Patent ID: 12256983

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Exemplary embodiments of the present disclosure are described with reference to the accompanying drawings in detail. The same reference numbers are used throughout the drawings to refer to the same or like parts. Detailed descriptions of well-known functions and structures incorporated herein may be omitted to avoid obscuring the subject matter of the present disclosure.

Components, or nodes, shown in diagrams are illustrative of exemplary embodiments of the invention and are meant to avoid obscuring the invention. It shall also be understood that throughout this discussion that components may be described as separate functional units, which may comprise sub-units, but those skilled in the art will recognize that various components, or portions thereof, may be divided into separate components or may be integrated together, including integrated within a single system or component.

Reference in the specification to “one embodiment,” “preferred embodiment,” “an embodiment,” or “embodiments” means that a particular feature, structure, characteristic, or function described in connection with the embodiment is included in at least one embodiment of the invention and may be in more than one embodiment. The appearances of the phrases “in one embodiment,” “in an embodiment,” or “in embodiments” in various places in the specification are not necessarily all referring to the same embodiment or embodiments.

The terms and words used in the following description and claims are not limited to the bibliographical meanings, but, are merely used by the inventor to enable a clear and consistent understanding of the present disclosure.

In the present disclosure, the terms such as “include” and/or “have” may be construed to denote a certain characteristic, number, step, operation, constituent element, component or a combination thereof, but may not be construed to exclude the existence of or a possibility of addition of one or more other characteristics, numbers, steps, operations, constituent elements, components or combinations thereof.

Several embodiments of the present disclosure described herein relate generally to apparatus, systems and methods for therapeutically effecting neuromodulation (e.g., nerve disruption, nerve denervation, nerve stimulation) of target nerve to treat various medical conditions, disorders and diseases. In embodiments, neuromodulation of the target nerve may be used to treat or reduce the risk of occurrence of symptoms associated with a variety of metabolic diseases. For example, neuromodulation of the target nerve may treat or reduce the risk of occurrence of symptoms associated with hypertension or other hypertension-related diseases, diabetes or other diabetes-related disease. If human patient has a vascular diseases, such as hypertension, the methods described herein may advantageously treat hypertension without taking hypertension drugs and if human patient has diabetes mellitus, the methods described herein may advantageously treat diabetes without requiring daily insulin injection or constant monitoring of blood glucose levels. The treatment provided by the apparatus, systems and methods described herein may be permanent or at least semi-permanent, thereby reducing the need for continued or periodic treatment.

In embodiments, neuromodulation of the target nerve as described herein may be used for the treatment of insulin resistance, genetic metabolic syndromes, ventricular tachycardia, atrial fibrillation or flutter, arrhythmia, inflammatory diseases, hypertension, obesity, hyperglycemia, hyperlipidemia, eating disorders, and/or endocrine diseases.

The neuromodulation of the target nerve is not limited to the disease treatment described above and can be used to treat other suitable types of diseases that one skilled in the art appreciates or recognizes.

FIG.1illustrates a common human renal anatomy. As depicted, the kidneys K are supplied with oxygenated blood by renal arteries RA, which are connected to the heart by the abdominal aorta AA. Deoxygenated blood flows from the kidneys to the heart via renal veins RV and the inferior vena cava IVC.

FIG.2Aillustrates a portion of human renal artery.

RA and renal nerves RN.FIG.2Billustrates a cross-sectional view taken along the radial plane A-A ofFIG.2A.

As depicted, the renal artery RA has a lumen through which the blood B flows. The renal nerves RN are located in proximity to the adventitia of the renal artery ARA and run along the renal artery RA in a lengthwise direction L. More specifically, renal nerves RN are situated in a circumferential tissue5surrounding the outer wall of the renal artery RA and the circumferential tissue5may include other tissue, such as lymphatics and capillaries.

In the conventional approaches based on applying denervation energy to destroy the renal nerves RN, a catheter is inserted into the lumen and delivers heat energy to denervate the target renal nerves RN. During this process, the denervation energy may damage the adventitia ARA of renal artery RA before it reaches the renal nerves RN. Furthermore, a portion of the denervation energy may be absorbed by the adventitia of the renal artery ARA, reducing the efficiency in utilizing the energy. Accordingly, it may be more effective and safer to denervate from outside of the renal artery RA (i.e., apply energy from outside of RA) than to denervate from inside of the renal artery RA (i.e., apply energy from inside of RA).

FIG.3is a schematic block diagram of a catheter system300for renal denervation according to embodiments of the present invention. As depicted, the catheter system300includes: a catheter apparatus100having a distal portion11which may make a contact with a target tissue and/or be disposed in proximity to the target tissue for treatment; a control unit200for controlling one or more components of the system300; an energy source generator (ESG)205for supplying energy to the target tissue through the distal portion11of the catheter apparatus100; an imaging system207for processing visual images and displaying the images to the users; and wires/cables/buses204that connect the components of the system300to each other for communication. In the present disclosure, the target tissue is described as the renal artery nerves, but it should be apparent to those of ordinary skill in the art that the target tissue means various artery nerves, such as renal artery nerves, hepatic artery nerves, splenic artery nerves and pulmonary artery nerves.

The control unit200may collectively refer to one or more components for controlling various components of the catheter system300. In embodiments, the control unit200may include a digital signal processor (DSP)201, such as CPU, and a memory203. The memory203may store various data and include, but are not limited to: magnetic media such as hard disks, floppy disks, and magnetic tape; optical media such as CD-ROMs and holographic devices; magneto-optical media; and hardware devices that are specially configured to store or to store and execute program code, such as application specific integrated circuits (ASICs), programmable logic devices (PLDs), flash memory devices, and ROM and RAM devices.

In embodiments, a data logger224may be included in the memory203and store data (e.g., temperature of the target tissue) measured by the catheter100during the denervation procedure. It is note that the memory203may be located outside the control unit200and coupled to the control unit200via a wire/cable204.

It is noted that the control unit200may be a computer, a server, or any other suitable computing facility and include other components, such as printer, input device (such as keyboard and mouse), scanner, display device, and a network interface.

In embodiments, the distal portion11may include denervation element(s) and optionally an endoscope or some other type of imaging device, coupled to an imaging system207, to provide images of the target tissue using suitable imaging techniques. The imaging device may allow the operator/physician to visually identify the region being ablated/denervated, to monitor the progress of the ablation/denervation in real time, and to address safety concerns during operation.

FIG.4is a side elevational view of a catheter apparatus100according to embodiments of the present invention. As depicted, the catheter apparatus100comprises a shaft10, a loop20, a holder30, a slider35, a butt50, a handle70and a loop control90.

The shaft10has a proximal end13coupled to the holder30and a distal end15removably connected to the distal portion11of the catheter apparatus100. The shaft10has a shape of tube, forming a channel that extends from the proximal end13to the distal end15, and is dimensioned to allow a stylet and/or a wire(s) to pass therethrough. The distal portion11may form a passage through which the loop20travels, as explained in detail below.

In embodiments, the shaft10may be made of silicone, polyurethane (PU), Pebax, or a combination of PU and silicone, or some other biocompatible polymers and/or metallic materials. The shaft10may be sufficiently large enough to house an imaging device, such as an endoscope, as well as components for ablation/denervation. In embodiments, the shaft10may include electrical wires/cables that run from the energy source generator204to the electrodes on the loop20. In embodiments, the shaft10may include wires/cables for providing electrical energy to the endoscope and transmitting visual images from the endoscope to the control unit200. In embodiments, the shaft10may be dimensioned to provide safe and easy treatment of the target tissue with minimal percutaneous access site on the patient, for example, on the abdominal region.

In embodiments, the loop20may be removably coupled to the distal end15of the shaft10and mechanically connected to the shaft10.

The holder30is connected to the proximal end13of the shaft10. More specifically, the holder30may have a structure for accepting the proximal end13of the shaft10therein and be electrically coupled to the proximal end13. In embodiments, a slider35may be rotatably coupled to the holder30and the operator may rotate the slider35to engage (or disengage) the shaft10to (or from) the holder30.

In embodiments, the holder30may include the butt50and a terminal51disposed on one side of the butt50. The terminal51may receive various types of energy from the energy source generator205via the wire/cable204and the energy is delivered from the terminal51to the loop20via suitable wires/cables running through the shaft10. In embodiments, the energy may be, but not limited to, at least one of a radio-frequency (RF) energy, electrical energy, laser energy, ultrasonic energy, high-intensity focused ultrasound (HIFU) energy, cryogenic energy, and thermal energy. Energy may be delivered to the loop20, simultaneously or sequentially, or selectively. For selective delivery, a clinician can select, via a user interface of the energy source generator205, such as an RF generator, a specific electrode to be utilized in the denervation process, where the electrode is disposed in the loop20.

The handle70may extend from the butt50. The handle may have a vacant space (hole) into which the operator may insert his finger(s) to have a firm grip of the holder30.

A push-button61may be disposed on another side of the butt50or one side of the handle70. The push-button61is operated by the operator to control the energy flow to the loop20.

The loop control90may be hinged on the butt50or the handle70. The loop control90may also have a vacant space (hole) in which the operator's thumb can be inserted. As described below, the operator may control the loop control90to coil/uncoil the loop20.

FIG.5illustrates an example of an operation of a catheter according to an embodiment of the present invention. As shown in theFIG.5, the slider35may be rotated up to about 360 degrees about the longitudinal axis A of the shaft10. A rotational direction of the slider35may be bidirectional or unidirectional. As the slider35rotates, as indicated by the arrows92, the loop20may also rotate around the longitudinal axis A of the shaft10, as indicated by the arrows90. Thus, a rotation of the loop20about the longitudinal axis of the shaft10may be controlled by the rotation of the slider35.

In embodiments, when moved forward/backward (or upward/downward) by the operator's finger, as indicated by arrows94, the loop control90mechanically controls the loop20, where the loop control90may be designed to operate in various modes. In one mode, as the loop control90moves forward (or downward), the loop20, which is originally rolled, may be unrolled to a straight segment and extend along the longitudinal axis A of the shaft10. As the loop control90moves backward (or upward), the loop20is rolled to its original shape. In this mode, the operator may bring the loop20near the target tissue or renal artery RA and move the loop control90backward to curl the loop20around the target tissue or renal artery RA.

In another mode, the loop20may be retracted into the shaft10. As the loop control90is moved forward (or downward), the loop20may emerge from the distal portion11and become a straight segment or curl into a semi-circle. As the loop control90is moved backward (or upward), the loop20may curl around the target tissue or renal artery RA.

FIG.6AtoFIG.6Dshow a loop that curls as it emerges from the shaft10of the catheter apparatus according to embodiments of the present invention. As depicted, the loop20includes a body21and one or more electrodes23disposed on the body21. The loop20may remain inside the shaft10and distal portion11(retracted position) when the loop control90is in the neutral position. As the operator moves the loop control90forward (or downward), the loop emerges from the distal portion11, forming a curved segment. As depicted inFIG.6A to6D, the loop20curls as the tip of the loop20proceeds from the position60toward the position64.

In embodiments, the body21may be made of a flexible material. In embodiments, the body21may be made of thermally non-conductive elastic material so that the energy delivered to the electrodes23is localized only to a portion(s) of the tissue that the electrodes23contact. As the localized energy is used to denervate the renal nerves RN (shown inFIG.3), the potential damage caused by the loop20to the tissue nearby the renal nerves RN may be significantly reduced during operation.

In embodiments, the loop20may be flexible and deformable to curl around a renal artery as discussed in conjunction withFIG.8. The loop20may be designed for two different operational modes. In the first mode, the loop20may remain flat when the loop20is brought into proximity to the target tissue, such as the circumferential tissue5of the renal artery. Then, the operator may manipulate the loop control90to curl the loop20around the circumferential tissue5and perform denervation. Upon completing the denervation, the operator may release the loop control90to uncurl loop20. In the second mode, the loop20may remain curled when the distal portion11is brought into proximity to the target tissue. Then, the operator may manipulate the loop control90to uncurl the loop20, position the loop20around the target tissue, release the loop control90to curl the loop20around the renal artery and perform denervation.

In embodiments, the electrodes23may be disposed on the inner side of the body21so that the electrodes23may contact the circumferential tissue5when the loop20curls around the circumferential tissue5. In embodiments, the electrodes23may extend along the longitudinal direction of the body21and be arranged in parallel to each other. In one embodiment, the body21may be formed of dielectric material and the electrodes23may be formed on the inner surface of the body21. In embodiments, the body21may have a groove or a channel on the inner surface of the body21and the electrodes23may be formed by filling electrically conductive material in the groove or the channel.

In another embodiment, the body21may be formed of electrically conducting material and the entire surface of the body21may be covered with dielectric material except the location where the electrodes23are to be located. In embodiments, a dielectric body may be disposed between the two electrodes23to electrically isolate the electrodes23from each other.

In embodiments, the electrodes23may be formed of electrically-conductive elastic material so that they can deform along with the body21as the body21is curled/uncurled. In embodiments, the electrodes23may contact the circumferential tissue5surrounding the outer surface of the renal artery and generate heat energy when electrical energy, such as RF energy, is supplied, where the heat energy may be used to denervate the renal nerve RN.

InFIG.6A to6D, only two electrodes23are shown. However, it should be apparent to those of ordinary skill in the art that any suitable number of electrodes may be used. For instance, if the electrical energy is supplied as unipolar energy, a single electrode may be used. In another example, if the electrical energy is supplied as bipolar energy, two or more electrodes may be used.

FIG.7A to7Dshow a loop400according to embodiments of the present invention. As depicted, the loop400is similar to the loop20, with the difference that a sensor425is mounted to the body421. In embodiments, the sensor425and the electrodes423may be disposed on the inner side of the body421.

In embodiments, the sensor425may be mounted in the body421formed of dielectric material so that the sensor425may be electrically insulated from the electrode423. The electrodes423and sensor425may move along the body421when the loop420curls/uncurls around the target tissue.

When the electrode(s)423and the sensor425curl around the circumferential tissue5of the renal artery, in embodiments, the electrode(s)423and the sensor425contact the circumferential tissue5. For instance, the electrode(s)423may receive electrical energy such as RF energy and generate heat energy. The sensor225may measure the impedance of the electrodes423or the temperature of the circumferential tissue. The sensor425may be connected to the central controller200via a wire(s) that run through the catheter apparatus100, where electrical power for the sensor425may be also delivered via a wire(s).

Information of the measured impedance or temperature may be transmitted to the memory203of the catheter system300. In embodiments, the operator may diagnose the denervation process using the information. The power for delivering thermal energy may also be automatically controlled by the energy source generator205or the central controller200based on the information. It is noted that other types of sensor may be used to measure various quantities, where each quantity may indicate the status of the denervation process and provide guidance to the physician during operation.

FIG.8is a schematic diagram of a catheter, illustrating renal denervation using the catheter according to embodiments of the present invention.

As shown inFIG.8, the distal portion11of the catheter is advanced into proximity of the patient's renal artery RA. The operator may operate the loop control90so that the loop20(or420) including a plurality of electrodes23(or423) may curl around the circumferential tissue5of the renal artery to thereby directly or indirectly contact the circumferential tissue of the renal artery RA. The electrodes23(or423) may be positioned on a circumferential treatment zone along a segment of the renal artery RA. The electrodes23(or423) may include a first electrode to deliver thermal energy to a first treatment zone of the renal artery RA a second electrode to deliver thermal energy to a second treatment zone of the renal artery RA.

In embodiments, each of the electrodes may deliver thermal energy to a different treatment zone, respectively or deliver thermal energy to the same treatment zone.

In embodiments, the loop20(or420) may be electrically coupled to energy source generator205for delivery of a desired electrical energy to the electrodes (or423). In embodiments, the electrical energy may be thermal RF energy using Quantum Molecular Resonance (QMR). A frequency of the RF energy may be higher than or equal to 4 MHz and may destruct at least a portion of the circumferential tissue5of the renal artery RA. In embodiments, the temperature range of the electrodes23(or423) during operation ranges from 60 degrees to 70 degrees.

In embodiments, the loop20(or420) may supply electrical energy to the circumferential tissue5of the renal artery RA to cause renal denervation through the electrode23(or423). The heat energy, which is generated by the electrodes23(423), may destruct a portion of the circumferential tissue of the renal artery, where the circumferential tissue may include at least one of a renal nerve RN, lymphatics and capillaries. This may be achieved via contact between the loop20(or420) and the circumferential tissue5of the renal artery RA. In embodiments, during the denervation, an impedance of the electrode or a temperature of the circumferential tissue may be measured using the sensor425.

FIG.9is a flow chart900illustrating exemplary steps that may be carried out to denervate renal nerves according to embodiments of the present invention. The process starts at step902. At step902, the loop20(or420) that is positioned near a target tissue, such as circumferential tissue5of the renal artery RA. In embodiments, the loop (or420) may include one or more electrode23(or423). Next, at step904, the loop20(or420) may be curled around the target tissue.

At step906, energy may be delivered to the electrode23, where the electrode23may convert the energy into heat energy. Then, at step908, at least a portion of the target tissue may be denervated by the heat energy.

FIG.10is a perspective view of a distal end portion of the catheter inFIG.4according to embodiments of the present invention.FIG.10also includes a cross sectional view of the loop, taken along the line53-53, according to embodiments of the present invention.

As depicted, the loop20includes a body21, one or more electrodes23disposed on a surface of the body21and a substrate25embedded in the body21and separated from the electrodes23by a certain distance.

The body21may be made of insulating/elastic materials, such as silicon. The electrodes23may extend along the longitudinal direction of the body21and may be made of shape-memory alloy, such as Nitinol. The substrate25may also extend along the longitudinal direction of the body21like the electrodes23and may be made of the same material as the electrode. The substrate25may be electrically insulated from the electrodes23. In embodiments, the substrate25may be electrically coupled to the energy source generator205via a switch (not shown) and may receive electrical energy from the energy source generator205.

If the substrate25is not included in the body21, a portion of the heat energy generated by the electrode23may be transferred toward the backside surface54of the body21, as indicated by the arrows56. The substrate25may prevent the heat energy56from being transferred to a tissue on the backside surface54of the body21while most of the heat energy generated by the electrodes is transferred to the target tissue on the front side surface of the body21. As a result, the thermal efficiency of the loop20may be increased.

The substrate25may have a width W1wider than the width W2of each of the electrodes23to more efficiently prevent energy transfer to the tissue that is on the backside surface54of the body21.

In embodiments, the backside surface54of the body21may be coated with a thermally insulating material to block a transfer of the heat energy56.

FIG.11AandFIG.11Bshow the loop inFIG.10at two different temperatures according to embodiments of the present invention.

Referring toFIG.11A, the loop20curls around the circumferential tissue5(e.g., renal artery) as the tip of the loop20proceed from the position60toward the position64as depicted inFIG.6A to6D. In other words, the operator may mechanically manipulate the loop control90to curl the loop20around the circumferential tissue5regardless of the temperature of the loop20. In some cases, the electrodes may firmly contact the circumferential tissue when the loop curls around the circumferential tissue by the operator's manipulation. In other cases, the electrodes of the curled loop may not firmly contact the circumferential tissue for various reasons, such as reduction in the mechanical elasticity of the loop due to the mechanical fatigue developed by repeated usage of the loop20, reduction in the mechanical force to tighten the loop and so on.

Referring toFIG.11B, the electrodes and/or the substrate may be made of shape-memory alloy whose shape changes at a critical temperature. In embodiments, as described in conjunction withFIG.12, the electrodes23(or substrate25) made of the shape-memory alloy may be curved at a first curvature at a low temperature (i.e., below the critical temperature) and return to its pre-deformed shape (i.e., curved at a second curvature) when heated above the critical temperature so that the loop20curls tightly around the circumferential tissue5. For example, the critical temperature may range between 35° C. and 45° C.; preferably, the critical temperature point may be the body temperature of the patient.

As discussed above, the energy delivered to the electrodes23or substrate25may include one or more of radio-frequency (RF) energy, electrical energy, laser energy, ultrasonic energy, high-intensity focused ultrasound (HIFU) energy, cryogenic energy, and thermal energy. The critical temperature of the shape-memory alloy that the electrodes23(or substrate25) is made of may be reached in two ways. The first way may be that the critical temperature is reached by the energy delivered to the electrodes23and the second way may be that the critical temperature is reached by the energy delivered to the substrate23. More specifically, in the case of the first way, the energy is delivered to the electrodes23, causing the temperature of the electrodes to rise due to the heat energy generated by the electrodes23. Also, a portion of the heat energy is transferred to the substrate25, causing the temperature of the substrate25to rise to the critical temperature. As the temperature of the substrate25reaches the critical temperature, the substrate25may curl more tightly around the target tissue as the shape-memory alloy of the substrate25may return to the pre-deformed state. The loop20including the substrate25may curl more tightly around the target tissue so that the electrodes23included to the loop may firmly contact the circumferential tissue, as depicted inFIG.11B. In the case of the second way, the energy is directly delivered to the substrate25so that the temperature of the substrate25rises due to the heat energy generated by the substrate. As the temperature of the substrate25reaches the critical temperature, the substrate25may curl more tightly around the target tissue as the shape-memory alloy of the substrate25returns to the pre-deformed state. The loop20including the substrate25may curl tightly around the target tissue so that the electrodes23included to the loop20may firmly contact the circumferential tissue, as depicted inFIG.11B.

As described above, the electrodes23may firmly contact the circumferential tissue by either of the two ways, and as a consequence, the renal denervation may be performed more efficiently.

FIG.12shows a deformation of the substrate25inFIG.10in response to a temperature change according to embodiments of the present invention.

As depicted inFIG.12, at least a portion of the flat substrate is formed of shape-memory alloy and is deformed to different loops depending on its own temperature. In the first mode, when the temperature (T1) of the substrate25is less than the critical temperature (Af) (i.e., no energy is delivered to the electrodes23or the substrate25), a portion of the substrate25may be curled by manipulating the loop control90. At this time, the first circular loop of the substrate25may be formed by a mechanical bending force that may be applied by the operator's manipulation, where the first diameter (R1) of the first circular loop is large enough to curl around the tissue. In embodiments, the first circular loop of the substrate25may be formed by delivering the energy to the electrodes23or the substrate25while the temperature of the substrate25is below the critical temperature.

In the second mode, as shown inFIG.12, when the temperature (T2) of the substrate25reaches the critical temperature (Af) by delivering the energy to the electrodes or the substrate25, a second circular loop of the substrate25may be formed, where the second diameter (R2) of the second circular loop may be smaller than the first diameter (R1). The shape-memory alloy of the substrate25may be pre-deformed such that the second diameter (R2) is slightly larger than the circumferential tissue and the electrodes23firmly contact the circumferential tissue in the second mode.

In embodiments, the substrate may be made of two-way shape memory alloy but may be made of three-way (or higher order) shape-memory alloy, depending on the application. For instance, the substrate may be made of three-way shape-memory alloy and pre-deformed so that the substrate has return to three shapes at three different temperatures.

The apparatus and methods described herein can be used to treat not only hypertension, but also other suitable types of diseases, such as chronic renal diseases, cardiovascular disorders, cardiac arrhythmias, and clinical syndromes where the renal afferent activation is involved. Using the catheter in embodiments, as compared to percutaneous catheter and surgical instrumentation, the physician may treat the diseases in an easier and safer manner.

In the description, numerous details are set forth for purposes of explanation in order to provide a thorough understanding of the present invention. However, it will be apparent to one skilled in the art that not all of these specific details are required in order to practice the present invention.

Additionally, while specific embodiments have been illustrated and described in this specification, those of ordinary skill in the art appreciate that any arrangement that is calculated to achieve the same purpose may be substituted for the specific embodiments disclosed. This disclosure is intended to cover any and all adaptations or variations of the present invention, and it is to be understood that the terms used in the following claims should not be construed to limit the invention to the specific embodiments disclosed in the specification. Rather, the scope of the invention is to be determined entirely by the following claims, which are to be construed in accordance with the established doctrines of claim interpretation, along with the full range of equivalents to which such claims are entitled.