BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to medical devices, systems, apparatus, and methods for modifying nerve function and treating disease. More particularly, the present invention relates to methods and apparatus for imaging and targeting peripheral nerves in tissue regions surrounding body lumens and cavities, including afferent and efferent nerves within the muscles layers, urothelium and submucosa surrounding the renal pelvis.

Thermally-induced renal neuromodulation via intravascular access is known and described, for example, in U.S. Patent Publication No. 2011/0060324. A catheter is inserted into a vessel in the leg and advanced into a renal artery where the catheter delivers RF energy to the vessel wall in order to damage or ablate the renal nerves. Recent studies have demonstrated that this procedure is not always effective. One reason for poor efficacy is that the nerves vary in location from patient to patient. Since the procedure is done under fluoroscopic imaging with systemic contrast, it is difficult or impossible for a practitioner to know where the nerves are located and to position the RF electrode(s) near the nerves.

An improved renal denervation protocol is described in U.S. Patent Publication No. 2013/0178824 which is commonly owned with the present application. A nerve ablation apparatus is introduced into the renal pelvis of a kidney to treat renal nerves embedded in tissue surrounding the renal pelvis. Access to the renal pelvis may be via the urinary tract or via minimally invasive incisions through the abdomen and kidney tissue. Treatment is effected by exchanging energy, typically delivering heat or extracting heat through a wall of the renal pelvis, or by delivering active substances. While an improvement over intravascular renal nerve denervation, denervation via the renal pelvis also suffers from lack of specificity for particular nerve structures.

Therefore, it would be advantageous to provide visualization of the afferent and efferent renal nerves during a renal denervation procedure to allow improved targeting of specific nerves for treatment. At least some of these objectives will be met by the inventions described below.

2. Description of the Background Art

U.S. Patent Publication Nos. 2011/0060324 and 2013/0178824 have been described above. Hsu et al. (2011) Curr Opin Urol 24:66-74 and Whitney et al. (2014) Nature Biotechnology 29: 352-356, describe fluorescently labeled peptides that preferentially bind to nerve tissue.

SUMMARY OF THE INVENTION

The present invention provides apparatus, systems, and methods for imaging and treating peripheral nerves in a patient. In exemplary embodiments, apparatus, systems, and methods are intended for disrupting, inhibiting, denervating and/or modulating the activity of targeted renal nerves which surround a patient's kidney by exchanging energy or delivering active agents or substances to the renal nerves which lie within the wall of the renal pelvis or adjacent to the renal pelvis within the kidney. Most commonly, such renal denervation and/or modulation will be for the purpose of reducing blood pressure in patients suffering from and/or diagnosed with hypertension, but the methods and apparatus of the present invention could be used for treating patients diagnosed with other conditions as described in U.S. Patent Publication No. 2013/0178824, the full disclosure of which is incorporated herein by reference. The energy exchange or agent delivery is effected through a wall of the renal pelvis, typically using an effector which has been positioned within the interior of the renal pelvis. In other embodiments, the targeted nerves can be treated using external energy sources, such as high intensity focused ultrasound (HIFU), as described in U.S. Pat. Nos. 8,715,209; 8,715,209; 8,622,937; 8,622,937; 8,622,937; 8,622,937; 8,556,834; 8,517,962; 8,517,962; 8,512,262; 8,469,904; 8,388,535; 8,374,674; 8,372,009; 8,295,912; 8,277,398; 8,167,805; and 8,137,274. The full disclosures of which are incorporated by reference.

The renal blood vessels, including the renal arteries and to a lesser extent the renal veins, enter the kidney in a branching network from the main renal artery and main renal vein leading to the kidney. The renal nerves are present in the adventitial tissue surrounding these branching blood vessels as well as in the tissue bed adjacent to the external wall of the renal pelvis. The renal nerves are also in the wall of the renal pelvis in the form of a dense nerve matrix consisting of both afferent and efferent nerves between the muscle layers as well as within the endothelium and submucosa. The present invention provides for enhanced imaging of renal peripheral nerves in tissue surrounding the kidneys and other tissue regions.

In a first aspect of the present invention, a method for targeted treatment of a peripheral nerve in a patient comprises providing a real-time fluorescent image of a tissue region where a target peripheral nerve has an enhanced appearance in the fluorescent image. A treatment element is advanced from an adjacent body lumen or cavity through the tissue region toward the peripheral nerve(s) while viewing the fluorescent image, and the peripheral nerve(s) is/are treated using the treatment element.

In exemplary embodiments, the fluorescent image is produced by injecting a fluorescent label which preferentially binds to nerve tissue within the tissue region and illuminating the tissue region with radiation at a wavelength which excites the fluorescent label. The fluorescent label may be injected systemically or, alternatively or additionally, may be injected locally into the tissue region.

The tissue region is illuminated using a radiation source having a fluorescent or other wavelength selected to excite the fluorescent label to emit a discernable signal, usually a fluorescent or visible light wavelength that can be detected fluoroscopically or optically. In exemplary embodiments, the illumination will be delivered by an endoscope located in the body lumen or cavity, such as a ureteroscope introduced into the renal pelvis of a kidney. In addition to delivering the illumination radiation, the tissue region may be imaged using the ureteroscope or other endoscope to produce the image. The use of optical fibers for delivering and receiving fluorescent and other radiation wavelengths is well known, as is the use of solid state emitters and receivers on endoscopes and similar tools. Any combination of known (or yet to be developed) radiation sources and detectors may be employed for delivery of excitation energy and detection of enhanced images in the methods and systems described below.

While the exemplary methods herein describe imaging using an endoscope, the methods and systems of the present invention may also image the tissue region using an external fluoroscope to produce the image. Similarly, while the exemplary methods herein describe imaging using the endoscope to deliver the treatment, the methods and systems of the present invention may also rely on delivering the treatment from an external source. When using an endoscope, a treatment element may advance from the endoscope. For example, the treatment element may comprise a needle, electrode or other tissue-penetrating element which is advanced into the tissue region. The treatment element will typically deliver energy through the treatment element into the tissue region, wherein the energy usually comprises radiofrequency energy. The treatment element could also be a needle which delivers an ablative solution to the target nerve.

In a second aspect of the present invention, a method for denervating nerves surrounding the renal pelvis comprises injecting a fluorescent label such that the fluorescent label preferentially binds to peripheral nerve tissue in a tissue region surrounding the renal pelvis. Images of the peripheral nerves in tissue region are enhanced by the label, and a treatment element is oriented toward one or more target peripheral nerves within the tissue region while viewing the enhanced images of the peripheral nerves. Target peripheral nerve(s) are treated using the treatment element.

The fluorescent label may be injected systemically or locally into the tissue region. The enhanced fluorescent image may be obtained by illuminating the tissue region with radiation at a wavelength which excites the fluorescent label. Typically, the tissue region is illuminated using a radiation source delivered by an endoscope located in the renal pelvis. The image of the tissue region may be obtained using the endoscope or by using an external fluoroscope to produce the image. Orienting the treatment element typically comprises advancing the treatment element from the endoscope, usually by penetrating the treatment element into the tissue region or placing it in contact or adjacent to the tissue. Treating usually comprises delivering energy through the treatment element into the tissue region, and the energy comprises radiofrequency energy. In alternative embodiments, orienting the treatment element may comprise aiming an external energy source to transcutaneously deliver energy to the target peripheral nerve where, for example, the external energy source may generate high intensity focused ultrasound (HIFU).

In addition to orienting the treatment element, the methods of the present invention may be used to determine the depth and/or size of the target peripheral nerves based on the image and to then calculate at least one of time, power level, temperature, waveform, and frequency need to effectively ablate the target nerves. For example, the imaging unit or a controller may be configured to analyze the size, brightness, and/or other image characteristics to determine the size, pattern and depth of the target nerves. Based on the size, pattern, and depth so determined, the time, intensity and other treatment parameters can be calculated, and energy delivery can be controlled and delivered automatically or delivered manually by the treating physician.

A system for targeted treatment of a peripheral nerve in a patient comprises an endoscopic imaging tool configured to produce a fluoroscopically enhanced image, a nerve treatment element or tool configured to be advanced under endoscopic guidance toward a target peripheral nerve which has been labeled with an injectable fluorescent label, and a controller configured to control the delivery of energy through the treatment element to ablate the target peripherals nerve. Either or both the endoscopic imaging tool and the treatment tool can be configured to be advanced from or through an adjacent body lumen or cavity, and the treatment tool can be further configured to be advanced to the tissue region toward the peripheral nerve while viewing the fluorescent image.

The systems may further comprise the injectable fluorescent label that preferentially binds to peripheral nerve tissue in a tissue region, such as tissue adjacent a renal pelvis. Typically, the controller will include a display for observing the image of the targeted peripheral nerve, and the controller is usually configured to adjust at least one of time, power level, temperature, waveform, and frequency to control the delivery of energy through the treatment element to ablate the target peripherals nerve.

Typically, the fluorescent molecule is excited to emit a certain visible light wavelength. Then the image can be seen directly using the excitation wavelength and white light. But some molecules fluoresce in non-visible wavelengths (e.g. infra-red IR or ultraviolet UV). If using such molecules, an IR or UV sensor/filter must be incorporated into the image acquisition and this must be displayed in visible format on a screen, preferably being overlaid onto the white-light image.

