> may be used for treatment, denervation, or nerve modulation of other locations within the patient's body, such as the heart.

The one or more treatment elements <NUM> are configured to deliver cryogenic therapy, and may further be configured to deliver radiofrequency energy, pulsed field ablation energy, or the like for energetic transfer with the area of targeted tissue, such as pulmonary tissue. In particular, the treatment element(s) <NUM> are configured to reduce the temperature of adjacent tissue in order to perform cryotreatment and/or cryoablation and, consequently, denervation. For example, the treatment elements(s) <NUM> may include one or more balloons <NUM> (as shown in <FIG>) within which a coolant may be circulated in order to reduce the temperature of the balloon <NUM>. Additionally, the treatment element(s) <NUM> may include other thermally and/or electrically-conductive components, such as one or more electrodes in communication with the control unit <NUM> (not shown).

In the embodiment shown in <FIG> and <FIG>, the cryoablation device <NUM> includes a handle <NUM> and an elongate body <NUM> coupled to the handle <NUM>. The elongate body <NUM> is sized and configured to be passable through a patient's vasculature and/or positionable proximate to a tissue region for diagnosis or treatment, such as a catheter, sheath, or intravascular introducer. The elongate body <NUM> defines a longitudinal axis <NUM>, a proximal portion <NUM>, and a distal portion <NUM>, and may further include one or more lumens disposed within the elongate body <NUM> that provide mechanical, electrical, and/or fluid communication between the proximal portion <NUM> of the elongate body <NUM> and the distal portion <NUM> of the elongate body <NUM>. Further, the treatment element(s) <NUM> (such as the balloon(s) <NUM> shown in <FIG> and <FIG>) are coupled to the elongate body distal portion <NUM>. In one embodiment, the cryoablation device <NUM> further includes a shaft <NUM> that is longitudinal movable within a lumen of the elongate body <NUM>, such that the shaft <NUM> may be advanced or retracted within the elongate body <NUM>, and this movement of the shaft <NUM> may affect the shape and configuration of the treatment element(s) <NUM>. For example, the cryoablation device <NUM> may include one treatment element <NUM>, and the shaft <NUM> may be fully advanced when the treatment element <NUM> is deflated and in a delivery (or first) configuration wherein the treatment element <NUM> has a minimum diameter suitable, for example, for retraction of the cryoablation device <NUM> within a sheath for delivery to and removal from the targeted tissue site. Conversely, when the treatment element <NUM> is inflated or expanded and in a treatment (or second) configuration, the shaft <NUM> may be advanced or retracted over a distance that affects the size and configuration of the inflated or expanded treatment element <NUM>. Further, the shaft <NUM> may include a guidewire lumen through which a sensing device, mapping device, guidewire <NUM>, or other system component may be located and extended from the distal end of the cryoablation device <NUM> (for example, from the distal portion <NUM> of the shaft <NUM>). When expanded, the treatment element(s) <NUM> are sized and configured to fit within a targeted bronchus. For example, the expanded treatment element(s) <NUM> may have a maximum outer diameter of between approximately <NUM> and approximately <NUM> (± <NUM>).

In one embodiment, the treatment element <NUM> includes two balloons: an inner (or first) balloon 20A and an outer (or second) balloon 20B. However, it will be understood that the treatment element <NUM> may include any number of balloons. In the embodiment shown in <FIG>, a proximal portion of the treatment element <NUM> is coupled to the distal portion <NUM> of the elongate body <NUM> and a distal portion of the treatment element <NUM> is coupled to a distal portion <NUM> of the shaft <NUM>. The cryoablation device <NUM> also includes one or more nozzles, orifices, or other fluid delivery elements <NUM> for delivering fluid (for example, coolant) to an interior chamber <NUM> of the treatment element <NUM>. For example, fluid may be delivered to the interior chamber <NUM> of the inner balloon 20A and/or to the interior chamber of the outer cryoballoon 20B (that is, to the interstitial space <NUM> between the inner 20A and outer 20B balloons). For simplicity, coolant will be referred to herein as being delivered to the interior chamber <NUM> of the treatment element <NUM>. During operation, coolant may flow from a coolant supply reservoir <NUM> through a coolant delivery conduit within the elongate body <NUM> of the cryoablation device <NUM> to the distal portion <NUM>, where the coolant may then enter the interior chamber <NUM> of the treatment element <NUM>, such as through the one or more fluid delivery elements <NUM>, where the coolant may expand to cool the balloon(s) <NUM>. Expanded coolant may then pass from the interior chamber <NUM> of the treatment element <NUM> to a coolant recovery reservoir <NUM> and/or scavenging system through a coolant recovery conduit.

Referring now to <FIG>, exemplary embodiments of a cryoablation device <NUM> with at least one fluid delivery element <NUM> are shown. In one embodiment, the medical device <NUM> is generally as shown and described in <FIG> and <FIG>, and each fluid delivery element <NUM> includes a fluid delivery conduit that is wound or coiled about the shaft <NUM> at least once. In one non-limiting example, as shown in <FIG>, the cryoablation device <NUM> includes one fluid delivery element <NUM> that includes a plurality of orifices <NUM> in the coiled portion that are radially arranged about the fluid delivery element <NUM>, and in some embodiments the shaft <NUM>. In one non-limiting example, the fluid delivery element <NUM> includes twenty-four orifices <NUM>, or more, each orifice <NUM> having a diameter of between approximately <NUM> inch and approximately <NUM> inch, and the fluid delivery conduit has a diameter of between approximately <NUM> inch and approximately <NUM> inch. Further, the orifices <NUM> are located within a center swath or equatorial portion <NUM> of the treatment element <NUM> when the treatment element <NUM> is expanded. In one embodiment, the equatorial portion <NUM> corresponds to the portion of the balloon(s) <NUM> at which the balloon(s) <NUM> have the largest outer diameter when the balloon(s) <NUM> are inflated, such as when the balloon(s) <NUM> are fully inflated. Put one way, the equatorial portion <NUM> extends around the balloon(s) <NUM> of the treatment element <NUM> and the fluid delivery element(s) <NUM> are located within the treatment element <NUM> at a location that is aligned with the equatorial portion <NUM>. Put another way, the equatorial portion <NUM> lies in a cross-sectional plane of the treatment element <NUM> that includes the portion of the treatment element having the largest outer diameter, and the fluid delivery element(s) <NUM> are located within the equatorial portion <NUM>. Further, if the device includes two balloons <NUM>, in one embodiment the equatorial portion <NUM> of the first balloon 20A and the equatorial portion <NUM> of the second balloon 20B are in overlapping or overlaid positions such that the treatment element <NUM> as a whole defines the equatorial portion <NUM>. In another non-limiting example, as shown in <FIG>, the cryoablation device <NUM> includes a first fluid delivery element 38A and a second fluid delivery element 38B, each of which including a plurality of orifices <NUM> in the coiled portion that are radially arranged about the fluid delivery element, and in some embodiments the shaft <NUM>. In one non-limiting example, each fluid delivery element 38A, 38B includes twenty-four orifices <NUM>, or more, each orifice <NUM> having a diameter of between approximately <NUM> inch and approximately <NUM> inch and the fluid delivery conduit has a diameter of between approximately <NUM> inch and approximately <NUM> inch. The embodiments shown in <FIG> are in contrast to presently known devices, such as those used for atrial fibrillation treatment procedures, which typically include a fluid delivery element having eight orifices, each having a diameter of <NUM> inch. It will be understood that more than twenty-four orifices <NUM> may be used. Thus, in some embodiments, the device of the present disclosure includes at least one fluid delivery element <NUM> with more orifices <NUM> than presently known devices, and with each orifice <NUM> having a smaller diameter than presently known devices.

Continuing to refer to <FIG>, the orifices <NUM> of both fluid delivery elements 38A, 38B are located within a center swath or equatorial portion <NUM> of the treatment element <NUM> when the treatment element <NUM> is expanded, as discussed above regarding <FIG>. Put another way, the orifices <NUM> are co-axially or longitudinally aligned with the equatorial portion <NUM>. In one embodiment, the equatorial portion <NUM> includes the portion of the balloon(s) <NUM> at which the balloon(s) <NUM> have the largest outer diameter. Thus, during use, the coolant may be delivered to the portion of the balloon(s) <NUM> (and in some embodiments only to the portion of the balloon(s) <NUM>) that are, or are most likely to be, in contact with the targeted tissue. The configurations shown in <FIG> may cause coolant to be directed to the area(s) of the balloon(s) <NUM> (i.e. the equatorial portion <NUM>) that are most likely to create circumferential lesions in bronchial tissue to achieve bronchial denervation. Further, as each orifice <NUM> has a relatively small diameter, the increased number of orifices <NUM> and the placement of the orifices <NUM> within the equatorial portion <NUM> preserve cooling efficiently and total amount of coolant flow.

Referring now to <FIG>, further exemplary embodiments of fluid delivery elements are shown. In the embodiments shown in <FIG>, the fluid delivery element <NUM> is a plurality of orifices <NUM> within the shaft <NUM> (that is, extending through a wall of the shaft <NUM> from an outer surface to a lumen within the shaft <NUM>), rather than including a fluid delivery conduit wound about the shaft, as shown in <FIG>. However, it will be understood that the orifices <NUM> of the fluid delivery conduits <NUM> shown in <FIG> may have the configuration(s) shown in <FIG>. For example, in one embodiment the orifices <NUM> are radially arranged about an entirety of the circumference of the fluid delivery element <NUM> (such as in a configuration shown in <FIG>), in one embodiment the orifices <NUM> are radially arranged about a portion of the circumference of the fluid delivery element <NUM> (such as in a configuration shown in <FIG>), and in one embodiment the orifices <NUM> are helically or spirally arranged about at least a portion of the circumference of the fluid delivery element <NUM> (such as in a configuration shown in <FIG>). Likewise, the fluid delivery conduits <NUM> shown in <FIG> may include the number of orifices <NUM> and/or placement within the equatorial portion <NUM> of the balloon(s) <NUM> as discussed above regarding <FIG>.

In the embodiment shown in <FIG>, the fluid delivery element <NUM> is a plurality of orifices <NUM> within the shaft <NUM>, and the plurality of orifices <NUM> are arranged such that the orifices <NUM> circumscribe the shaft <NUM> at at least one location. In one embodiment, the plurality of orifices <NUM> are within a distal portion of the shaft <NUM> that is at least partially located within the balloon <NUM>. This configuration produces a circular fluid delivery pattern onto the inner surface of the balloon <NUM> (in one embodiment, onto the inner surface of the inner balloon 20A) to create a circular lesion in the bronchial tissue, such as that shown in <FIG>. In the embodiment shown in <FIG>, the fluid delivery element <NUM> is a plurality of orifices <NUM> within the shaft <NUM>, and the plurality of orifices <NUM> are arranged such that the orifices <NUM> partially circumscribe the shaft <NUM> at at least one location. In one embodiment, the orifices <NUM> extend around approximately half of the circumference of the shaft <NUM>, and produce a semi-circular fluid delivery pattern onto the inner surface of the balloon <NUM> (in one embodiment, onto the inner surface of the inner balloon 20A) to create a semi-circular lesion in the bronchial tissue, such as that shown in <FIG>. In the embodiment shown in <FIG>, the fluid delivery element <NUM> is a plurality of orifices <NUM> within the shaft <NUM>, and the plurality of orifices <NUM> are arranged such that the orifices <NUM> extend around the shaft <NUM> at least once in a helical or spiral arrangement at at least one location on the shaft <NUM>. This configuration produces a helical or spiral fluid delivery pattern onto the inner surface of the balloon <NUM> (in one embodiment, onto the inner surface of the inner balloon 20A) to create helical or spiral lesion in the bronchial tissue, such as that shown in <FIG>. Although the embodiments of <FIG> each include a plurality of orifices <NUM> within the shaft <NUM> (that is, extending through the shaft wall), it will be understood that the fluid delivery element <NUM> may have other shapes or configurations, such as a separate fluid delivery element <NUM> that wraps around shaft <NUM>, as shown in <FIG>, to produce the same fluid delivery patterns discussed herein.

In another embodiment, as shown in <FIG>, the treatment element <NUM> includes a plurality of splines <NUM> that are arranged about the elongate body longitudinal axis <NUM> and a single balloon <NUM> having a plurality of lobes <NUM> that are radially arranged about the elongate body longitudinal axis <NUM>, between the splines <NUM>. The splines <NUM> may be composed of a material that is less thermally conductive than the balloon <NUM>. In one embodiment, the lobes <NUM> are elongate and extend parallel to the elongate body longitudinal axis <NUM>. Alternatively, the treatment element <NUM> may include a plurality of individual balloons <NUM> radially arranged about the elongate body longitudinal axis <NUM> and between the splines <NUM>, each of the plurality of balloons <NUM> forming a lobe <NUM>. Alternatively, the treatment element <NUM> may include a single balloon <NUM> that is not manufactured or constructed with lobes but, when inflated, extends from the elongate body <NUM> in the areas between the splines <NUM> to create a plurality of lobed areas <NUM> of the treatment element <NUM>. In one embodiment, the lobes <NUM> and the splines <NUM> extend parallel to the elongate body longitudinal axis <NUM>. Unlike the balloons shown in <FIG>, both the distal portion(s) and the proximal portion(s) of the balloon(s) <NUM> (and the splines <NUM>) of the embodiment of <FIG> are coupled to the distal portion <NUM> of the elongate body <NUM>, and are not coupled to a shaft <NUM>. However, it will be understood that the cryoablation device <NUM> shown in <FIG> may include a shaft <NUM>, at least a portion of which is coupled to the balloon(s) <NUM> and/or the splines <NUM>. During use, coolant is circulated within the balloon(s) <NUM> to cool the balloon(s) to a temperature that is sufficient to cryoablate and, consequently, denervate adjacent targeted tissue.

In another embodiment, as shown in <FIG>, the treatment element <NUM> includes a flexible segment <NUM> that is transitionable between a delivery (or first) configuration in which the flexible segment <NUM> is in a linear, or at least substantially linear, configuration, and an expanded (or second) configuration in which the flexible segment <NUM> is in a helical (for example, as shown in <FIG>), spiral, curvilinear, or other configuration. The flexible segment <NUM> is composed of a thermally conductive material and includes one or more lumens or expansion chambers therein (referred to as the interior chamber <NUM>), such that coolant is circulated within the flexible segment <NUM> to cool the flexible segment <NUM> to a temperature that is sufficient to cryoablated and, consequently, denervate adjacent targeted tissue. In the embodiment shown in <FIG>, the flexible segment <NUM> is composed of a shape-memory material or a material that is biased toward the expanded configuration (or includes therein a shaping element, the shape of which controls the shape of the flexible segment <NUM>) such that the flexible segment <NUM> transitions from the delivery configuration to the expanded configuration when extended out of the elongate body <NUM> and/or a delivery sheath.

The cryoablation device <NUM> shown in <FIG> includes a shaft <NUM> slidably disposed within the elongate body <NUM> or coupled to the outside of, and slidably movable with respect to, the elongate body <NUM> (for example, as shown in <FIG>). In one embodiment, the shaft <NUM> is movably coupled to the elongate body <NUM> using one or more coupling elements <NUM>, such as rings, annular guides, or the like. Further, the flexible segment <NUM> includes a distal portion <NUM> that is fixedly coupled to both the shaft <NUM> and the elongate body distal portion <NUM>. Retraction of the shaft <NUM> within or relative to the elongate body <NUM> causes the flexible segment <NUM> to transition between the delivery configuration and the expanded configuration.

In either the embodiment of <FIG> or that of <FIG>, the flexible segment <NUM> has a size and shape of the bronchus to be treated. Further, the flexible segment <NUM>, when in the expanded configuration, may have a helical shape with any number of windings. In one embodiment, the flexible segment <NUM> includes one winding. In another embodiment, the flexible segment <NUM> includes a plurality of windings. However, it will be understood that the cryoablation device <NUM> may include a treatment element <NUM> of any suitable size, number, shape, or configuration for ablating tissue from within a bronchus of a lung.

In any embodiment, the cryoablation device <NUM> optionally may include at least two recording electrodes <NUM> capable of stimulating tissue, sensing, and/or recording electrical action potential signals from within the smooth muscle tissue of the bronchi. The recording electrode(s) <NUM> are in communication with and transmit signals to the electromyography system <NUM>, which interprets those signals and communicates them to the user, as is discussed in greater detail below. In one embodiment, the cryoablation device <NUM> includes a first recording electrode 56A located distal to the treatment element <NUM> and a second recording electrode 56B located proximal to the treatment element <NUM> (for example, as shown in <FIG>, <FIG>, and <FIG>). Each recording electrode <NUM> records the smooth muscle action potential, and the combined electromyogram signal represents a potential (voltage) difference between the action potentials recorded by the electrodes. In one embodiment, the first recording electrode 56A is coupled to the distal portion <NUM> of the flexible segment <NUM> and the second recording electrode 56B is coupled to the elongate body distal portion <NUM> (for example, as shown in <FIG>). In another embodiment, the first recording electrode 56A is coupled to the distal portion of the shaft <NUM> and the second recording electrode 56B is coupled to the shaft <NUM> at a location proximal to the first recording electrode 56A (for example, as shown in <FIG>). However, it will be understood that the recording electrodes <NUM> may be at any suitable location on the cryoablation device <NUM>.

Referring again to <FIG>, the electromyography system <NUM> includes one or more controllers, processors, and/or software modules containing instructions or algorithms to provide for the automated operation and performance of the features, sequences, or procedures described herein. In one embodiment, for example, the electromyography system <NUM> includes processing circuitry <NUM> with a memory and a processor. The memory is in electrical communication with the processor and includes instructions that, when executed by the processor, configure the processor to receive, process, or otherwise use signals from the cryoablation device <NUM> and/or other system components. Still further, the electromyography system <NUM> may include one or more user input devices, controllers, speakers, and/or displays <NUM> for collecting and conveying information from and to the user. Additionally or alternatively, the electromyography system <NUM> may be in communication with the control unit <NUM> such that information is received and/or communicated from the electromyography system <NUM> to the user through the control unit <NUM>.

In one non-limiting example, the processing circuitry <NUM> of the electromyography system <NUM> is configured to receive data (for example, electrical action potential signals) from the recording electrodes <NUM> of the cryoablation device <NUM> and to convert that data into information that can be conveyed to the user, such as a visual display, an audio signal, or the like. Further, the processing circuitry <NUM> of the electromyography system <NUM> may be configured to compare data received from the recording electrodes <NUM> to one or more reference values or ranges and generate an alert based on the comparison. For example, the processing circuitry of the electromyography system <NUM> may compare electrogram signal voltage and/or electromyogram signal amplitude over time (AOT) received from the recording electrodes to a threshold or reference electrogram signal voltage and/or electromyogram signal AOT that indicates denervation has occurred. If the received electromyogram signal voltage and/or AOT is within a threshold range of the reference electromyogram signal voltage and/or AOT, the processing circuitry may then generate and communicate an alert (such as a visual display or audio tone) to the user that indicates denervation has occurred and the user may cease the cryoablation procedure. Additionally, the processing circuitry <NUM> of the electromyography system <NUM> may be configured to calculate a time to denervation based on the difference between the received and the reference electromyography signal voltage and/or AOTs, so the user can know how much longer the cryoablation procedure should continue.

As used herein, the term "control unit" for simplicity may include any system components that are not part of the cryoablation device <NUM> itself, other than components of the electromyography system <NUM>, regardless of whether the component is physically located within or external to the control unit <NUM>. Further, the electromyography system <NUM> may be a standalone system in communication with the control unit <NUM> or may be contained within or integrated with the control unit <NUM>, even though it is shown as being physically separated from the control unit <NUM> in <FIG>. In one embodiment, the control unit <NUM> includes a coolant supply reservoir <NUM>, a coolant recovery reservoir <NUM> or an exhaust or scavenging system for recovering or venting expended fluid for re-use or disposal, as well as various control mechanisms. In addition to providing an exhaust function for the coolant supply, the control unit <NUM> may also include pumps, valves, controllers or the like to recover and/or re-circulate fluid delivered to the elongate body <NUM> and/or the fluid pathways of the system. Further, the control unit <NUM> may include a vacuum pump <NUM> for creating a low-pressure environment in one or more conduits within the cryoablation device <NUM> so that coolant is drawn into the conduit(s)/lumen(s) of the elongate body <NUM>, away from the distal portion <NUM> and towards the proximal portion <NUM> of the elongate body <NUM>.

In one embodiment, the control unit <NUM> includes one or more controllers, processors, and/or software modules containing instructions or algorithms to provide for the automated operation and performance of the features, sequences, or procedures described herein. In one embodiment, for example, the control unit <NUM> includes processing circuitry <NUM> programmed or programmable to execute the automated or semi-automated operation and performance of the features, sequences, calculations, or procedures described herein. In one embodiment, for example, the control unit <NUM> includes processing circuitry <NUM> with a memory and a processor. The memory is in electrical communication with the processor and includes instructions that, when executed by the processor, configure the processor to receive, process, or otherwise use signals from the cryoablation device <NUM> and/or other system components. Still further, the control unit <NUM> may include one or more user input devices, controllers, speakers, and/or displays <NUM> for collecting and conveying information from and to the user.

Although not shown, the medical system <NUM> may include one or more sensors to monitor the operating parameters through the medical system <NUM>, such as pressure, temperature, coolant flow rate, or the like. The sensor(s) may be in communication with the control unit <NUM> for initiating or triggering one or more alerts or coolant delivery modifications during operation of the cryoablation device <NUM>.

Referring now to <FIG>, with reference to <FIG>, an exemplary method of performing bronchial denervation using a cryoablation device <NUM> is shown. In a first step <NUM>, a treatment element <NUM> of a cryoablation device <NUM> is positioned within a bronchus <NUM> of the patient's lung at a location proximate a targeted area of tissue (for example, as shown in <FIG>). In a second step <NUM>, the treatment element <NUM> of the cryoablation device <NUM> is inflated, expanded, or otherwise manipulated such that at least a portion of the treatment element <NUM> is brought into contact with at least a portion of the targeted area of tissue.

In a third step <NUM>, the recording electrodes <NUM> are positioned such that they are in contact with the targeted area of tissue and are used to record electromyogram signals (smooth muscle action potential signals) from the targeted area of tissue. Further, the electrogram signals may be recorded by the recording electrodes before, during, and/or after a cryoablation procedure. Thus, the third step <NUM> may occur at any time during the method.

In a fourth step <NUM>, coolant is delivered from the coolant supply reservoir <NUM> to the treatment element <NUM> and circulated within the treatment element <NUM> to reduce the temperature of the treatment element <NUM> to a temperature sufficient to cryoablate tissue that is in contact with the treatment element <NUM>. As noted above, the recording electrodes <NUM> may continue to record electromyogram signals from the bronchial tissue over the time during which coolant is circulated within the treatment element <NUM> (that is, during the cryoablation procedure). This is indicated as step <NUM> in <FIG>; however, it will be understood that this step may be performed at the same time as, before, and/or after the fourth step <NUM>. Non-limiting examples of ablation patterns created within bronchial tissue by a treatment element <NUM> are shown in <FIG>. For example, using a treatment element <NUM> such as that shown and described in <FIG> and <FIG> (that is, at least one balloon <NUM> without lobes) that has, in one embodiment, a fluid delivery element <NUM> with a circular fluid delivery pattern (as shown in <FIG>), may create a circumferential lesion 68A within the bronchial tissue <NUM>, a stylized representation of which is shown in <FIG>; using a treatment element <NUM> such as that shown and described in <FIG> and <FIG> that has, in one embodiment, a fluid delivery element <NUM> with a semi-circular fluid delivery pattern (as shown in <FIG>), may create a partially circumferential or semi-circular lesion 68B (for example, a semi-circular lesion) within the bronchial tissue <NUM>, a stylized representation of which is shown in <FIG>; using a treatment element <NUM> such as that shown and described in <FIG> (that is, a balloon with lobes <NUM> or several balloons forming lobed areas <NUM>) may create a series of lesions 68C within the bronchial tissue <NUM>, a stylized representation of which is shown in <FIG>, or an interrupted circumferential lesion such as that shown in <FIG>; and using a treatment element <NUM> such as shat shown and described in <FIG> (that is, a flexible segment <NUM> transitionable to a helical configuration) or a treatment element <NUM> such as that shown and described in <FIG> and <FIG> that has, in one embodiment, a fluid delivery element <NUM> with a spiral or helical fluid delivery pattern (as shown in <FIG>) may create a helical lesion 68D in the bronchial tissue <NUM>, a stylized representation of which is shown in <FIG>.

Here, the third step <NUM> may again be performed. The electromyogram signals are transmitted from the recording electrodes <NUM> to the electromyography system <NUM>. Additionally, these signals may be continually recorded and transmitted before, during, and after the cryoablation procedure. The processing circuitry <NUM> of the electromyography system <NUM> then uses the received electromyogram signals to make one or more comparisons and determinations (thus, the received electromyogram signals may be referred to as being raw electromyogram signals). For example, in a fifth step <NUM>, the processing circuitry <NUM> of the electromyography system <NUM> calculates a difference between at least one electromyogram signal received from a first recording electrode 56A and at least one electromyogram signal received from a second recording electrode 56B. In one non-limiting example, the processing circuitry <NUM> of the electromyography system <NUM> calculates a voltage difference between received or raw electrogram signals transmitted from the recording electrodes during the cryoablation procedure and generates a recorded electromyogram <NUM>. Thus, the recorded electromyogram <NUM> includes voltage difference(s) over time. For example, <FIG> shows a recorded electromyogram 70A recorded before denervation occurs (that is, recorded before the cryoablation procedure and/or during the cryoablation procedure, before denervation occurs). As noted above, the recording electrodes <NUM> may continue to record electrogram signals during and/or after the cryoablation procedure, and the processing circuitry <NUM> of the electromyography system <NUM> may continue to generate recorded electromyograms <NUM>.

Further, in one embodiment, the processing circuitry <NUM> of the electromyography system <NUM> is configured to compare a recorded electromyogram <NUM> generated from electromyogram signals received before the cryoablation procedure with a recorded electromyogram <NUM> generated from electromyogram signals received during and/or after the cryoablation procedure, and to use this comparison to determine whether denervation of the bronchial tissue <NUM> has occurred (such as in a sixth step <NUM>). In one non-limiting example, if the difference in recorded electromyograms (such as a voltage difference) exceeds a threshold difference, the processing circuitry <NUM> of the electromyography system <NUM> may determine that denervation has occurred (such as in a seventh step <NUM>). Additionally or alternatively, the processing circuitry <NUM> electromyography system <NUM> is configured to compare a recorded electromyogram <NUM> generated from electromyogram signals received during and/or after a cryoablation procedure with a reference electromyogram that indicates denervation has occurred. If the recorded electromyogram <NUM> is the same as, or is within a threshold range or difference of, the reference electromyogram, the processing circuitry <NUM> of the electromyography system <NUM> may determine that denervation has occurred (such as in a seventh step <NUM>). For example, <FIG> shows a recorded electromyogram 70B after denervation has occurred, in which the attenuated electromyogram voltage is shown.

In an eighth step <NUM>, the processing circuitry <NUM> of the electromyography system <NUM> generates an alert when it determines that denervation has occurred. In one non-limiting example, the electromyography system <NUM> generates an audible and/or visual alert that communicates to the user that denervation has occurred and gives the user the opportunity to discontinue the cryoablation procedure (for example, to discontinue or reduce the circulation of coolant within the treatment element <NUM>). Additionally or alternatively, the electromyography system <NUM> generates an alert in the form of alert data and transmits this data to the control unit <NUM>. The control unit <NUM> may then communicate the alert (for example, audible and/or visual alert) to the user to prompt the user to manually discontinue the cryoablation procedure, and/or the control unit <NUM> may automatically discontinue or reduce the circulation of coolant within the treatment element <NUM> to end the cryoablation procedure.

Claim 1:
A system for bronchial denervation, the system (<NUM>) comprising:
a medical device (<NUM>) including:
an elongate body (<NUM>) having a distal portion (<NUM>), a proximal portion (<NUM>) opposite the distal portion, and a longitudinal axis (<NUM>);
a treatment element (<NUM>) at the distal portion (<NUM>) of the elongate body (<NUM>); and
at least one recording electrode (<NUM>) configured to record electromyograms;
an electromyography system (<NUM>) in communication with the at least one recording electrode (<NUM>); and
a control unit (<NUM>) in communication with the medical device, wherein the at least one recording electrode (<NUM>) includes a first recording electrode (56A) located distal to the treatment element and a second recording electrode (56B) located proximal to the treatment element, the electromyography system (<NUM>) including processing circuitry (<NUM>) configured to:
receive electromyogram signals from the first recording electrode (56A) and the second recording electrode (56B),
characterized in that the processing circuitry (<NUM>) is further configured to:
calculate a difference between a first electromyogram signal received from the first recording electrode (56A) and a second electromyogram signal received from the second recording electrode (56B) to generate a recorded electromyogram; and
compare the recorded electromyogram to a reference electromyogram to determine whether denervation has occurred in the at least a portion of bronchial tissue based on the comparison.