Patent Publication Number: US-9848946-B2

Title: Self-expanding cooling electrode for renal nerve ablation

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 13/243,105, filed on Sep. 23, 2011, now U.S. Pat. No. 9,028,485, which claims the benefit of Provisional Patent Application Ser. Nos. 61/413,781 filed Nov. 15, 2010 and 61/491,730 filed May 31, 2011, to which priority is claimed pursuant to 35 U.S.C. §119(e) and the entirety of which are hereby incorporated herein by reference. 
    
    
     SUMMARY 
     Embodiments of the disclosure are directed to apparatuses and methods for ablating target tissue from within a vessel or other structure of the body. Embodiments of the disclosure are directed to apparatuses and methods for ablating perivascular renal nerves from within the renal artery for the treatment of hypertension. Embodiments of the disclosure include a self-expanding cooling electrode configured to deliver high frequency energy to innervated perivascular tissue adjacent a renal artery while providing protective cooling for the renal artery. Embodiments of a self-expanding cooling electrode include various tube arrangements constructed from metallic material that expands and contracts in response to changes in temperature, and that provide for concurrent self-expansion and protective cooling in response to a reduction in electrode temperature lower than a neutral temperature, such as an ambient temperature of the human body. 
     In accordance with various embodiments, an apparatus includes a metallic tube arrangement comprising an electrode region configured to expand radially and contract radially in response to increasing and decreasing a temperature at the electrode region, respectively. The electrode region is configured for intravascular deployment and delivery of high frequency energy to target tissue of a target vessel of the body. The electrode region is configured to expand radially to a diameter sufficient to contact an inner wall of the target vessel in response to a decrease in electrode region temperature and to contract radially to a diameter smaller than a diameter of the target vessel in response to an increase in electrode region temperature. 
     According to various embodiments, an apparatus includes a metallic tube arrangement comprising a proximal end, a distal end, an inlet, and an outlet. The distal end comprises a coil section and the proximal end comprises the inlet adapted to receive thermal transfer fluid. At least the coil section of the tube arrangement is dimensioned for deployment within a target vessel. The coil section is configured to expand radially to a diameter sufficient to contact an inner wall of the target vessel in response to receiving cooled thermal transfer fluid. At least a portion of the coil section defines an electrode configured to deliver high frequency energy to target tissue. The proximal end of the metallic tube arrangement is configured to electrically couple to an electrical energy generator. The coil section is configured to contract radially to a diameter smaller than an inner wall of the target vessel in response to removal of the cooled thermal transfer fluid via the outlet. 
     Various embodiments are directed to methods that involve supplying thermal transfer fluid to a metallic tube arrangement positioned within a target vessel of the body. The tube arrangement comprises a coiled section having a diameter that changes in response to changing a temperature of the thermal transfer fluid. Methods further involve increasing the diameter of the coiled section such that portions of the coiled section contact portions of the target vessel in response to decreasing the temperature of the thermal transfer fluid, delivering high frequency energy to the target vessel from one or more electrode portions of the tube arrangement while the coiled section portions are in contact with the target vessel portions, and decreasing the diameter of the coiled section to a diameter less than a diameter of the target vessel in response to increasing the temperature of the thermal transfer fluid. 
     These and other features can be understood in view of the following detailed discussion and the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is an illustration of a right kidney and renal vasculature including a renal artery branching laterally from the abdominal aorta; 
         FIGS. 2A and 2B  illustrate sympathetic innervation of the renal artery; 
         FIG. 3A  illustrates various tissue layers of the wall of the renal artery; 
         FIGS. 3B and 3C  illustrate a portion of a renal nerve; 
         FIG. 4  shows an expandable cooling electrode adapted for renal nerve ablation in a low-profile introduction configuration in accordance with various embodiments; 
         FIG. 5  shows an expandable cooling electrode adapted for renal nerve ablation in an ablation configuration in accordance with various embodiments; 
         FIGS. 6A through 6C  show various aspects of an ablation apparatus comprising an expandable cooling electrode extending from a distal end of a delivery sheath in accordance with various embodiments; 
         FIG. 7  shows a cross-section of a coiled section of an expandable cooling electrode having a thermal memory metallic tube construction in accordance with various embodiments; 
         FIG. 8  shows a cross-section of a coiled section of an expandable cooling electrode having a bi-metallic tube construction in accordance with various embodiments; 
         FIG. 9  shows a cross-section of a coiled section of an expandable cooling electrode having an asymmetric bi-layer tube construction in accordance with various embodiments; and 
         FIG. 10  shows a representative RF renal therapy apparatus in accordance with various embodiments. 
     
    
    
     DETAILED DESCRIPTION 
     Embodiments of the disclosure are directed to apparatuses and methods for improved vessel wall contact and control in ablation of target tissue, such as perivascular renal nerves for the control of hypertension. Embodiments of the disclosure are directed to various methods of ablating tissue at a short distance while protecting closer tissue. Embodiments of the disclosure are directed to methods of constructing a self-expanding tubular cooling RF electrode. 
     Maintaining good contact with a wall of the renal artery during ablation of perivascular renal nerves has been difficult. Conventional approaches often have problems in obtaining good contact between an intravascular ablation device and the artery wall, resulting in ineffective ablation of target nerves, or resulting in undesirable injury to arterial wall tissue. If contact is variable, the tissue temperatures are not well controlled, and an ablative temperature may not be achieved in the target tissue, while temperature in other areas, such as portions of the artery wall, may deviate enough to cause unwanted arterial tissue injury. For ideal anatomy, good vessel apposition can be achieved more easily, but especially with tortuous or diseased renal arteries, there can be very poor contact to effectively and predictably transfer heat, electrical current, or other energy from an ablation device to the target tissue. 
     Various embodiments are directed to ablation devices and methods that provide for improved vessel contact, as well as cooling the vessel at the line of contact, for reduced vessel injury. According to some embodiments, an ablation apparatus includes a metallic coiled structure which expands when it is cooled. The expanded coiled structure makes good contact with the vessel wall, and then portions of the coiled structure are used as RF electrodes to deliver energy to the nearby tissues. The coiled structure preferably includes a coiled metallic tube. Cooling fluid is passed through the coiled tube to concurrently cause coil expansion and to cool and protect the vessel wall. 
     The cooled coiled structure prevents thermal injury to the vessel where the coiled structure contacts the vessel wall, while RF energy delivered from the electrode(s) is propagated beyond the extent of the cooled region. As such, a single coiled structure can provide improved vessel contact, RF ablation of target tissue, and cooling for vessel wall protection simultaneously. 
     Thermal memory metal tubing, for example, can be used for the coiled structure. As the temperature is lowered or raised from a neutral temperature, the coiled structure loosens or tightens, and moves outward toward the vessel wall or inward away from the vessel wall, depending on the temperature. A cooled fluid can be passed through the coiled structure, causing the coiled structure of the electrode to expand outward toward the artery wall. The coiled structure can be adapted for phase-change cryothermal cooling by incorporating one or more orifices or narrowings to induce the phase change, or a simple cooled fluid can be used since the amount of tissue to be cooled is relatively small. 
     The side of the coiled structure oriented away from the artery wall can be insulated to reduce heat transfer from the blood, so that local vessel wall cooling and protection is more effective. When cooling of the coiled structure is terminated, the coiled structure deforms away from the vessel wall, to form a lower profile for introduction or removal of the device to and from the lumen of a target vessel. After delivering the device into the lumen of the target vessel, the coiled structure automatically self-deploys to achieve good vessel wall contact in response to cooling. After completion of an ablation procedure, the coiled structure of the electrode returns to a low profile configuration when the cooling is terminated. 
     A return tube can be included in the construction of the coiled electrode structure for handling spent cooling fluid. The return tube can be a parallel coil, or a straight tube extending through the center of the coiled structure, or other shape. A positioning sheath is preferably provided for introduction and advancement of the coiled structure within the vasculature. The self-expanding coiled structure is coupled to an external control system which provides cooling fluid and RF energy to the coiled structure. 
     According to various embodiments, an expandable cooling structure which incorporates a thermally activated RF electrode is constructed as an elongated tube having a length sufficient to extend between a patient&#39;s renal artery and a percutaneous access location of the patient&#39;s body. Most of the elongated tube is preferably insulated and used to conduct RF energy and cooling fluid to an expandable cooling electrode provided at the distal end of the elongated tube. Exposed portions of the coiled structure act as an RF electrode(s) to deliver energy to innervated perivascular renal tissue. The cooled coiled structure prevents thermal injury to the renal artery where the coiled structure contacts the renal artery wall, while the RF energy is delivered farther from the electrode(s) than the extent of the cooled region. 
     The coiled structure is preferably delivered into the lumen of the renal artery using a delivery sheath from an aortal access location. The sheath can either be retracted from the coiled structure or the coiled structure can be advanced out of the sheath&#39;s distal tip. The coiled structure can be in direct contact with the artery wall, rather than contained within a catheter balloon as in prior cryothermal approaches. This arrangement provides for improved wall contact for both cooling and RF ablation, and does not block blood flow within the renal artery. This allows the heating and cooling to be activated simultaneously and for an extended duration treatment if required. Using the various thermal shape-change structures disclosed herein, as the temperature is lowered or raised from a neutral temperature, the coiled structure loosens or tightens, and moves outward toward the artery wall or inward away from the artery wall, depending on the temperature. 
     Various embodiments of the disclosure are directed to apparatuses and methods for renal denervation for treating hypertension. Hypertension is a chronic medical condition in which the blood pressure is elevated. Persistent hypertension is a significant risk factor associated with a variety of adverse medical conditions, including heart attacks, heart failure, arterial aneurysms, and strokes. Persistent hypertension is a leading cause of chronic renal failure. Hyperactivity of the sympathetic nervous system serving the kidneys is associated with hypertension and its progression. Deactivation of nerves in the kidneys via renal denervation can reduce blood pressure, and may be a viable treatment option for many patients with hypertension who do not respond to conventional drugs. 
     The kidneys are instrumental in a number of body processes, including blood filtration, regulation of fluid balance, blood pressure control, electrolyte balance, and hormone production. One primary function of the kidneys is to remove toxins, mineral salts, and water from the blood to form urine. The kidneys receive about 20-25% of cardiac output through the renal arteries that branch left and right from the abdominal aorta, entering each kidney at the concave surface of the kidneys, the renal hilum. 
     Blood flows into the kidneys through the renal artery and the afferent arteriole, entering the filtration portion of the kidney, the renal corpuscle. The renal corpuscle is composed of the glomerulus, a thicket of capillaries, surrounded by a fluid-filled, cup-like sac called Bowman&#39;s capsule. Solutes in the blood are filtered through the very thin capillary walls of the glomerulus due to the pressure gradient that exists between the blood in the capillaries and the fluid in the Bowman&#39;s capsule. The pressure gradient is controlled by the contraction or dilation of the arterioles. After filtration occurs, the filtered blood moves through the efferent arteriole and the peritubular capillaries, converging in the interlobular veins, and finally exiting the kidney through the renal vein. 
     Particles and fluid filtered from the blood move from the Bowman&#39;s capsule through a number of tubules to a collecting duct. Urine is formed in the collecting duct and then exits through the ureter and bladder. The tubules are surrounded by the peritubular capillaries (containing the filtered blood). As the filtrate moves through the tubules and toward the collecting duct, nutrients, water, and electrolytes, such as sodium and chloride, are reabsorbed into the blood. 
     The kidneys are innervated by the renal plexus which emanates primarily from the aorticorenal ganglion. Renal ganglia are formed by the nerves of the renal plexus as the nerves follow along the course of the renal artery and into the kidney. The renal nerves are part of the autonomic nervous system which includes sympathetic and parasympathetic components. The sympathetic nervous system is known to be the system that provides the bodies “fight or flight” response, whereas the parasympathetic nervous system provides the “rest and digest” response. Stimulation of sympathetic nerve activity triggers the sympathetic response which causes the kidneys to increase production of hormones that increase vasoconstriction and fluid retention. This process is referred to as the renin-angiotensin-aldosterone-system (RAAS) response to increased renal sympathetic nerve activity. 
     In response to a reduction in blood volume, the kidneys secrete renin, which stimulates the production of angiotensin. Angiotensin causes blood vessels to constrict, resulting in increased blood pressure, and also stimulates the secretion of the hormone aldosterone from the adrenal cortex. Aldosterone causes the tubules of the kidneys to increase the reabsorption of sodium and water, which increases the volume of fluid in the body and blood pressure. 
     Congestive heart failure (CHF) is a condition that has been linked to kidney function. CHF occurs when the heart is unable to pump blood effectively throughout the body. When blood flow drops, renal function degrades because of insufficient perfusion of the blood within the renal corpuscles. The decreased blood flow to the kidneys triggers an increase in sympathetic nervous system activity (i.e., the RAAS becomes too active) that causes the kidneys to secrete hormones that increase fluid retention and vasorestriction. Fluid retention and vasorestriction in turn increases the peripheral resistance of the circulatory system, placing an even greater load on the heart, which diminishes blood flow further. If the deterioration in cardiac and renal functioning continues, eventually the body becomes overwhelmed, and an episode of heart failure decompensation occurs, often leading to hospitalization of the patient. 
       FIG. 1  is an illustration of a right kidney  10  and renal vasculature including a renal artery  12  branching laterally from the abdominal aorta  20 . In  FIG. 1 , only the right kidney  10  is shown for purposes of simplicity of explanation, but reference will be made herein to both right and left kidneys and associated renal vasculature and nervous system structures, all of which are contemplated within the context of embodiments of the disclosure. The renal artery  12  is purposefully shown to be disproportionately larger than the right kidney  10  and abdominal aorta  20  in order to facilitate discussion of various features and embodiments of the present disclosure. 
     The right and left kidneys are supplied with blood from the right and left renal arteries that branch from respective right and left lateral surfaces of the abdominal aorta  20 . Each of the right and left renal arteries is directed across the crus of the diaphragm, so as to form nearly a right angle with the abdominal aorta  20 . The right and left renal arteries extend generally from the abdominal aorta  20  to respective renal sinuses proximate the hilum  17  of the kidneys, and branch into segmental arteries and then interlobular arteries within the kidney  10 . The interlobular arteries radiate outward, penetrating the renal capsule and extending through the renal columns between the renal pyramids. Typically, the kidneys receive about 20% of total cardiac output which, for normal persons, represents about 1200 mL of blood flow through the kidneys per minute. 
     The primary function of the kidneys is to maintain water and electrolyte balance for the body by controlling the production and concentration of urine. In producing urine, the kidneys excrete wastes such as urea and ammonium. The kidneys also control reabsorption of glucose and amino acids, and are important in the production of hormones including vitamin D, renin and erythropoietin. 
     An important secondary function of the kidneys is to control metabolic homeostasis of the body. Controlling hemostatic functions include regulating electrolytes, acid-base balance, and blood pressure. For example, the kidneys are responsible for regulating blood volume and pressure by adjusting volume of water lost in the urine and releasing erythropoietin and renin, for example. The kidneys also regulate plasma ion concentrations (e.g., sodium, potassium, chloride ions, and calcium ion levels) by controlling the quantities lost in the urine and the synthesis of calcitrol. Other hemostatic functions controlled by the kidneys include stabilizing blood pH by controlling loss of hydrogen and bicarbonate ions in the urine, conserving valuable nutrients by preventing their excretion, and assisting the liver with detoxification. 
     Also shown in  FIG. 1  is the right suprarenal gland  11 , commonly referred to as the right adrenal gland. The suprarenal gland  11  is a star-shaped endocrine gland that rests on top of the kidney  10 . The primary function of the suprarenal glands (left and right) is to regulate the stress response of the body through the synthesis of corticosteroids and catecholamines, including cortisol and adrenaline (epinephrine), respectively. Encompassing the kidneys  10 , suprarenal glands  11 , renal vessels  12 , and adjacent perirenal fat is the renal fascia, e.g., Gerota&#39;s fascia, (not shown), which is a fascial pouch derived from extraperitoneal connective tissue. 
     The autonomic nervous system of the body controls involuntary actions of the smooth muscles in blood vessels, the digestive system, heart, and glands. The autonomic nervous system is divided into the sympathetic nervous system and the parasympathetic nervous system. In general terms, the parasympathetic nervous system prepares the body for rest by lowering heart rate, lowering blood pressure, and stimulating digestion. The sympathetic nervous system effectuates the body&#39;s fight-or-flight response by increasing heart rate, increasing blood pressure, and increasing metabolism. 
     In the autonomic nervous system, fibers originating from the central nervous system and extending to the various ganglia are referred to as preganglionic fibers, while those extending from the ganglia to the effector organ are referred to as postganglionic fibers. Activation of the sympathetic nervous system is effected through the release of adrenaline (epinephrine) and to a lesser extent norepinephrine from the suprarenal glands  11 . This release of adrenaline is triggered by the neurotransmitter acetylcholine released from preganglionic sympathetic nerves. 
     The kidneys and ureters (not shown) are innervated by the renal nerves  14 .  FIGS. 1 and 2A-2B  illustrate sympathetic innervation of the renal vasculature, primarily innervation of the renal artery  12 . The primary functions of sympathetic innervation of the renal vasculature include regulation of renal blood flow and pressure, stimulation of renin release, and direct stimulation of water and sodium ion reabsorption. 
     Most of the nerves innervating the renal vasculature are sympathetic postganglionic fibers arising from the superior mesenteric ganglion  26 . The renal nerves  14  extend generally axially along the renal arteries  12 , enter the kidneys  10  at the hilum  17 , follow the branches of the renal arteries  12  within the kidney  10 , and extend to individual nephrons. Other renal ganglia, such as the renal ganglia  24 , superior mesenteric ganglion  26 , the left and right aorticorenal ganglia  22 , and celiac ganglia  28  also innervate the renal vasculature. The celiac ganglion  28  is joined by the greater thoracic splanchnic nerve (greater TSN). The aorticorenal ganglia  26  is joined by the lesser thoracic splanchnic nerve (lesser TSN) and innervates the greater part of the renal plexus. 
     Sympathetic signals to the kidney  10  are communicated via innervated renal vasculature that originates primarily at spinal segments T 10 -T 12  and L 1 . Parasympathetic signals originate primarily at spinal segments S 2 -S 4  and from the medulla oblongata of the lower brain. Sympathetic nerve traffic travels through the sympathetic trunk ganglia, where some may synapse, while others synapse at the aorticorenal ganglion  22  (via the lesser thoracic splanchnic nerve, i.e., lesser TSN) and the renal ganglion  24  (via the least thoracic splanchnic nerve, i.e., least TSN). The postsynaptic sympathetic signals then travel along nerves  14  of the renal artery  12  to the kidney  10 . Presynaptic parasympathetic signals travel to sites near the kidney  10  before they synapse on or near the kidney  10 . 
     With particular reference to  FIG. 2A , the renal artery  12 , as with most arteries and arterioles, is lined with smooth muscle  34  that controls the diameter of the renal artery lumen  13 . Smooth muscle, in general, is an involuntary non-striated muscle found within the media layer of large and small arteries and veins, as well as various organs. The glomeruli of the kidneys, for example, contain a smooth muscle-like cell called the mesangial cell. Smooth muscle is fundamentally different from skeletal muscle and cardiac muscle in terms of structure, function, excitation-contraction coupling, and mechanism of contraction. 
     Smooth muscle cells can be stimulated to contract or relax by the autonomic nervous system, but can also react on stimuli from neighboring cells and in response to hormones and blood borne electrolytes and agents (e.g., vasodilators or vasoconstrictors). Specialized smooth muscle cells within the afferent arteriole of the juxtaglomerular apparatus of kidney  10 , for example, produces renin which activates the angiotension II system. 
     The renal nerves  14  innervate the smooth muscle  34  of the renal artery wall  15  and extend lengthwise in a generally axial or longitudinal manner along the renal artery wall  15 . The smooth muscle  34  surrounds the renal artery circumferentially, and extends lengthwise in a direction generally transverse to the longitudinal orientation of the renal nerves  14 , as is depicted in  FIG. 2B . 
     The smooth muscle  34  of the renal artery  12  is under involuntary control of the autonomic nervous system. An increase in sympathetic activity, for example, tends to contract the smooth muscle  34 , which reduces the diameter of the renal artery lumen  13  and decreases blood perfusion. A decrease in sympathetic activity tends to cause the smooth muscle  34  to relax, resulting in vessel dilation and an increase in the renal artery lumen diameter and blood perfusion. Conversely, increased parasympathetic activity tends to relax the smooth muscle  34 , while decreased parasympathetic activity tends to cause smooth muscle contraction. 
       FIG. 3A  shows a segment of a longitudinal cross-section through a renal artery, and illustrates various tissue layers of the wall  15  of the renal artery  12 . The innermost layer of the renal artery  12  is the endothelium  30 , which is the innermost layer of the intima  32  and is supported by an internal elastic membrane. The endothelium  30  is a single layer of cells that contacts the blood flowing though the vessel lumen  13 . Endothelium cells are typically polygonal, oval, or fusiform, and have very distinct round or oval nuclei. Cells of the endothelium  30  are involved in several vascular functions, including control of blood pressure by way of vasoconstriction and vasodilation, blood clotting, and acting as a barrier layer between contents within the lumen  13  and surrounding tissue, such as the membrane of the intima  32  separating the intima  32  from the media  34 , and the adventitia  36 . The membrane or maceration of the intima  32  is a fine, transparent, colorless structure which is highly elastic, and commonly has a longitudinal corrugated pattern. 
     Adjacent the intima  32  is the media  33 , which is the middle layer of the renal artery  12 . The media is made up of smooth muscle  34  and elastic tissue. The media  33  can be readily identified by its color and by the transverse arrangement of its fibers. More particularly, the media  33  consists principally of bundles of smooth muscle fibers  34  arranged in a thin plate-like manner or lamellae and disposed circularly around the arterial wall  15 . The outermost layer of the renal artery wall  15  is the adventitia  36 , which is made up of connective tissue. The adventitia  36  includes fibroblast cells  38  that play an important role in wound healing. 
     A perivascular region  37  is shown adjacent and peripheral to the adventitia  36  of the renal artery wall  15 . A renal nerve  14  is shown proximate the adventitia  36  and passing through a portion of the perivascular region  37 . The renal nerve  14  is shown extending substantially longitudinally along the outer wall  15  of the renal artery  12 . The main trunk of the renal nerves  14  generally lies in or on the adventitia  36  of the renal artery  12 , often passing through the perivascular region  37 , with certain branches coursing into the media  33  to enervate the renal artery smooth muscle  34 . 
     Embodiments of the disclosure may be implemented to provide varying degrees of denervation therapy to innervated renal vasculature. For example, embodiments of the disclosure may provide for control of the extent and relative permanency of renal nerve impulse transmission interruption achieved by denervation therapy delivered using a treatment apparatus of the disclosure. The extent and relative permanency of renal nerve injury may be tailored to achieve a desired reduction in sympathetic nerve activity (including a partial or complete block) and to achieve a desired degree of permanency (including temporary or irreversible injury). 
     Returning to  FIGS. 3B and 3C , the portion of the renal nerve  14  shown in  FIGS. 3B and 3C  includes bundles  14   a  of nerve fibers  14   b  each comprising axons or dendrites that originate or terminate on cell bodies or neurons located in ganglia or on the spinal cord, or in the brain. Supporting tissue structures  14   c  of the nerve  14  include the endoneurium (surrounding nerve axon fibers), perineurium (surrounds fiber groups to form a fascicle), and epineurium (binds fascicles into nerves), which serve to separate and support nerve fibers  14   b  and bundles  14   a . In particular, the endoneurium, also referred to as the endoneurium tube or tubule, is a layer of delicate connective tissue that encloses the myelin sheath of a nerve fiber  14   b  within a fasciculus. 
     Major components of a neuron include the soma, which is the central part of the neuron that includes the nucleus, cellular extensions called dendrites, and axons, which are cable-like projections that carry nerve signals. The axon terminal contains synapses, which are specialized structures where neurotransmitter chemicals are released in order to communicate with target tissues. The axons of many neurons of the peripheral nervous system are sheathed in myelin, which is formed by a type of glial cell known as Schwann cells. The myelinating Schwann cells are wrapped around the axon, leaving the axolemma relatively uncovered at regularly spaced nodes, called nodes of Ranvier. Myelination of axons enables an especially rapid mode of electrical impulse propagation called saltation. 
     In some embodiments, a treatment apparatus of the disclosure may be implemented to deliver denervation therapy that causes transient and reversible injury to renal nerve fibers  14   b . In other embodiments, a treatment apparatus of the disclosure may be implemented to deliver denervation therapy that causes more severe injury to renal nerve fibers  14   b , which may be reversible if the therapy is terminated in a timely manner. In preferred embodiments, a treatment apparatus of the disclosure may be implemented to deliver denervation therapy that causes severe and irreversible injury to renal nerve fibers  14   b , resulting in permanent cessation of renal sympathetic nerve activity. For example, a treatment apparatus may be implemented to deliver a denervation therapy that disrupts nerve fiber morphology to a degree sufficient to physically separate the endoneurium tube of the nerve fiber  14   b , which can prevent regeneration and re-innervation processes. 
     By way of example, and in accordance with Seddon&#39;s classification as is known in the art, a treatment apparatus of the disclosure may be implemented to deliver a denervation therapy that interrupts conduction of nerve impulses along the renal nerve fibers  14   b  by imparting damage to the renal nerve fibers  14   b  consistent with neruapraxia. Neurapraxia describes nerve damage in which there is no disruption of the nerve fiber  14   b  or its sheath. In this case, there is an interruption in conduction of the nerve impulse down the nerve fiber, with recovery taking place within hours to months without true regeneration, as Wallerian degeneration does not occur. Wallerian degeneration refers to a process in which the part of the axon separated from the neuron&#39;s cell nucleus degenerates. This process is also known as anterograde degeneration. Neurapraxia is the mildest form of nerve injury that may be imparted to renal nerve fibers  14   b  by use of a treatment apparatus according to embodiments of the disclosure. 
     A treatment apparatus may be implemented to interrupt conduction of nerve impulses along the renal nerve fibers  14   b  by imparting damage to the renal nerve fibers consistent with axonotmesis. Axonotmesis involves loss of the relative continuity of the axon of a nerve fiber and its covering of myelin, but preservation of the connective tissue framework of the nerve fiber. In this case, the encapsulating support tissue  14   c  of the nerve fiber  14   b  are preserved. Because axonal continuity is lost, Wallerian degeneration occurs. Recovery from axonotmesis occurs only through regeneration of the axons, a process requiring time on the order of several weeks or months. Electrically, the nerve fiber  14   b  shows rapid and complete degeneration. Regeneration and re-innervation may occur as long as the endoneural tubes are intact. 
     A treatment apparatus may be implemented to interrupt conduction of nerve impulses along the renal nerve fibers  14   b  by imparting damage to the renal nerve fibers  14   b  consistent with neurotmesis. Neurotmesis, according to Seddon&#39;s classification, is the most serious nerve injury in the scheme. In this type of injury, both the nerve fiber  14   b  and the nerve sheath are disrupted. While partial recovery may occur, complete recovery is not possible. Neurotmesis involves loss of continuity of the axon and the encapsulating connective tissue  14   c , resulting in a complete loss of autonomic function, in the case of renal nerve fibers  14   b . If the nerve fiber  14   b  has been completely divided, axonal regeneration causes a neuroma to form in the proximal stump. 
     A more stratified classification of neurotmesis nerve damage may be found by reference to the Sunderland System as is known in the art. The Sunderland System defines five degrees of nerve damage, the first two of which correspond closely with neurapraxia and axonotmesis of Seddon&#39;s classification. The latter three Sunderland System classifications describe different levels of neurotmesis nerve damage. 
     The first and second degrees of nerve injury in the Sunderland system are analogous to Seddon&#39;s neurapraxia and axonotmesis, respectively. Third degree nerve injury, according to the Sunderland System, involves disruption of the endoneurium, with the epineurium and perineurium remaining intact. Recovery may range from poor to complete depending on the degree of intrafascicular fibrosis. A fourth degree nerve injury involves interruption of all neural and supporting elements, with the epineurium remaining intact. The nerve is usually enlarged. Fifth degree nerve injury involves complete transection of the nerve fiber  14   b  with loss of continuity. 
     Turning now to  FIGS. 4 and 5 , there is illustrated a self-expanding cooling electrode  100  adapted for renal nerve ablation in accordance with various embodiments.  FIG. 4  shows an expandable cooling electrode  100  in a low-profile introduction configuration. When in the low-profile introduction configuration, the expandable cooling electrode  100  can be deployed within the lumen of a target vessel, such as a patient&#39;s renal artery, or other structure of the body.  FIG. 5  shows the cooling electrode  100  in an expanded ablation configuration. When in the ablation configuration, the expandable cooling electrode  100  is preferably used to deliver high frequency energy (e.g., RF current) to target tissue of the vessel or other body tissue of interest. 
     According to various embodiments, and as shown in  FIG. 4 , an expandable cooling electrode  100  is constructed as a metallic tube  101  having a proximal and  102 , a distal end  104 , and a coil section  106  defined between the proximal and distal ends  102  and  104 . The metallic tube  101  is shown having a generally elongated configuration with a portion of the metallic tube  101  wrapped around itself to form the coiled section  106 . At the proximal end  102 , an inlet  110  and an outlet  112  of the metallic tube  101  are aligned in a co-parallel relationship. As such, access to both the inlet  110  and the outlet  112  of the metallic tube  101  are accessible from the proximal end  102 . 
     It is understood that the metallic tube  101  can be formed to assume a variety of configurations, and that those configurations shown in the drawings represent non-limiting examples of various embodiments. For example, the expandable cooling electrode  100  is shown in  FIGS. 4 and 5  to include a supply tube  111  and a return tube  113 . As illustrated, the distal end of the supply tube  111  includes the coiled section  106  wrapped around the return tube  113  which is shown to be a straight tube extending through the center of the coiled section  106 . In some embodiments, the return tube  113  can be shaped to include a coiled section aligned in a co-parallel relationship with the coiled section  106  of the supply tube  111 . In other embodiments, the return tube  113  need not be co-parallel with the supply tube  111  nor extend to the proximal end  102 . For example, the outlet  112  can be located anywhere distal of the coiled section  106 , such as at a location suited for expelling spent biocompatible thermal transfer fluid from the metallic tube  101  and into blood flowing past the metallic tube. 
     The supply and return tubes  111  and  113  include lumens through which a thermal transfer fluid can be transported. The materials used to fabricate the coiled section  106  of the metallic tube  101  allow the diameter of the coiled section  106  to change in response to changes in temperature. In preferred embodiments, the diameter of the coiled section  106  increases in response to cooling relative to ambient or a neutral temperature (e.g., body temperature), and decreases in response to warming relative to ambient or a neutral temperature. For example, as the temperature of the coiled section  106  is lowered or raised relative to a neutral temperature, the coiled section  106  loosens or tightens, and moves outwardly toward the vessel wall or inwardly away from the vessel wall, depending on the temperature. 
     According to various embodiments, the coiled section  106  of the metallic tube  101  can be formed from thermal memory metal tubing, bi-metallic tubing, bi-layer tubing, or other metallic tubing that undergoes a shape change in response to changes in temperature. Metallic materials used to form the coiled section  106  preferably have a negative thermal coefficient of expansion. More preferably, suitable metallic materials that can be used to construct the coiled section  106  includes those that have a linear negative thermal coefficient of expansion, in which the material&#39;s linear dimension changes as a function of temperature change (e.g., the fractional change in length per degree of temperature change). Portions of the metallic tube  101  proximal and distal to the coiled section  106  are preferably formed from metal or metal alloys that negligibly change shape in response to changes in temperature. 
     In the introduction configuration shown in  FIG. 4 , the coiled section  106  of the metallic tube  101  has a diameter of D 1 . The introduction diameter, D 1 , is preferably selected so that the expandable cooling electrode  100  can be readily and safely deployed in the lumen of a target vessel of the body, such as a renal artery. By way of example, and in the context of renal nerve ablation, the coiled section  106  may have an introduction diameter, D 1 , of about 1 mm to about 2.5 mm. In the ablation configuration shown in  FIG. 5 , the coiled section  106  of the metallic tube  101  has a diameter of D 2 . The expanded diameter, D 2 , is preferably selected so that the coiled section  106  makes contact with an inner wall of the target vessel. In the context of renal nerve ablation, for example, the coiled section  106  may have an expanded diameter, D 2 , of about 4 mm to about 8 mm. In various applications, the diameter of the coiled section  106  in its ablation configuration can increase between about 200% and about 800% relative to its introduction configuration. 
     Desired thermal response characteristics of the coiled section  106 , such as the degree and/or timeliness of expansion and contraction, can be designed into the coiled section  106  depending on application particulars and the type of thermal transfer fluid used to cool the coiled section  106 . A variety of thermal transfer fluids may be employed, including cold saline or cold saline and ethanol mixture, Freon or other fluorocarbon refrigerants, nitrous oxide, liquid nitrogen, and liquid carbon dioxide, for example. In some embodiments, a cooled thermal transfer fluid may be supplied by an external fluid source, circulated through the coiled section  106 , and spent thermal transfer fluid returned to the external fluid source. In other embodiments, a cooled biocompatible thermal transfer fluid may be supplied by an external fluid source, circulated through the coiled section  106 , and expelled into blood flowing through a target vessel, such as a renal artery. 
     According to some embodiments, the metallic tube  101  can be constructed to provide phase-change cryothermal cooling by incorporating one or more orifices or narrowings to induce the phase change at the coiled section  106 . A liquid cryogen, for example, can be supplied to the metallic tube  101  through inlet  110 . When released inside the coiled section  106 , the liquid cryogen undergoes a phase change that cools the coiled section  106  by absorbing the latent heat of vaporization from the surrounding tissue, and by cooling of the vaporized gas as it enters a region of lower pressure inside the coiled section  106  (via the Joule-Thomson effect). The gas released inside the distal portion of the coiled section  106  is exhausted through outlet  112 . The pressure inside the coiled section  106  may be controlled by regulating one or both of a rate at which cryogen is delivered and a rate at which the exhaust gas is extracted. 
     One or more temperature sensors may be provided at the coiled section  106  for measuring tube and/or arterial tissue temperature. One or more conductors can be used for coupling each of the temperature sensors to an external temperature unit. 
     A desired degree of shape change of the coiled section  106  can be achieved using different construction techniques and materials. The extent of shape change of the coiled section  106  can be induced over different temperature ranges, such as a relatively small temperature range or a relatively large temperature range. The change in shape of the coiled section  106  may be uniform or asymmetric depending on the construction of the coiled section  106 . Other properties and characteristics can be designed into the metallic tube  101  and coiled section  106 , such as flexibility, depending on the particular target vessel or other target structures of the body. 
     According to various embodiments, at least the coiled section  106  of the metallic tube  101  defines an electrode adapted to ablate target tissue of a target vessel, such as innervated perivascular tissue surrounding a patient&#39;s renal artery. All or a portion of the metallic tube  101 , such as the coiled section  106 , is preferably left exposed so that the exposed portion or portions of the metallic tube  101  define an ablation electrode, which electrically cooperates with another electrode during ablation. In some embodiments, the other electrode comprises an external pad electrode of an external generator, such as an RF generator. In such embodiments, the exposed portion(s) of the metallic tube  101  and the external electrode are operated in a monopolar configuration. According to other embodiments, the other electrode can be placed within the body in proximity to the exposed portion of the metallic tube  101 . For example, the other electrode can be placed within a renal vein in proximity to the renal artery in which the expandable cooling electrode  100  is situated. 
     The helical shape of the expandable cooling electrode  100  allows a spiral region of perivascular renal nerve tissue to be ablated to achieve termination of renal sympathetic nerve activity in a reduced amount of time relative to conventional approaches and with minimal or no injury to the renal artery. The expandable cooling electrode  100  advantageously provides for delivery of high frequency energy for ablating perivascular renal nerve tissue and simultaneous cooling to prevent thermal damage to the renal artery wall. The thermal mechanism used to cause expansion of the coiled section  106  of the expandable cooling electrode  100  also provides protective cooling for the renal artery wall. For example, the expandable cooling electrode  100  can be deployed within the lumen of a renal artery in its introduction configuration, cooled to cause expansion of the coiled section  106  to its ablation configuration, and energized to ablate at least a 360° spiral of innervated perivascular renal tissue without having to reposition the electrode  100  during the ablation procedure and without thermally injuring the renal artery wall. 
       FIGS. 6A through 6C  show various aspects of an ablation apparatus in accordance with various embodiments.  FIGS. 6A-6C  show an ablation catheter  105  comprising a sheath  90  and an expandable cooling electrode  100  extending from a distal end of the sheath  90 . The sheath  90  is shown to extend into the ostium of the renal artery  12  accessed from the aorta  20  inferior to the renal artery  12 . The sheath  90  includes a lumen  92  dimensioned to receive the expandable cooling electrode arrangement in its introduction configuration. The sheath  90  typically has a length sufficient to access a target vessel, such as the renal artery  12 , from a perivascular access location of the patient. 
     The expandable cooling electrode  100  is shown coupled to a tube arrangement  103  which includes supply and return tubes  111  and  113  that respectively extend along the length of the sheath  90 . The distal ends of supply and return tubes  111  and  113  are fluidly coupled to inlet  110  and outlet  112  of the metallic tube  101 , respectively. The proximal ends of the supply and return tubes  111  and  113  are preferably configured to fluidly coupled to supply and return couplings of an external thermal transfer fluid source. The proximal ends of the supply and return tubes  111  and  113  are electrically coupled to an external energy source, such as an RF generator. In order to electrically insulate the proximal ends of the supply and return tubes  111  and  113  from the external thermal transfer fluid source, non-metallic fluid couplings are preferably used to fluidly coupled the proximal ends of the supply and return tubes  111  and  113  to supply and return lines of the external thermal transfer fluid source. 
     The supply and return tubes  111  and  113  are preferably covered with insulation to electrically and thermally isolate the two tubes  111  and  113  from each other. The inner lumen  92  of the sheath  90  may also include insulation to prevent cooled thermal transfer fluid transported through the supply tube  111  from warming due to ambient heat produced by the body. In some embodiments, a low-conductivity fluid is used to limit undesired electrical pathways. 
     According to other embodiments, the supply and return tubes  111   113  need not be metallic. Electrically non-conductive supply and return tubes  111  and  113  can be fluidly coupled to inlet  110  and outlet  112  of the metallic tube  101 . According to such embodiments, an electrical conductor extends along the length of the sheath  102  and electrically couples the metallic tube  101  at its proximal end  102  with an external energy source. The electrical conductor can be supported on or encompassed within a lumen of the non-conductive supply tube  111  or return tube  113 . 
       FIG. 7  shows a cross-section of the coiled section  106  of the metallic tube  101  having a thermal memory metallic tube construction in accordance with various embodiments. In the embodiment shown in  FIG. 7 , the coiled section  106  is formed from a thermal memory metallic tube  122  having a lumen  123  through which thermal transfer fluid can be transported. The thermal memory metallic material used to form tube  122  of the coiled section  106  typically provides shape change over a relatively small temperature range. For example, suitable thermal memory metallic materials that provides for shape change over a relatively small temperature range include some alloys of nickel-titanium (nitinol), copper-zinc-aluminum-nickel, copper-aluminum-nickel, and some alloys of zinc, copper, gold and iron. These and other suitable thermal memory metallic materials can provide shape change over a temperature range of about 5° C., with transition chosen in the temperature range of about −10° C. to about +30° C. for this application, with about a 10° C. temperature hysteresis. 
       FIG. 7  further shows insulation  124  covering an outer region of the metallic tube  122  which is exposed to blood flowing in the target vessel. The insulation  124 , which is an optional feature, thermally insulates the side of the coiled section  106  oriented away from the vessel wall in order to reduce heat transfer from blood, so that local vessel wall cooling and protection is enhanced. 
       FIG. 8  shows a cross-section of the coiled section  106  of the metallic tube  101  having a bi-metallic tube construction in accordance with various embodiments. The embodiment shown in  FIG. 8  includes a metallic tube  101  constructed as a two-sided bi-metallic tube  101 . The bi-metallic tube  126  of the coiled section  106  is preferably formed by incorporating two metals  126   a  and  126   b  having differing thermal expansion properties. According to some embodiments, a first metal  126   a  is used to form half of the circumference of the bi-metallic tube  101 , and a second metal  126   b  is used to form the other half of the circumference of the bi-metallic tube  101 . The first and second metals  126   a  and  126   b  have differing thermal expansion properties. The two halves are welded or otherwise bonded to one another to form the bi-metallic tube structure  126  of the coiled section  106 . The bi-metallic tube  126  may include insulation  124  to thermally insulate the side of the coiled section  106  oriented away from the vessel wall for reasons previously discussed. 
     Use of bi-metallic tubing  126  in the construction of the coiled section  106  provides for a shape change of the coiled section  106  over a relatively large temperature range as compared to the thermal memory metallic material used to form tube  122  in the embodiment shown in  FIG. 7 . For example, suitable metals having differing thermal expansion properties that can be used to fabricate the bi-metallic tube  126  of the coiled section  106  include stainless steel and copper. These and other suitable bi-metallic metals can provide a gradual shape change over a several hundred degree temperature range, but the coiled section  106  can be designed to achieve the desired shape change resulting from temperature changes of about 10° C. to about 30° C. The practical temperature range is to stay above cryothermal injury temperatures, (about −10° C. or so) and below body temperature (about 37° C. or so). A smaller temperature range can be used so that the cooling required for actuating the coil is more easily achieved. 
     According to some embodiments, and depending on particulars of a specific application, an intravascular device of the type described above (and elsewhere) can be fabricated using metal tubing having an inner diameter that ranges between about 0.003″ and 0.012″, and outer diameter that ranges between about 0.006″ and 0.018″, and a wall thickness that ranges between about 0.0015″ and 0.005″. 
     In accordance with various embodiments, a polymer element or tube may be used in combination with a metal tube or a polymer element in the construction of the coiled section  106  (and other sections if desired). In some embodiments, the coiled section  106  is constructed using a polymer tube and a metal tube or element. In other embodiments, the coiled section  106  excludes a metal tube or element, and uses a combination of a polymeric tube and a polymer element. For example, a polymer tube may be used with an asymmetric metal or polymer element so that, due to differing thermal expansion properties, the polymer tube bends and straightens when heat is applied and removed. According to some configurations, the polymer tube can be somewhat larger in diameter and in wall thickness since the stiffness (which is usually the practical limit on size) is lower for polymers than for metal tubes. 
       FIG. 9  shows a cross-section of the coiled section  106  of the metallic tube  101  having an asymmetric bi-layer metallic tube construction in accordance with various embodiments. In the embodiment shown in  FIG. 9 , the coil section  106  comprises asymmetric walled tubing  128  with at least two layers of metals  128   a  and  128   b  having differing thermal expansion properties. According to some embodiments, a first tube  128   a  is formed from a first metal and includes a lumen  120  through which a thermal transfer fluid can be transported. The first tube  128   a  is formed to have an asymmetric wall thickness. A second tube  128   b  is formed from a second metal. The second tube  128   b  is formed to have an asymmetric wall thickness and a lumen dimensioned to receive the first tube  128   b . The dimensions of the first and second tubes  128   a  and  128   b , including wall thicknesses, can be selected to achieve desired expansion and shape change attributes. 
     A bonding material may be used to secure the first and second tubes  128   a  and  128   b  together, although frictional forces between the two tubes  128   a  and  128   b  may provide sufficient bonding. The asymmetric walled tubing  128  may include insulation  124  to thermally insulate the side of the coiled section  106  oriented away from the vessel wall for reasons previously discussed. 
     According to various embodiments, the thickest portion of the asymmetric walls of the first and second tubes  128   a  and  128   b  can be oriented in opposition to one another as is shown in  FIG. 9 . The orientation of the asymmetrical walls of the first and second tubes  128   a  and  128   b  shown in  FIG. 9  maximizes the extent of shape change of the coiled section  106  in response to temperature changes. Suitable metals having differing thermal expansion properties that can be used to fabricate the asymmetric bi-layer metallic tube  128  shown in  FIG. 9  include those discussed above with regard to the embodiments of  FIG. 8 , for example. 
       FIG. 10  shows a representative RF renal therapy apparatus  300  in accordance with various embodiments of the disclosure. The apparatus  300  illustrated in  FIG. 10  includes external electrode activation circuitry  320  which comprises power control circuitry  322  and timing control circuitry  324 . The external electrode activation circuitry  320 , which includes an RF generator, is coupled to temperature measuring circuitry  328  and may be coupled to an optional impedance sensor  326 . An ablation catheter  105  of the RF renal therapy apparatus  300  includes a shaft  90  having a lumen  92  configured to receive an expandable cooling electrode  100  of a type previously described.  FIG. 10  shows the coiled section  106  of the expandable cooling electrode  100  deployed within a patient&#39;s renal artery  12  in its ablation configuration. 
     The RF generator of the external electrode activation circuitry  320  preferably includes a pad electrode  330  that is configured to comfortably engage the patient&#39;s back or other portion of the body near the kidneys. Radiofrequency energy produced by the RF generator is coupled to the expandable cooling electrode  100  by supply and/or return tubes of the expandable cooling electrode  100  or other conductor arrangement. 
     Renal denervation therapy using the apparatus shown in  FIG. 10  is typically performed using the expandable cooling electrode  100  and the pad electrode  330  coupled to the RF generator  320 , with the RF generator  320  operating in a monopolar mode. The radiofrequency energy flows through the expandable cooling electrode  100  and perivascular space adjacent the renal artery in accordance with a predetermined activation sequence to ablate perivascular tissue which includes renal nerves. 
     In general, when renal artery tissue temperatures rise above about 113° F. (50° C.), protein is permanently damaged (including those of renal nerve fibers). If heated over about 65° C., collagen denatures and tissue shrinks. If heated over about 65° C. and up to 100° C., cell walls break and oil separates from water. Above about 100° C., tissue desiccates. 
     According to some embodiments, the electrode activation circuitry  320  is configured to control activation and deactivation of the expandable cooling electrode  100  in accordance with a predetermined energy delivery protocol and in response to signals received from temperature measuring circuitry  328 . The electrode activation circuitry  320  controls radiofrequency energy delivered to the expandable cooling electrode  100  so as to maintain the current densities at a level sufficient to cause heating of the perivascular renal tissue to at least a temperature of 55° C. 
     Temperature sensors can be situated at the expandable cooling electrode  100  to provide continuous monitoring of renal artery tissue temperatures, and RF generator power can be automatically adjusted so that target temperatures are achieved and maintained. An impedance sensor arrangement  326  may be used to measure and monitor electrical impedance during RF denervation therapy, and the power and timing of the RF generator  320  may be moderated based on the impedance measurements or a combination of impedance and temperature measurements. 
     Marker bands  314  can be placed on one or multiple parts of the expandable cooling electrode  100  and/or sheath  90  to enable visualization during the procedure. A guidewire can be used to locate the renal artery to be treated, and the sheath  90  can be advanced over the guidewire and to or through the ostium of the renal artery. A hinge mechanism  356 , such as a slotted tube portion of the sheath  90 , can be built into the distal end of the sheath  90  to facilitate navigation of the near 90° turn from the aorta into the renal artery  12 . The expandable cooling electrode  100  can then be advanced through the sheath  90  and into the renal artery. 
     The embodiments shown in the figures have been generally described in the context of intravascular-based ablation of perivascular renal nerves for control of hypertension. It is understood, however, that embodiments of the disclosure have applicability in other contexts, such as energy delivery and cooling from within other vessels of the body, including other arteries, veins, and vasculature (e.g., cardiac and urinary vasculature and vessels), and other tissues of the body, including various organs. For example, a self-expanding cooling electrode can be configured for deployment within the renal vein, and another electrode can be situated externally of the renal vein (e.g., within or near the target renal artery) or the patient. An appropriately sized self-expanding cooling electrode can be deployed in a cardiac chamber, such as the right atrium for treating reentrant tachyarrhythmias, or a cardiac vessel, such as the ostium of the pulmonary vein for treating atrial fibrillation. By way of further example, various embodiments may be configured for deployment in the urethra to treat benign prostatic hyperplasia (BPH) or to treat a tumor using an appropriately sized self-expanding cooling electrode of a type described hereinabove. 
     It is to be understood that even though numerous characteristics of various embodiments have been set forth in the foregoing description, together with details of the structure and function of various embodiments, this detailed description is illustrative only, and changes may be made in detail, especially in matters of structure and arrangements of parts illustrated by the various embodiments to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed.