Patent Grant
9192790
The present invention is related to systems and methods for denervating renal vasculature, including disruption and termination of renal sympathetic nerve activity, to improve cardiac and/or renal function.
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'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'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'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.
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.
Devices, systems, and methods of the invention are directed to delivery of focused acoustic energy to innervated vasculature for one or both of imaging and ablating the innervated vasculature. Embodiments of the invention are directed to modifying renal sympathetic nerve activity using ultrasonic denervation therapy. Embodiments of the invention are directed to ultrasonic scanning or imaging of innervated tissues that contribute to renal sympathetic nerve activity.
In accordance with various embodiments, an apparatus includes a catheter configured for deployment within a vessel proximate innervated tissue that contributes to renal sympathetic nerve activity. An acoustic transducer is provided at a distal end of the catheter and dimensioned for deployment within the vessel proximate the innervated tissue. A focusing arrangement is positioned relative to the acoustic transducer and configured to focus acoustic energy outwardly beyond an inner wall of the vessel and into the innervated tissue at or proximate an outer wall of the vessel. A controller is configured to control the acoustic transducer for at least one of scanning tissue and ablating the innervated tissue. In some embodiments, the controller is configured to selectively control the acoustic transducer for scanning tissue and ablating innervated tissue.
In other embodiments, an apparatus includes a catheter configured for deployment within a vessel proximate innervated tissue, and an acoustic transducer is provided at a distal end of the catheter and dimensioned for deployment within the vessel. A focusing arrangement is positioned relative to the acoustic transducer and configured to focus acoustic energy outwardly beyond an inner wall of the vessel and into the innervated tissue at or proximate an outer wall of the vessel. A cryoballoon is dimensioned for deployment within the vessel and configured to freeze the innervated tissue. The acoustic transducer and focusing arrangement cooperate to deliver acoustic energy to frozen innervated tissue at an intensity sufficient to disrupt nerve cells of the innervated tissue.
According to some embodiments of the invention, an apparatus for facilitating delivery of acoustic energy to innervated vasculature includes a catheter configured for intravascular deployment and an ultrasound unit coupled to the catheter. An acoustic phased array transducer is provided at a distal end of the catheter and coupled to the ultrasound unit. The phased array transducer comprises a multiplicity of acoustic elements. Driver electronics are coupled to the phased array transducer. A controller is coupled to the driver electronics and configured to control activation of each of the acoustic elements of the phased array transducer for one or both of scanning and ablating target tissue of the innervated vasculature. The ultrasound unit may be an external unit or an internal unit. The ultrasound unit may be integrated at least in part at the distal end of the catheter, and the acoustic transducer may be integral or coupled to the ultrasound unit.
In other embodiments, an apparatus for facilitating delivery of acoustic energy to innervated vasculature includes a catheter configured for intravascular deployment and an ultrasound unit coupled to the catheter. An acoustic transducer is provided at a distal end of the catheter and coupled to the ultrasound unit. The acoustic transducer is configured for high intensity focused ultrasound operation in at least a cavitation ablation mode that forms bubbles within target tissue of the innervated vasculature and work to mechanically disrupt nerve fibers and ganglia included within the target tissue upon implosion or explosion.
In accordance with some embodiments, an apparatus for facilitating delivery of acoustic energy to innervated vasculature includes an imaging device configured for scanning the innervated vasculature and locating target tissue of the innervated vasculature. A catheter is configured for intravascular deployment and is coupled to an ultrasound unit. An acoustic transducer is provided at a distal end of the catheter and coupled to the ultrasound unit. The acoustic transducer is configured to deliver acoustic energy to the target tissue sufficient to ablate the target tissue located by the imaging device.
In further embodiments, an apparatus for facilitating delivery of acoustic energy to innervated vasculature includes a catheter configured for intravascular deployment and comprises an ultrasound unit coupled to the catheter. The apparatus includes an acoustic transducer provided at a distal end of the catheter and coupled to the ultrasound unit. The acoustic transducer is configured to deliver acoustic energy to target tissue of the innervated vasculature sufficient to ablate the target tissue. A balloon arrangement is configured to encompass at least the acoustic transducer. The balloon arrangement comprises a balloon that inflates under a very low pressure of about 1 to 2 pounds per square inch (PSI) or less above an ambient pressure that is adjacent to and outside the balloon.
According to other embodiments, an apparatus for facilitating delivery of acoustic energy to innervated vasculature includes a cryoballoon arrangement dimensioned for intravascular deployment and configured to freeze target tissue of the innervated vasculature. A catheter is configured for intravascular deployment and comprises an acoustic transducer at a distal end of the catheter. The acoustic transducer is coupled to an ultrasound unit. The acoustic transducer is configured to deliver acoustic energy to the frozen target tissue sufficient to destroy nerve cells of the target tissue.
In accordance with other embodiments, an apparatus for facilitating delivery of acoustic energy to innervated vasculature includes a cryoballoon arrangement dimensioned for intravascular deployment and configured to provide cooling for the innervated vasculature, such as the renal artery. A catheter is configured for intravascular deployment and comprises an acoustic transducer at a distal end of the catheter. The acoustic transducer is coupled to an ultrasound unit. The acoustic transducer is configured to deliver acoustic energy to the target tissue sufficient to destroy nerve cells of the target tissue.
In other embodiments, an apparatus of the invention facilitates delivery of acoustic energy to innervated vasculature that includes a ganglion that contributes to renal sympathetic nerve activity. The apparatus includes a catheter configured for intravascular deployment and is coupled to an ultrasound unit. The apparatus includes an acoustic focusing arrangement and an acoustic transducer provided at a distal end of the catheter, the acoustic transducer positioned relative to the focusing arrangement. The acoustic transducer and focusing arrangement are configured to deliver acoustic energy to a target ganglion of the innervated vasculature sufficient to destroy nerve cells included within the target ganglion.
In accordance with other embodiments, an apparatus for facilitating delivery of acoustic energy to innervated vasculature includes an imaging device configured for scanning the innervated vasculature and locating target tissue of the innervated vasculature. The apparatus includes a lithotripsy device configured to deliver high-energy acoustic shockwaves to the target tissue sufficient to denervate the target tissue located by the imaging device. A cryotherapy arrangement may be included, which is dimensioned for intravascular deployment and configured to freeze the target tissue. Nerve tissue, if damaged, has the potential to regenerate, especially if the nerve containing sheath has not been disrupted. New nerve growth occurs typically through the existing nerve sheath. If the nerve sheaths are disrupted or cut, nerve regenesis to the end organ is more difficult. An apparatus that combines both a freezing action followed by a mechanical acoustic wave action has the advantage of disrupting the nerve sheaths and preventing nerve regenesis to the targeted organ.
In further embodiments, an apparatus for facilitating delivery of an ablation agent to innervated vasculature includes an imaging device configured for scanning the innervated vasculature and locating a target ganglion of the renal artery or the abdominal aorta that contributes to renal sympathetic nerve activity. A delivery catheter is dimensioned for intravascular deployment in a vessel proximate the renal artery or the abdominal aorta. The delivery catheter includes a tissue penetrating feature configured to penetrate a wall of the vessel to create an access hole and to penetrate the target ganglion. A steering mechanism is configured for steering the delivery catheter through the access hole and to an extravascular location adjacent the target ganglion. A dispensing arrangement is configured to facilitate dispensing of an ablation agent from the delivery catheter into the target ganglion, whereby the ablation agent kills nerve cells of the target ganglion sufficient to terminate renal sympathetic nerve activity. The dispensing arrangement may be configured to facilitate dispensing of a neurotoxin, a venom, a cryogenic agent, a radioactive material, or radioactive seeds.
The above summary of the present invention is not intended to describe each embodiment or every implementation of the present invention. Advantages and attainments, together with a more complete understanding of the invention, will become apparent and appreciated by referring to the following detailed description and claims taken in conjunction with the accompanying drawings.
While the invention is amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail. It is to be understood, however, that the intention is not to limit the invention to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims.
In the following description, references are made to the accompanying drawings which illustrate various embodiments of the invention. It is to be understood that other embodiments may be utilized, and structural and functional changes may be made to these embodiments without departing from the scope of the present invention.
Embodiments of the invention are directed to systems, devices, and procedures for delivering ultrasonic denervation therapy to innervated renal vasculature. Embodiments of the invention are directed to systems, devices, and procedures for denervating renal vasculature using ultrasonic denervation therapy to disrupt target tissue so that renal sympathetic nerve activity is permanently terminated. Embodiments of the invention are directed to systems, devices, and procedures for scanning or imaging innervated renal vasculature to locate target tissue for denervation and to evaluate the efficacy of ultrasonic denervation therapy delivered to the target tissue. Other approaches may be used to evaluate the effectiveness of an ultrasonic denervation treatment, such as an electrode arrangement (e.g., electrode array) arranged at spaced-apart locations relative to innervated target tissue, which can sense nerve activity along nerve fibers (and at ganglia) of the innervated target tissue.
The disclosed embodiments are generally directed to imaging and/or denervating innervated renal vascular tissue that contributes to renal function, particularly renal sympathetic nerve activity. Target innervated vasculature of the renal artery, for example, preferably includes renal nerves, renal ganglia, aortal ganglia and other nerves and ganglia that contribute to renal sympathetic nerve activity. Although preferred embodiments of the invention provide for complete and permanent termination of renal sympathetic nerve activity, various embodiments may be implemented to provide for temporary (e.g., weeks or months) cessation of renal sympathetic nerve activity.
Representative embodiments of the invention described herein are generally directed to ultrasonic imaging and denervation apparatuses and therapies involving continuous or pulsed ultrasound at frequencies well above the human audible range of hearing, which corresponds to sound in the range of about 20 hertz to 20 kHz. The term “ultrasound” is intended to apply to all acoustic energy (e.g., longitudinal or transverse, mechanical waves) with a frequency greater than 20 kHz. Ultrasonic apparatuses according to embodiments of the invention typically operate at frequencies between about 1 MHz to about 80 MHz, with many apparatuses operating at frequencies between about 2 MHz to about 5 MHz. Intravascular and intracardiac ultrasonic imaging devices generally operate in the frequency range between about 5 MHz and 60 MHz.
According to various embodiments, ultrasonic apparatuses and procedures of the invention are directed to imaging renal tissue and/or positioning an ultrasonic denervation device within the renal artery or vein, for example. Various embodiments include an intravascular (e.g., endovascular, intra-to-extra vascular, or transvascular) ultrasonic denervation device configured to provide both imaging of, and denervation therapy to, target tissue of innervated renal vasculature.
Other embodiments include an intravascular ultrasonic denervation device configured to provide denervation therapy to target tissue of innervated renal vasculature, with imaging provided by a separate device, which may be an endovascular, intra-to-extravascular, transvascular, extravascular, or extracorporeal imaging device or system.
In general, suitable scanning, imaging and/or locating apparatuses provide target depth, range, and or volume data that are used by the system computer to facilitate locating of target tissue and adjustment of various device or system parameters, such as power parameters (e.g., amplitude, frequency, continuous mode, pulse mode, etc.), focus parameters (e.g., focal length, beam spread and/or divergence, phased array pulse duration and sequencing, etc.), and operating mode (e.g., scan, denervate, and concurrent scan+denervate modes), among others.
Data associated with imaging and denervation procedures may be communicated to an external system which produces imaging data and visual information useful for positioning the ultrasonic denervation device and evaluating the efficacy of an ultrasonic denervation procedure. The external system, for example, may include a computer which includes a display. Data and visual information concerning the scanning and ultrasonic denervation therapy procedures are preferably presented on the display. The computer may include an interface for communicating with other systems and devices, including a network or server.
Various embodiments of the invention are directed to apparatuses that deliver focused acoustic energy to target tissue that causes an increase in the temperature of the target tissue to a level that disrupts nerve structures of the target tissue and prevents chronic recovery of nerve fibers/ganglion in the target tissue resulting from the burn injury. Other embodiments are directed to apparatuses that deliver focused energy to target tissue that causes mechanical disruption of target tissue and prevents chronic recovery of nerve fibers/ganglion in the target tissue resulting from the mechanical disruption (e.g., cavitation microbubbles). Preferred ultrasound apparatuses include those that achieve a desired level of disruption of target tissue while leaving adjacent or intervening tissue uninjured or negligibly injured (e.g., subject to healing without permanent adverse effects).
The frequency of acoustic energy generated by ultrasonic apparatuses of the invention is preferably selected so that acoustic energy is absorbed substantially in the wall of the renal artery, preferably the outer wall region. In some embodiments, the ultrasonic apparatus is configured to emit acoustic energy of sufficient power to raise the temperature of targeted renal artery wall tissue to above 50° C. to kill the target artery tissue and nerve/ganglion within it. In other embodiments, the ultrasonic apparatus is configured to emit acoustic energy of sufficient power to raise the temperature of targeted renal artery wall tissue to above 65° C. to reform the collagen in target artery wall tissue and mechanically change the tissue property. In further embodiments, the ultrasonic apparatus is configured to emit acoustic energy of sufficient power to raise the temperature of targeted renal artery wall tissue to between 65° C. and 100° C. to render the fat from the target tissue, and totally disrupt the target tissue and prevent chronic recovery of the nerve fibers/ganglion from the burn injury.
Embodiments of the invention are directed to an intravascular device that includes a focused ultrasonic transducer, such as a High Intensity Focused Ultrasound (HIFU) device. HIFU is a highly accurate medical technology that uses high-intensity focused ultrasound to heat and destroy target tissue rapidly. A HIFU approach can focus acoustic energy to generate heat deep within target tissue at a substantial distance from the ultrasonic transducer. An important difference between HIFU and other forms of focused energy, such as RF or radiation therapy, is that the passage of ultrasound energy through intervening tissue has no apparent cumulative effect on the intervening tissue.
According to various embodiments, a HIFU transducer is incorporated or otherwise supported by a catheter dimensioned for deployment in the renal artery, renal vein, abdominal aorta, or other vessel near the kidneys. The HIFU transducer generates ultrasound beams that can be focused on target tissue located near to, or relatively distant from, the transducer. For example, embodiments of an intravascular HIFU transducer of the present invention may be used to inject acoustic energy into target tissue located about 0.5 mm to about 90 mm away from the HIFU transducer.
In short range applications, such as renal artery denervation conducted from within the renal artery, an intravascular HIFU device may be used to inject acoustic energy into target tissue of the renal artery located about 1 mm to about 4 mm away from the HIFU transducer. In long range applications, such as renal artery denervation conducted from within the renal vein or abdominal aorta, an intravascular HIFU device may be used to inject acoustic energy into target tissue of the renal artery located about 5 mm to about 80 mm away from the HIFU transducer.
Using a HIFU transducer of the present invention, one or more focal zones at or within a location, region, or volume within target tissue can be subjected to high intensity ultrasound energy, while tissue surrounding the target tissue is subjected to much lower intensity ultrasound energy. In this manner, target tissue can be heated to a sufficiently high temperature so as to cause a desired thermal effect (e.g., ablation, coagulation, denaturation, necrosis) while tissue surrounding the target area is not subject to damaging temperatures. Due to the significant energy deposition at the focal zone, the temperature within the target tissue rises to 65° to 85° C., destroying the target tissue, which includes nerves and/or ganglia, by coagulative necrosis.
Each sonication of the ultrasonic beams emitted by the HIFU transducer treats a precisely defined portion of the target tissue. HIFU denervation may be accomplished manually, automatically, or semi-automatically. For example, renal artery denervation may be accomplished by moving an intravascular HIFU transducer arrangement within the renal artery by robotic control of the catheter to which the HIFU transducer is connected. By way of further example, renal artery denervation may be accomplished by moving (translating and/or rotating) an intravascular HIFU transducer arrangement relative to a catheter to which the HIFU transducer is connected via electronic motor control.
Ultrasonic denervation therapy using acoustic energy involves the conversion of acoustic energy into heat when acoustic energy is absorbed by target tissue. Illumination of target tissue that includes nerves and ganglia with acoustic energy, for example, leads to thermal damage of the target tissue. The diffusion of heat energy into the surrounding tissue, however, can thermally damage tissue outside the target area or volume of tissue. A cooling apparatus is preferably used to minimize thermal trauma to the surrounding tissue. Various cooling apparatuses are contemplated herein for this purpose, including cryoballoons, cryocatheters, irrigation arrangements, cooling lumens, Peltier cooling apparatuses, and blood diversion apparatuses, among others.
In embodiments that utilize focused ultrasound, such as HIFU, local cooling apparatuses may not be required or desired, because focused acoustic energy can be projected to target tissue spaced apart from the ultrasonic transducer (e.g., by 1-90 mm) without heating tissue surrounding the target tissue.
Turning now to the figures,
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
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'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 and distal structures such as the kidney 10. The primary functions of sympathetic innervation of the renal vasculature include regulation of renal blood flow, 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 T10-T12 and L1. Parasympathetic signals originate primarily at spinal segments S2-S4 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
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
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. Dilation and contraction of the distal bed of renal arterioles fed by the renal artery is similarly controlled by distal branches of the renal autonomic nerves, and these “resistance vessels” are most important in determining the total blood flow through the renal artery. Conversely, increased parasympathetic activity tends to relax the smooth muscle 34, while decreased parasympathetic activity tends to cause smooth muscle contraction.
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 renal nerve 14 is shown proximate the adventitia 36 and extending longitudinally along the renal artery 12. The main trunk of the renal nerves 14 generally lies at or adjacent the adventitia of the renal artery 12, with certain branches coursing into the media to enervate the renal artery smooth muscle. For example, renal nerves may be situated in the adventitia proximate the outer wall of the renal artery (e.g., tunica adventitia) or within the vasa vasorum, such as the vasa vasorum externae.
In various embodiments according to
It is understood that in the embodiments shown in
In other embodiments, an ultrasound unit 50 comprises an ultrasound delivery apparatus capable of transmitting acoustic energy into innervated renal vasculature that facilitates locating of renal nerves 14 and ganglia 24/22 but insufficient to significantly disrupt renal sympathetic nerve activity (e.g., insufficient to effect appreciable or permanent cessation of renal sympathetic nerve activity). In such embodiments, the ultrasound unit 50 may be used in combination with a detector to facilitate imaging and locating of target structures within or near renal artery and aortic tissue.
In further embodiments, an ultrasound unit 50 comprises an ultrasound delivery apparatus capable of transmitting acoustic energy into innervated renal vasculature that facilitates locating of renal nerves 14 and ganglia 24/22 within target tissue and transmitting acoustic energy into the target tissue that significantly disrupts renal sympathetic nerve activity, such as by permanently terminating renal sympathetic nerve activity. In other embodiments, a separate internal or external imaging device may be used to facilitate locating of renal nerves 14 and ganglia 24/22 within target tissue, and an intravascular ultrasound unit 50 is configured to transmit acoustic energy into the target tissue sufficient to significantly or permanently disrupt renal sympathetic nerve activity.
According to the embodiments shown in
The imaging system or device 53 may be external to the patient (i.e., outside the skin 47) or at least partially implantable, such as an endovascular imaging device (e.g., IVUS or intravascular ultrasound device). Suitable intravascular, transvascular, extravascular, and extracorporeal apparatuses include various MRI, laser, and ultrasound apparatuses, for example.
In other embodiments, as shown in
In various embodiments, a single transducer operates as the emitter 52 and the detector 57. In other embodiments, one transducer operates as the emitter 52 and another transducer operates as the detector 57. In further embodiments, the transducer that is configured to deliver denervation therapy is also operative as a scanning transducer. In some embodiments, separate denervation and scanning transducers are employed. It is understood that the emitter and/or receiver components shown in the figures may define single transducer elements or an array of transducer elements.
In some embodiments, for example, the ultrasound unit 50 is configured to selectively operate in a scan mode and a denervation mode, allowing the ultrasound unit 50 to locate target tissue in the scan mode and then permanently disrupt renal nerve fibers and ganglia within the target tissue in the denervation mode. Details of components and functionality that can be adapted for use in or by the ultrasound unit 50 are described in greater detail hereinbelow and disclosed in U.S. Pat. Nos. 5,344,395 and 5,601,526, which are incorporated herein by reference.
In various configurations, it is desirable to stabilize the position of the ultrasound unit 50 within the renal artery 12 so that the intensity of the acoustic energy emitted by the ultrasound unit 50 does not vary significantly with location, which could otherwise result in over-treated and under-treated regions. One approach to keeping the ultrasound unit 50 at a constant distance from the wall of the renal artery is to incorporate the ultrasound unit 50 into a balloon which can be expanded until it fills the arterial lumen, embodiments of which are discussed below with reference to
In
Locating target tissue may involve locating renal or aortic ganglia and/or artery tissue which includes renal nerves 14, such as the adventitia proximate the outer wall of the renal artery or the vasa vasorum externae. For example, one or more locating components of the ultrasound unit 50 may be used to scan the renal artery 12 or adjacent tissue that includes renal nerves and/or renal/aortal ganglia. The ultrasound unit 50 (or other locating apparatus, internal or external) may be controlled to scan for target tissue in deep layers of the adventitia and/or the vasa vasorum, such as the vasa vasorum externae which penetrates the outer adventitia (tunica adventitia). Once located, the target tissue may be treated using the ultrasound unit 50.
According to various embodiments that employ an external imager 53, such as that shown in
An MRI system of the invention may be used to accurately quantify the heating of target tissue produced by the ultrasonic emitter 52 during a renal denervation procedure. For example, the MRI system preferably identifies the ultrasound path and monitors heat rise in the target tissue. An MRI system of the invention preferably provides for high soft tissue contrast and imaging in any orientation, which enhances guiding of HIFU ablation energy to target innervated renal vasculature.
Heating, position, and other imaging information developed by the MRI system is preferably used to aid in controlling ultrasonic ablation of target tissue, particularly when using a HIFU implementation. This information may be used to provide automatic (e.g., robotic) or semi-automatic (e.g., partially robotic) control of a renal denervation procedure in real-time (or near real-time), via the MRI system computer and/or physician, respectively.
In various embodiments, a real-time interactive MRI (rtMRI) system is used to provide for concurrent imaging of target innervated renal vasculature by the MRI system and ablation of the target vasculature by the ultrasound unit 50. Embodiments of an interactive real-time MRI system include a highly parallel MRI device having upwards to 32 channels or more. For example, an MRI system of the invention may include 32-element phased arrays, which may be defined by multiple synchronized scanner-receiver subsystems. Software of the MRI system coordinates the real-time acquisition, reconstruction, and display of 32-channel images across the multiple subsystems.
Real-time, large field-of-view (FOV) imaging can be achieved by using interleaved echo-planar and single-shot fast-spin-echo pulse sequences. In one approach, parallel image acquisition is augmented by independently offsetting the frequency of different array elements to variably shift their FOV. When augmented parallel imaging is combined with conventional parallel imaging techniques, a significant increase of image acceleration factors can be achieved. Increasing the number of coils can significantly increase the FOV in two dimensions during rapid imaging, with no or negligible degradation of imaging time or spatial resolution.
Interactive real-time MRI in combination with an ultrasound unit 50 can enhance procedural safety by identifying unexpected complications early in a denervation procedure. A real-time MRI system of the invention preferably provides high tissue contrast in any orientation, which facilitates accurate locating of target tissue of the renal artery, vasa vasorum, and abdominal aorta. For example, a multi-slice, real-time MRI system may be used to guide ultrasound unit emissions across vascular tissue boundaries with high precision.
In other embodiments, an ultrasonographic imaging system 53 is used to locate target tissue, determine the depth, length, and/or width of the target tissue (e.g., for 1-D, 2-D, or 3-D imaging), and guide acoustic energy emitted by the ultrasound unit 50 to the target tissue within the renal artery 12, vasa vasorum, and abdominal aorta. In various embodiments that use high intensity focused ultrasound, Ultrasound-guided Focused Ultrasound (USgFUS) apparatuses and techniques may be used to treat innervated tissue of the renal artery. Suitable ultrasonographic systems include those configured with extracorporeal, intravascular, or transvascular imaging components.
In other embodiments, a combination of an ultrasonic device and a laser device is used to cooperatively provide imaging of, and denervation therapy to, innervated renal vasculature. According to some embodiments, one of the ultrasonic device and the laser device is used for imaging, while the other of the ultrasonic device and the laser device is used for renal denervation. The ultrasonic device or the laser device (or both, if desired) is capable of transmitting acoustic and/or optical energy into the renal artery wall sufficient to disrupt target tissue that includes renal nerves 14 and/or ganglia 24/22. The acoustic and/or optical energy is preferably sufficient to disrupt the target tissue so that renal sympathetic nerve activity is permanently terminated. Combinations of ultrasonic and laser devices that can be used cooperatively to image and denervate renal vasculature include ultrasonic and laser device combinations disclosed in previously cited commonly owned U.S. Patent Publication No. 2011/0257641, filed as U.S. Provisional Patent Application Ser. No. 61/324,163 on Apr. 14, 2010 and entitled “Phototherapy for Renal Denervation.”
In other embodiments, a combination of an ultrasonic device and a laser device is used to cooperatively provide imaging of, and denervation therapy to, innervated renal vasculature. According to some embodiments, one of the ultrasonic device and the laser device is used for imaging, while the other of the ultrasonic device and the laser device is used for renal denervation. The ultrasonic device or the laser device (or both, if desired) is capable of transmitting acoustic and/or optical energy into the renal artery wall sufficient to disrupt target tissue that includes renal nerves 14 and/or ganglia 24/22. The acoustic and/or optical energy is preferably sufficient to disrupt the target tissue so that renal sympathetic nerve activity is permanently terminated. Combinations of ultrasonic and laser devices that can be used cooperatively to image and denervate renal vasculature include ultrasonic and laser device combinations disclosed in previously cited commonly owned U.S. Patent Publication No. 2011/0257641, filed as U.S. Provisional Patent Application Ser. No. 61/324,163 on Apr. 14, 2010 and entitled “Phototherapy for Renal Denervation.”
The ultrasound unit 50 may incorporate one or more of the same or disparate emitters 52a-52c to achieve desired acoustic energy characteristics, including a desired acoustic beam pattern or geometry, beam spread, beam divergence, and/or focal length, among other characteristic. Various mechanical and electronic beam shaping or beamforming apparatuses and techniques may be used to achieve desired acoustic energy characteristics. Different acoustic energy characteristics may be required or desired depending on a number of factors, including the separation distance between the ultrasound unit 50 and the target tissue (e.g., short range vs. long range targets; intravascular vs. transvascular targets) and modes of ultrasound unit operation (e.g., scan vs. ablation modes), among others.
In various embodiments, the ultrasound unit 50 incorporates an acoustic transducer arrangement 52a that emits acoustic energy in a generally conical-shaped beam 58a that converges at a generally elliptical focal region 37 situated at a desired depth of focus, l. The ultrasonic unit 50 is positioned so that the focal region 37 is coincident with respect to target tissue that includes renal nerve fibers 14 and/or ganglion tissue 24/22. After properly positioning the ultrasonic unit 50, focused ultrasonic energy (e.g., HIFU) is transmitted to the focal region 37 at the desired depth, l, to destroy the renal nerve fibers 14 and/or ganglion tissue 24/22 within the focal region 37. An acoustic transducer arrangement 52 of the ultrasonic unit 50 may have a fixed focal length, but preferably has a variable focal length.
To ensure protection of non-targeted renal artery and aortal tissue layers during HIFU or other form of ultrasonic renal denervation, various temperature control apparatuses may be used to enhance cooling at or proximate to the ultrasound unit 50. In general, the maximum temperature of the inner wall of the renal artery may be kept below some target temperature, such as 50° C., by providing heat transfer sufficient to limit the temperature rise at the inner artery wall, while allowing for a temperature increase above the target temperature within the artery wall tissue sufficient to permanently disrupt the renal nerve fibers/ganglia.
The balloon 64 may be configured to allow blood flow within the renal artery to provide cooling of the artery wall during an ablation procedure. A perfusion balloon (e.g., fluted or channeled balloon) or a fluid diversion arrangement (e.g., longitudinal inlet/outlet ports or channels) may be used to allow perfusion of blood to cool the artery wall during ultrasonic ablation.
In other embodiments, the ultrasound unit 50 may be incorporated into a balloon 64 which can be expanded to the internal diameter of the renal artery, so that the balloon blocks or partially blocks the flow of blood. The balloon 64 can be filled with a liquid that provides good acoustic coupling between the ultrasound unit 50 and balloon wall, such as saline, D5W, or a suitable cryogenic liquid. The liquid used to fill the balloon 64 preferably allows acoustic energy emitted from the ultrasonic emitter 52 to efficiently propagate through the liquid medium and through the balloon before impinging on renal artery tissue. The liquid in the balloon 64 is preferably acoustically “transparent” to the frequencies of the acoustic energy emitted by the ultrasound unit 50.
It is desirable that the liquid supplied to the balloon 64 not be toxic and should be soluble in blood to minimize possible embolic damage if the liquid should leak out of the balloon 64. The liquid in the balloon 64 may be circulated with open or closed irrigation to keep the inner wall of the artery from being heated above 50° C. during an ultrasonic ablation procedure, while the internal tissue and nerve/ganglion of the renal artery is heated above 50° C., to disrupt the nerve function while avoiding stenosis of the renal artery wall due to the response to burn injury. The liquid may be a cooling liquid, such as a cryogenic liquid.
In the embodiment shown in
An advantage of using a balloon 64 of the type shown in
According to various embodiments, the balloon 64 or a balloon separate from the ultrasound unit 50 may be implemented to deliver cryogenic therapy to innervated renal vasculature in combination with ultrasonic ablation therapy. In some embodiments, a balloon arrangement separate from the ultrasonic device 50 is used so that a wider range of cryogenic fluids (liquids and gasses) can be used to achieve desired therapeutic temperatures. For embodiments that use a separate cryoballoon arrangement, the cryogenic fluid that fills the balloon need not be an acoustic coupling fluid, since the ultrasound unit 50 is not situated within the cryoballoon. It is noted that the ultrasound unit 50 may be situated in a separate balloon (e.g., balloon 64), and that the separate cryoballoon and balloon 64 within which the ultrasound unit 50 is situated may be supported by a common catheter or separate catheters.
Suitable cryoballoons include those that can cause renal tissue freezing and/or denervation at therapeutic temperatures ranging between approximately 0° C. and approximately −180° C. For example, embodiments of a cryoballoon may be implemented to cause renal tissue freezing and/or denervation with temperatures at the renal nerves ranging from approximately 0° C. to approximately −30° C. at the higher end, and to about −140° C. to −180° C. at the lower end. These therapeutic temperature ranges may vary based on the combined therapeutic effect of delivering cryogenic and ultrasonic denervation therapy energy to innervated target tissue of the renal artery and/or aorta. A variety of useful cryogenic fluids may be employed, including saline, a mixture of saline and ethanol, Freon or other fluorocarbons, nitrous oxide, liquid nitrogen, and liquid carbon dioxide, for example.
According to another embodiment, an ultrasound unit 50 of the type shown in
The balloon 64 shown in
The balloon 64 or other stabilizing balloon can be constructed as a compliant balloon as is known in the art. For example, balloon 64 may comprise a compliant material configured to enable the balloon 64 to inflate under a very low pressure, such as about 1 to 2 pounds per square inch (PSI) or less (e.g., 0.5 PSI or less) above an ambient pressure that is adjacent to and outside the balloon 64. The compliancy of balloon 64 preferably results in little or negligible circumferential force applied to the vessel wall, while readily allowing the balloon to conform to irregularities in the shape of the tissue of the aortal/renal vasculature, which results in more efficient delivery of cooling or cryotherapy to tissues surrounding the target tissue (i.e., renal nerve fibers and renal ganglia).
All or a portion of the balloon 64 may be made of a highly compliant material that elastically expands upon pressurization. Because the balloon 64 elastically expands from a deflated state to an inflated state, the balloon 64 has an extremely low profile in the deflated state when compared to non-compliant or semi-compliant balloons. According to some embodiments, use of high compliance materials in the construction of the balloon 64, in combination with a hinge mechanism 56 built into the catheter 51 (see, e.g., hinge 356 shown in
Suitable materials for constructing all or a portion of the balloon 64 or other balloon include thermoplastic or thermoplastic elastomers, rubber type materials such as polyurethanes, natural rubber, or synthetic rubbers. The resulting balloon may be crosslinked or non-crosslinked. Other suitable materials for constructing all or a portion of the balloon 64 include silicone, urethane polymer, low durometer PEBAX, or an extruded thermoplastic polyisoprene rubber such as a low durometer hydrogenated polyisoprene rubber. These and other suitable materials may be used individually or in combination to construct the balloon 64. Details of various materials suitable and configurations for constructing a balloon 64, a stabilizing balloon or other balloon arrangement according to various embodiments are disclosed in commonly owned U.S. Pat. No. 7,198,632, U.S. application Ser. Nos. 12/980,952, and 12/980,972, which are incorporated herein by reference.
Embodiments of the invention may incorporate selected balloon, catheter, lumen, control, and other features of the devices disclosed in the following commonly owned U.S. patents and published patent applications: U.S. Patent Publication Nos. 2009/0299356, 2009/0299355, 2009/0287202, 2009/0281533, 2009/0209951, 2009/0209949, 2009/0171333, 2008/0312644, 2008/0208182, and 2008/0058791, and U.S. Pat. Nos. 5,868,735, 6,290,696, 6,648,878, 6,666,858, 6,709,431, 6,929,639, 6,989,009, 7,022,120, 7,101,368, 7,172,589, 7,189,227, 7,198,632, and 7,220,257, which are incorporated herein by reference. Embodiments of the invention may incorporate selected balloon, catheter, and other features of the devices disclosed in U.S. Pat. Nos. 6,355,029, 6,428,534, 6,432,102, 6,468,297, 6,514,245, 6,602,246, 6,648,879, 6,786,900, 6,786,901, 6,811,550, 6,908,462, 6,972,015, and 7,081,112, which are incorporated herein by reference.
In various embodiments, the balloon 64 comprises a cryoballoon (or a separate cryoballoon may be used as previously discussed) and the ultrasound unit 50 includes one or more ultrasonic emitters 52. The balloon 64 and ultrasound unit 50 cooperate to deliver acoustic and thermal energy to target tissue 49. In some embodiments, the ultrasound unit 50 comprises an ultrasonic emitter 52 that creates lesions in the artery wall primarily through disruptive heating of target tissue. In other embodiments, the ultrasound unit 50 comprises an ultrasonic emitter 52 that creates lesions in the artery wall primarily by production of cavitation bubbles, which work to mechanically disrupt nerve fibers and ganglia with the bubbles implode or explode.
According to various embodiments, a denervation therapy procedure using the apparatus shown in
The cryoballoon 64 and/or catheter apparatus is preferably configured to allow blood to flow at or near the inner vessel wall after cryotherapy has been delivered to allow for local heating of the endothelium and adjacent tissue (e.g., intima and media tissue) while the adventitia remains frozen. Acoustic energy is preferably transmitted to the still-frozen adventitia layer (at least to deeper layers near the vessel's outer wall) to permanently disrupt renal nerves and ganglia included in the frozen tissue.
An advantage of using combined cryogenic and ultrasonic therapies for denervating renal artery and aortal tissue is that blood coagulation and embolization associated with RF ablation is avoided. Another advantage is that nerve regeneration over time that can occur when using cryotherapy alone is prevented, because of the fracturing of the renal nerve sheath resulting from mechanical disruption when using cavitation ultrasonic denervation therapy, or from thermal necrotic coagulation when using thermal ultrasonic denervation therapy, which permanently disrupts renal nerve sheaths.
With reference to
The emitter 52 of the ultrasound unit 50 may be orientated at a desired angle relative to the longitudinal axis of the shaft 88 or relative to the rail 99. For example, the ultrasound unit 50 may be orientated at an angle ranging between 0 and 90 degrees relative to the longitudinal axis of the shaft 88 or the rail 99. With the ultrasound unit 50 moving axially along a spiral path defined by the rail 99 inside the balloon 64, no scraping of the renal artery wall 12 will occur. The catheter 92 is preferably translated along the rail 99 causing the ultrasound unit 50 to rotate and create a spiral burn, which interrupts any neural transmissions passing longitudinally within the wall of the renal artery 12. As discussed above, the balloon 64 may be filled with an acoustically transparent liquid, such as a cooling liquid.
For example, the ultrasound unit 50 may be oriented at an angle of about 45° to about 135° relative to the longitudinal axis of the shaft 88. Also, the emitter 52 may be biased more toward the shaft 88 than the outer surface of the balloon 64. The ultrasound unit 50 may be configured to extend from and retract into the shaft 88 under user or robotic control, which may be of particular benefit when expanding and contracting the balloon 64. The shaft 88 and the ultrasound unit 50 may be translatable and/or rotatable within the balloon 64.
The lithotripsy machine 35 uses one or both of x-rays and ultrasound scanning to locate target tissue that includes innervated renal vasculature. The lithotripsy machine 35 generates an acoustic shockwave, which is transmitted into the body via the emitter 52. Embodiments of an extracorporeal lithotripsy system for denervating renal and aortal tissue may incorporate components and functionality disclosed in U.S. Pat. No. 6,123,679, which is incorporated herein by reference.
According to other embodiments, an intracorporeal lithotripsy system may be used to denervate renal and aortal vasculature that contributes to renal sympathetic nerve activity. An intracorporeal lithotripsy system typically includes an endoscope that is percutaneously advanced to a location within the body proximate a renal artery or the abdominal aorta. An acoustic shockwave is transmitted from an emitter 52 of the endoscope into the renal artery or the abdominal aorta to disrupt innervated target tissue. Embodiments of an intracorporeal lithotripsy system for denervating renal and aortal tissue may incorporate components and functionality disclosed in commonly owned U.S. Pat. No. 5,906,623, which is incorporated herein by reference.
In other embodiments, an intracorporeal laser lithotripsy or lasertripsy system may be used to denervate renal and aortal vasculature that contributes to renal sympathetic nerve activity. An intracorporeal lasertripsy system of the present invention includes a laser source and an optical fiber that extends along a longitudinal axis of a rigid or flexible endoscope. Laser light of an appropriate wavelength and power is transmitted from the optical fiber to a focal point or region that includes innervated renal tissue. Various types of lasertripsy systems and laser sources may be used, including systems that include a pulsed dye laser, an alexandrite laser, a neodymium laser, and a holmium laser, for example. Embodiments of an intracorporeal lasertripsy denervation system for denervating renal and aortal tissue may incorporate components and functionality disclosed in commonly owned U.S. Provisional Application Ser. No. 61/324,163, and in commonly owned U.S. Pat. No. 7,104,983, both of which are incorporated herein by reference.
In accordance with various embodiments employing acoustic or laser lithotripsy, and as further shown in
According one approach, the catheter 51 can be translated and rotated along the rail 99 to cause the ultrasound unit 50 to create a spiral burn. In another approach, an ultrasound unit 50 equipped with a focused ultrasonic emitter 52 can be rotated to create a circular or cylindrical burn without incurring undue risk of stenosis of the renal artery 12.
One advantage of creating a circular or cylindrical lesion in the renal artery wall is that the longitudinal extent of the lesion is limited, which allows for repeated denervation procedures to be performed at untreated regions of the renal artery without undue risk of artery stenosis. For example, a circular or cylindrical lesion may be created near the ostium of the renal artery, leaving the majority of renal artery tissue untreated. Should additional renal denervation be required, a subsequent circular or cylindrical lesion may be created near the center or distal end of the renal artery. A mapping of renal artery lesion locations for a given patient may be stored to aid in avoiding previously treated regions of the artery when performing a subsequent ablation procedure.
The ultrasound unit 50 shown in
A one-shot treatment approach according to the embodiment shown in
It is noted that, in some embodiments, the ultrasound unit 50 can be coupled to the catheter 51 using a coupling arrangement that allows the ultrasound unit 50 to be rotated relative to the catheter 51. A manual or motorized apparatus may be controlled to cause rotation of the ultrasound unit 50 relative to the catheter 51. In other embodiments, the ultrasound unit 50 may be coupled to the catheter 51 such that rotation of the catheter 51 causes rotation of the ultrasound unit 50.
In the embodiment shown in
A cooling arrangement may be incorporated in the embodiments of
Different embodiments of phased array acoustic emitter arrangements that can be incorporated in ultrasound units 50 of the invention are shown in
In the embodiment shown in
Adjacent an outer circumference of the phased array transducer 52a is an acoustic lens 78, as is shown in
The phased array transducer 52a shown in
For example, a HIFU ultrasonic emitter 52a that incorporates one or more ultrasonic phased array transducers 52a may include 10 or less ultrasonic elements 52b to as many as 1,000 elements 52b or more (e.g., ≧24, ≧64, ≧256, ≧512, ≧768, or ≧1024 individual elements 52b may be incorporated in ultrasonic phased array transducers 52a according to various embodiments).
HIFU phased array driving electronics can be adapted to control the phase and amplitude of individual ultrasonic elements 52b using an appropriate number of control channels. For example, a HIFU ultrasonic emitter 52a may include up to 1024 discrete ultrasonic elements 52b each controlled by a separate channel with 2 ns phase resolution, 8-bit amplitude resolution, operate over a frequency range of 1 to 5 MHz, and deliver between 8 and 15 W of power to each channel.
The use of a large number of ultrasonic elements and control channels allows for the elimination of mechanical motion components of conventional single-element and array HIFU systems. For example, a HIFU phased array transducer 52a that incorporates a large number of ultrasonic elements and channels can simulate movement of the array using various known subaperture focusing techniques. A HIFU phased array transducer 52a may be electronically controlled to generate sufficiently high HIFU intensities at foci of spherical or cylindrical geometries and at a desired depth within innervated renal tissue.
It is noted that curvilinear or convex sector phased arrays may be used as an alternative to, or in concert with, a linear phased array configuration. A curvilinear phased array operates in the same manner as the linear array in that the scan lines are directed perpendicular to the transducer face. The acoustic beams generated by curvilinear or convex sector phased arrays are typically focused, rather than steered.
The power level and frequency range may be selected to provide for both scanning (e.g., lower power) and ablating (e.g., higher power) of innervated renal tissue. Although the acoustic power and transducer efficiency will vary among ultrasound transducer implementation, it is desirable that power levels corresponding to focal peak intensities equal to or greater than about 2000 W/cm2 in target tissue be achieved, which are capable of producing coagulative necrosis in the target tissue.
With reference to
The diameter and frequency of the transducer element 66 and the characteristics of the focusing lens 67 on the front of the transducer element 66 are preferably selected to maximize the intensity of acoustic power in the wall of the renal artery, which makes efficient use of the available power, reduces collateral damage, and makes the lesion relatively insensitive to small changes in the spacing from the transducer face to the artery wall. A temperature sensing element 69 may be provided and positioned to contact the transducer element 66 to monitor its temperature and prevent overheating. An acoustic backing layer 68 may be provided on the transducer element 66 to broaden the bandwidth of the transducer element 66 and to minimize the need for the ultrasound driver (not shown) to adapt the drive frequency to the ultrasound unit 50, which is typically a disposable element.
As was discussed above, the transducer element 66 may be operated in a scan mode, such as an A-scan mode or a B-scan mode as is understood in the art. Operating in the scan mode allows the system computer to diagnostically detect the range to the artery wall and potentially the thickness of the wall, and adapt the ultrasonic power and velocity of catheter translation so that a lesion of desired depth can be accomplished by the computer in the ultrasonic power drive unit.
Operating the ultrasound unit 50 in the scan mode allows the physician to see the lesion forming and estimate its depth intermittently or continuously. For example, the transducer element 66 may transmit continuously for a period during which the tissue in range will heat up. The transducer element 66 can then transmit a relatively short pulse and “listen” for the echoes as the system functions as an A-scan ultrasonic imager. The transducer element 66 can then detect the artery walls, lesion depth, and bubbles resulting from disruptive cavitation within the target tissue, and adjust the power strategy as desired. The transducer element 66 can then continue to transmit continuously for a period of time at the same or a modified transmit power.
It is noted that the ultrasound unit 50 may incorporate multiple transducers 52. In these configurations, some of the transducers 52 can operate continuously in a scan mode, while other transducers 52 can be operated continuously, intermittently, or sequentially in an cavitation ablation mode. For example, an ultrasound unit 50 may incorporate multiple transducers 52 that are arranged to produce a spiral lesion at the desired depth in the wall of the renal artery while the ultrasound unit 50 remains stationary within the lumen of the renal artery. This configuration provides for a “one-shot” denervation therapy approach in accordance with various embodiments of the invention.
With further reference to
With a planar disk transducer 52, the ultrasound intensity is approximately constant near the transducer 52 and then drops faster as the range exceeds the diameter of the disk transducer element 66. A mechanism is preferably employed to stabilize the disk transducer element 66 so that its plane is parallel to the renal artery. It is also preferably to maintain the distance between the disk transducer element 66 and the artery wall approximately constant as the disk transducer 52 is translated and rotated.
The planar disk transducer 52 shown in
The beam angle of an ultrasonic disk transducer 52 will be normal to the disk transducer element 66 and centered on the axis of the disk transducer element 66. The beam angle, BA, shown in
Sin theta=1.2V/(DF)
where theta is the half angle of the diverging beam (DB) in the far field, V is the sound velocity in the material, D is the diameter of the transducer element 66, and F is the frequency of the transducer 52.
Rotating the barrel shaped transducer 52 controls which angular section of the renal artery will be treated. Translating a masked barrel shaped transducer 52 will produce a spiral lesion if continuously on, or a spiral of spots within the renal artery wall if powered intermittently. It is desirable to use a centering mechanism to insure that the barrel shaped transducer 52 is centered in the lumen of the renal artery because the ultrasound power intensity decreases as the square of the distance from the center if the barrel transducer element 66 is longer than the inner diameter of the artery. It is also desirable to provide for cooling of the barrel transducer element 66, since its efficiency is typically not more than about 40%. Cooling can be accomplished by allowing blood to flow past the transducer 52 or by providing cooling liquid such as saline or D5W, which can be closed or open irrigated.
The beam angle, BA, of a barrel shaped cylindrical transducer 52 will be normal to the axis of the cylinder defining the transducer element 66 and will diverge with a beam, DB, which has one angle in the plane which intersects the axis of the cylinder and a second angle in the plane perpendicular to the first plane. The angle (DB) in the first plane is similar to that calculated above. The angle in the second plane is related to the diameter of the barrel of the transducer element 66, but the effective diameter is only about half as wide because ultrasound cannot be transmitted much off the normal, which makes the beam divergence about twice as great.
For either of the ultrasonic transducers 66 shown in
It is noted that the ultrasound units 50 shown in
As previously discussed, the ultrasound unit 50 may be operated to scan the adventitia 36 and vasa vasorum for renal nerves 14 and ganglia 24/22 using relatively low power acoustic energy. The ultrasound unit 50 may also be operated to deliver relatively high power acoustic energy to create lesions that permanently disrupt the target renal nerve 14. Employment of an ultrasound unit 50 that includes a HIFU emitter 52a advantageously spares tissues of the intima 32 and media 33 from injury.
It is generally known that a typical renal artery of a human adult has a diameter of about 5 mm. Embodiments of ultrasonic emitter and lens arrangements described herein may be implemented to project acoustic energy to foci having a depth of focus ranging between about 1 mm to about 10 mm, which is sufficient to reach target tissues of the renal artery wall, including ganglia, and the vasa vasorum proximate the outer wall of the renal artery.
In various embodiments, an ultrasonic emitter 52a may be implemented to project acoustic energy to foci having a depth of focus that falls within a target range that encompasses the outer adventitial layers of the renal artery. In other embodiments, an ultrasonic emitter 52a may be implemented to project acoustic energy to foci having a depth of focus that falls within a target range that encompasses the outer adventitial layers of the renal artery and the vasa vasorum proximate the outer wall of the renal artery. It is understood that ultrasonic emitter and lens arrangements may be configured for projecting acoustic energy to foci having a depth of focus that falls within a target range that encompasses renal nerves of the renal artery's ostium and ganglia of the abdominal aorta.
According to various embodiments, a multiplicity of disparate ultrasonic emitter and/or lens arrangements may be used to project acoustic energy to multiple foci having different depths of focus. Particular ones of the multiplicity of arrangements may be selectively operated for scanning and/or ablating at different tissue depths. For example, scanning at different depths within the outer renal artery wall and adjacent vasa vasorum can be performed to locate target tissue that includes one or both of renal nerves and ganglia. After determining the target tissue location and depth, which may alternatively be accomplished using a separate internal or external imager, a selected one or more of the ultrasonic emitter and/or lens arrangements may be used to ablate the target tissue at the determined depth.
The ultrasound delivery apparatus shown in
According to various embodiments, acoustic energy produced by the ultrasonic source 150 is directed to a focusing arrangement 154. The focusing arrangement 154 may include one or more acoustic lenses for shaping and directing acoustic energy received from the ultrasonic source 150 to target tissue 49, such as renal artery tissue which includes a renal nerve 14. The acoustic energy exiting the focusing arrangement 154 and penetrating the target tissue 49 is preferably a focused ultrasonic beam 62 of sufficient intensity to permanently disrupt renal nerves 14 included in the target tissue 49. An imager 53 (external or internal) is preferably used to facilitate positioning of an ultrasound unit of the ultrasound delivery apparatus, and may also be used to determine or adjust various operating parameters, such as acoustic energy intensity, duty cycle, frequency, beam shape, beam direction, axial depth, and longitudinal resolution, for example.
In some embodiments, target renal artery tissue 49 can be heated using focused acoustic energy 62, and, if the artery wall tissue temperature exceeds 50° C., the tissue can be killed. However, the target tissue 49 will not be physically and permanently disrupted until the temperature of the target tissue 49 exceeds about 65° C., where the collagen reforms. With focused acoustic energy beams 62, a small focus can be achieved deep in target tissues 49, such as a focal region or volume within the adventitia tunica or vasa vasorum that includes a renal nerve or ganglion. When the temperature within the target tissue 49 reaches a sufficient level (e.g., >65° C.), the target tissue 49 is thermally coagulated (e.g., coagulative necrosis). By focusing at more than one tissue location or by scanning the focused beam, a volume of target tissue can be thermally ablated.
Other embodiments of the invention are directed to an ultrasound source 150 and a focusing arrangement 154 configured for operation in a cavitation ablation mode. Operating the ultrasound source 150 and focusing arrangement 154 in a cavitation ablation mode, for example, is preferably accomplished by transmitting a string of high intensity, low duty cycle acoustic energy pulses into the target tissue 49. Embodiments of the invention are also directed to an ultrasound source 150 and focusing arrangement 154 that is selectively operable in a cavitation ablation mode and a scan mode, allowing the ultrasound unit to locate target renal artery tissue in one mode and then permanently disrupt renal nerve fibers and ganglia within the target tissue in a second mode.
In accordance with other embodiments, acoustic energy produced by the ultrasonic source 150 may be used for imaging tissues of the renal and aortal vasculature. In ultrasonic imaging applications, the intensity of the acoustic energy is less than that required for ablation, and is preferably low enough to avoid thermal injury to scanned tissue.
In the embodiment shown in
The controller 151 of the ultrasound system may be configured to generate a 2D image by controlling the sweep of the ultrasonic beam 62. The ultrasound source 150 may be swept mechanically, such as by rotating or swinging. In another approach, a 1D phased array ultrasound source 150 may be used to sweep the ultrasonic beam 62 electronically. The received data is processed by the computer 164 and used to construct the image. This image is a 2D representation of a slice into the renal artery or abdominal aorta. 3D images can be generated in real-time by acquiring a series of adjacent 2D images, such as by using one or more 2D phased array ultrasonic transducers that sweep the ultrasonic beam 62.
The ultrasound system may be operated in one or more scanning modes. In an A-scan mode, for example, a single ultrasonic transducer is used to scan a line through the renal artery tissue with the echoes plotted on a display as a function of depth. In a B-scan mode, a linear array of ultrasonic transducers are used to simultaneously scan a plane through the renal artery tissue that can be viewed as a two-dimensional image on the display.
When positioned within the patient's renal vein 42, as also shown in
The ultrasound unit 50 includes an ultrasonic emitter 52 that can be operated in a denervation mode and, optionally, a scanning mode. In this representative illustration, the ultrasonic emitter 52 is operated in a scan mode to aid in locating target tissue, such as aorticorenal ganglion 22 and renal ganglion 24.
After locating the target tissue, the ultrasonic emitter 52 or another imaging device (external or internal) is used to determine the range to the target tissue. The ultrasonic emitter 52 is focused electronically (e.g., via a subaperture or electronic focus or steering technique) or mechanically at the target tissue based on the range information. Acoustic energy is transmitted to the target tissue sufficient to permanently denervate the target tissue, by use of thermal or cavitation ablation modes.
It is noted that an ultrasound unit 50 in accordance with various embodiments of the invention may incorporate multiple ultrasonic devices for purposes of imaging and/or ablating target tissue. Some of the ultrasonic devices, for example, can operate continuously in a scan mode, while other ultrasonic devices can be operated continuously, intermittently, or sequentially in an ablation mode.
According to some embodiments, an intravascular imaging catheter 105 is delivered to a location within a patient's renal artery 12, typically accessed via the inferior abdominal aorta 20. The intravascular imaging catheter 105 preferably includes an imaging device 107, such as an IVUS device or other ultrasonic imaging device, or a laser imaging device, such as a laser transducer or other optical imaging device. With the imaging device 107 properly positioned in or proximate the renal artery 12, the delivery catheter 101 is advanced into the renal vein 42, typically accessed via the inferior vena cava 40. The delivery catheter 101 preferably includes a steering mechanism. Suitable steering mechanisms that can be incorporated in a delivery catheter 101 of the present invention include various mechanisms incorporated into known steerable guide catheters.
The delivery catheter 101 includes a tissue penetrating feature at its distal tip, such as tissue piercing tip 103, to aid in creating an access hole 102 in the renal vein 42. Alternatively, an energy source, for example radiofrequency or laser, may be applied at the catheter tip to assist in puncturing the wall of the renal vein 42. With aid from the imaging catheter 105 or external imager 53, the delivery catheter 101 is advanced through the access hole 102 and navigated around the exterior of the renal artery 12 to a location adjacent a target ganglion, such as a renal ganglion 24.
Using the tissue piercing tip 103, the delivery catheter 101 is forcibly advanced so that a portion of the distal tip of the delivery catheter 101 penetrates into the renal ganglion 24. An ablation agent is delivered to ganglion tissue via the delivery catheter 101. The ablation agent is preferably effective in killing nerve fibers of the renal ganglion 24, so that all renal sympathetic nerve activity associated with the renal ganglion 24 is permanently terminated.
In some embodiments, the delivery catheter 101 includes a lumen which is fluidly coupled to a distal port and a proximal port of the delivery catheter 101. The proximal port is coupled to an ablation agent source, and the distal port is configured to dispense an ablation agent from the distal tip of the delivery catheter 101. In other embodiments, a cavity of the distal tip of the delivery catheter 101 contains an ablation agent, which may be a fluid, a solid, or a soluble mixture or matrix. The ablation agent may be eluted or otherwise communicated from the cavity of the distal tip of the delivery catheter 101 into the renal ganglion 24.
The delivery catheter 101 may be configured to deliver a variety of ablation agents via an ablation dispensing arrangement (e.g., lumen and port system, distal tip cavity). The ablation agent may take the form of a pharmacological agent or mixture of agents (e.g., a neurotoxin or venom), a thermal transfer fluid (hot or cold), or radioactive material or seeds (e.g., iodine-125 or palladium-103 for low dosage rate brachytherapy, iridium-192 for high dose rate brachytherapy). A variety of cryogens may be employed as ablation agents, including cold saline or cold saline and ethanol mixture, Freon or other fluorocarbon refrigerants, nitrous oxide, liquid nitrogen, and liquid carbon dioxide, for example. Alternatively, DC, AC, or RF electrical current may be dispensed from tip 103 via a lead that passes through lumen 102 to heat tissue or alter tissue sufficiently for ablation.
After delivering the ablation agent to the renal ganglion 24, the delivery catheter 101 can be navigated to another ganglion, such as the aorticorenal ganglion 22, the superior mesenteric ganglion, or the celiac ganglia or plexus. The imaging catheter 107 is preferably moved to an appropriate intravascular location to aid navigation and positioning of the delivery catheter 101, such as a location within the abdominal aorta 20 or renal vein 40.
One or more physiologic parameters can be monitored during the procedure to determine the effect of the ablation agent on the patient's renal sympathetic nerve activity. For example, an electrode arrangement may be situated in contact with the inner or outer wall of the renal artery 12 near opposing sides of the renal ganglion 24. The electrode arrangement may be configured to measure nerve impulses transmitted along renal nerve fibers that couple to or pass through the renal ganglion 24. By way of further example, one or more physiological parameters that are sensitive to changes in renal sympathetic nerve activity may be monitored, and the efficacy of the ablation agent at the renal ganglion 24 may be determined based on measured changes in the physiological parameter(s). Suitable apparatuses for these purposes are disclosed in commonly owned U.S. Patent Publication No. 2008/0234780 and in U.S. Pat. No. 6,978,174, which are incorporated herein by reference.
It is noted that marker bands can be placed on one or multiple parts of the catheter 105 and/or 101 to enable visualization during the delivery, imaging, and/or denervation procedures. The marker bands may be solid or split bands of platinum or other radiopaque metal, for example.
Referring now to
The catheter's shaft may be formed to include an elongate core member 357 and a tubular member 353 disposed about a portion of the core member 357. The tubular member 353 may have a plurality of slots 361 formed therein. The slotted hinge region 356 of the catheter's shaft may be configured to have a preferential bending direction.
For example, the tubular member 352 may have a plurality of slots 361 that are formed by making a pair of cuts into the wall of tubular member 361 that originate from opposite sides of tubular member 353, producing a lattice region of greater flexibility relative to the proximal and distal sections 352, 354 of the catheter's shaft. The thickness of the catheter wall at the hinge region 356 can be varied so that one side of the catheter wall is thicker than the opposite side. This difference in wall thickness alone (e.g., a hinge region devoid of slots) or in combination with a difference in slot (void) density at the hinge region 356 provides for a preferential bending direction of the distal portion of the catheter 51.
A hinge arrangement 356 constructed to provide for a preferential bending direction allows a physician to more easily and safely navigate the ultrasound unit 50 to make the near 90 degree turn into the renal artery from the abdominal aorta, for example. One or more marker bands may be incorporated at the hinge region 356 to provide visualization of this region of the catheter's shaft during deployment. Details of useful hinge arrangements that can be incorporated into embodiments of a catheter 51 of the present invention or other component that facilitates access to the renal artery/vein from the abdominal aorta are disclosed in U.S. Patent Publication Nos. 2008/0021408 and 2009/0043372, which are incorporated herein by reference. It is noted that the catheter 51 may incorporate a steering mechanism in addition to, or exclusion of, a hinge arrangement 356. Known steering mechanisms incorporated into steerable guide catheters may be incorporated in various embodiments of a catheter 51 of the present invention.
The discussion provided herein concerning degrees of induced renal nerve damage, temperature ranges, amount of energy delivered into target tissue, and other embodiment details presented in this disclosure are provided for non-limiting illustrative purposes. Actual therapeutic parameters associated with the denervation apparatuses and methodologies may vary somewhat or significantly from those described herein, and be impacted by a number of factors, including patient-specific factors (e.g., the patient's unique renal vasculature and sympathetic nervous system characteristics), refractoriness to drugs impacting renal function, type and technology of the therapy device(s), therapy duration and frequency, use of a single therapy device or multiplicity of therapy devices (in sequential or concurrent use), structural characteristics of the therapy device(s) employed, and other implementation and physiologic particulars, among others.
The foregoing description of the various embodiments of the invention has been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of the above teaching. For example, the devices and techniques disclosed herein may be employed in vasculature of the body other than renal vasculature, such as coronary and peripheral vessels and structures. By way of further example, embodiments of an ultrasonic denervation unit may be implemented for chronic use, and structures other than a catheter, such as a stent, may be used to maintain positioning of the ultrasonic denervation unit within the renal artery or other vessel. It is intended that the scope of the invention be limited not by this detailed description, but rather by the claims appended hereto.
This application claims the benefit of Provisional Patent Application Ser. No. 61/324,164 filed on Apr. 14, 2010, to which priority is claimed pursuant to 35 U.S.C. §119(e) and which is hereby incorporated herein by reference in its entirety.
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| Number | Date | Country | |
|---|---|---|---|
| 20110257523 A1 | Oct 2011 | US |
| Number | Date | Country | |
|---|---|---|---|
| 61324164 | Apr 2010 | US |
