|Publication number||US20040082859 A1|
|Application number||US 10/611,838|
|Publication date||Apr 29, 2004|
|Filing date||Jun 30, 2003|
|Priority date||Jul 1, 2002|
|Also published as||US20130072928, US20130131668|
|Publication number||10611838, 611838, US 2004/0082859 A1, US 2004/082859 A1, US 20040082859 A1, US 20040082859A1, US 2004082859 A1, US 2004082859A1, US-A1-20040082859, US-A1-2004082859, US2004/0082859A1, US2004/082859A1, US20040082859 A1, US20040082859A1, US2004082859 A1, US2004082859A1|
|Original Assignee||Alan Schaer|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (20), Referenced by (88), Classifications (22), Legal Events (1)|
|External Links: USPTO, USPTO Assignment, Espacenet|
 The present application is a non-provisional of U.S. Patent Application Serial No. 60/419,317 (Attorney Docket No. 021574-000210), filed Oct. 16, 2002, which contained the entire content of prior Provisional Application No. 60/393,339 (Attorney Docket No. 21574-000200), filed on Jul. 1, 2002, with additional material added, the full disclosures of which are incorporated herein by reference.
 1. Field of the Invention
 In a general sense, the invention is directed to systems and methods for treating interior tissue regions of the body. More specifically, the invention is directed to systems and methods for treating dysfunction in body sphincters and adjoining tissue, e.g., in and around the lower esophageal sphincter and cardia of the stomach.
 2. Description of the Background Art
 The gastrointestinal (GI) tract extends from the mouth to the anus, and includes the esophagus, stomach, small and large intestines, and rectum. Along the way, ring-like muscle fibers called sphincters control the passage of food from one specialized portion of the GI tract to another. The GI tract is lined with a mucosal layer about 1-2 mm thick that absorbs and secretes substances involved in the digestion of food and protects the body's own tissue from self-digestion. The esophagus is a muscular tube that extends from the pharynx through the esophageal hiatus of the diaphragm to the stomach. Peristalsis of the esophagus propels food toward the stomach as well as clears any refluxed contents of the stomach.
 The junction of the esophagus with the stomach is controlled by the lower esophageal sphincter (LES), a thickened circular ring of smooth esophageal muscle. The LES straddles the squamocolumnar junction, or z-line—a transition in esophageal tissue structure that can be identified endoscopically. At rest, the LES maintains a high-pressure zone between 10 and 30 mm Hg above intragastric pressures. The LES relaxes before the esophagus contracts, and allows food to pass through to the stomach. After food passes into the stomach, the LES constricts to prevent the contents from regurgitating into the esophagus. The resting tone of the LES is maintained by muscular and nerve mechanisms, as well as different reflex mechanisms, physiologic alterations, and ingested substances. Transient LES relaxations may manifest independently of swallowing. This relaxation is often associated with transient gastroesophageal reflux in normal people. Muscular contractions of the diaphragm around the esophageal hiatus during breathing serve as a diaphragmatic sphincter that offers secondary augmentation of lower esophageal sphincter pressure to prevent reflux.
 The stomach stores, dissolves, and partially digests the contents of a meal, then delivers this partially digested food across the pyloric sphincter into the duodenum of the small intestine in amounts optimal for maximal digestion and absorption. Feelings of satiety are influenced by the vagally modulated muscle tone of the stomach and duodenum as well as through the reception and production of biochemicals (e.g., hormones) therein, particularly the gastric antrum.
 Finally, after passage of undigested food into the large intestine, it is passed out of the body through the anal sphincter. Fluids unused by the body are passed from the kidneys into the bladder, where a urinary sphincter controls their release.
 A variety of diseases and ailments arise from the dysfunction of a sphincter. Dysfunction of the lower esophageal sphincter, typically manifest through transient, relaxations, leads to reflux of stomach acids into the esophagus. One of the primary causes of the sphincter relaxations is believed to be aberrant vagally-mediated nerve impulses to the LES and cardia (upper part of the stomach). This condition, called Gastroesophageal Reflux Disease (GERD), creates discomfort such as heartburn and with time can begin to erode the lining of the esophagus—a condition that can progress to esophagitis and a pre-cancerous condition known as Barrett's Epithelium. Complications of the disease can progress to difficulty and pain in swallowing, stricture, perforation and bleeding, anemia, and weight loss. Dysfunction of the diaphragmatic sphincter, such as that caused by a hiatal hernia, can compound the problem of LES relaxations. It has been estimated that approximately 7% of the adult population suffers from GERD on a daily basis. The incidence of GERD increases markedly after the age of 40, and it is not uncommon for patients experiencing symptoms to wait years before seeking medical treatment.
 Treatment of GERD includes drug therapy to reduce or block stomach acid secretions, and/or increase LES pressure and peristaltic motility of the esophagus. Most patients respond to drug therapy, but it is palliative in that it does not cure the underlying cause of sphincter dysfunction, and thus requires lifelong dependence. Invasive abdominal surgical intervention has been shown to be successful in improving sphincter competence. One procedure, called Nissen fundoplication, entails invasive, open abdominal surgery. The surgeon wraps the gastric fundis about the lower esophagus, to, in effect, create a new “valve.” Less invasive laparoscopic techniques have also been successful in emulating the Nissen fundoplication. As with other highly invasive procedures, antireflux surgery is associated with the risk of complications such as bleeding and perforation. In addition, a significant proportion of individuals undergoing laparascopic fundoplication report difficulty swallowing (dysphagia), inability to vomit or belch, and abdominal distention.
 In response to the surgical risks and drug dependency of patients with GERD, new trans-oral endoscopic technologies are being evaluated to improve or cure the disease. One approach is the endoscopic creation and suturing of folds, or plications, in the esophageal or gastric tissue in proximity to the LES, as described by Swain, et al, [Abstract], Gastrointestinal Endoscopy, 1994; 40:AB35. Another approach, as described in U.S. Pat. No. 6,238,335, is the delivery of biopolymer bulking agents into the muscle wall of the esophagus. U.S. Pat. No. 6,112,123 describes RF energy delivery to the esophageal wall via a conductive medium. Also, as described in U.S. Pat. No. 6,056,744, RF energy has been delivered to the esophageal wall via discrete penetrating needles. The result is shrinkage of the tissue and interruption of vagal afferent pathways some believe to play a role in the transient relaxations of the LES.
 The above endoscopic techniques all require the penetration of the esophageal wall with a needle-like device, which entails the additional risks of perforation or bleeding at the puncture sites. Special care and training by the physician is required to avoid patient injury. Use of the plication technique requires many operational steps and over time sutures have been reported to come loose and/or the tissue folds have diminished or disappeared. Control of the amount and location of bulking agent delivery remains an art form, and in some cases the agent has migrated from its original location. RF delivery with needles requires careful monitoring of impedance and temperature in the tissue to prevent coagulation around the needle and associated rapid increases in temperature. Lesion size is also limited by the needle size. Limitations of the design require additional steps of rotating the device to achieve additional lesions. Physicians have to be careful not to move the device during each of the multiple one-minute energy deliveries to ensure the needles do not tear the tissue.
 Dysfunction of the anal sphincter leads to fecal incontinence, the loss of voluntary control of the sphincter to retain stool in the rectum. Fecal incontinence is frequently a result of childbearing injuries or prior anorectal surgery. In most patients, fecal incontinence is initially treated with conservative measures, such as biofeedback training, alteration of the stool consistency, and the use of colonic enemas or suppositories. Biofeedback is successful in approximately two-thirds of patients who retain some degree of rectal sensation and functioning of the external anal sphincter. However, multiple sessions are often necessary, and patients need to be highly motivated. Electronic home biofeedback systems are available and may be helpful as adjuvant therapy. Several surgical approaches to fecal incontinence have been tried, with varying success, when conservative management has failed. These treatments include sphincter repair, gracilis or gluteus muscle transposition to reconstruct an artificial sphincter, and sacral nerve root stimulation. The approach that is used depends on the cause of the incontinence and the expertise of the surgeon. Surgical interventions suffer from the same disadvantages discussed above with respect to GERD. An RF needle ablation device, similar in design to that described above for treatment of GERD, has been described in WO/01/80723. Potential device complications and use limitations are similar to those described for GERD.
 Dysfunction of the urinary sphincter leads to urinary incontinence, the loss of voluntary control of the sphincter to retain urine in the bladder. In women this is usually manifest as stress urinary incontinence, where urine is leaked during coughing, sneezing, laughing, or exercising. It occurs when muscles and tissues in the pelvic floor are stretched and weakened during normal life events such as childbirth, chronic straining, obesity, and menopause. In men, urinary incontinence is usually a result of pressure of an enlarged prostate against the bladder.
 U.S. Pat. No. 6,073,052 describes a method of sphincter treatment using a microwave antennae and specific time and temperature ranges, and 6,321,121 a method of GERD treatment using a non-specific energy source, with limited enabling specifications. The use of ultrasound energy for circumferential heating of the pulmonary vein to create electrical conduction block has been described in U.S. Pat. No. 6,012,457 and U.S. Pat. No. 6,024,740. The use of ultrasound for tumor treatments has been described in U.S. Pat. No. 5,620,479.
 In view of the foregoing, and notwithstanding the various efforts exemplified in the prior art, there remains a need for a more simple, rapid, minimally invasive approach to treating sphincters that minimizes risk to the patient.
 The present invention seeks to heat sphincter tissues using ultrasound energy. The preferred method is to use ultrasound energy to heat tissue and thus create necrotic regions (lesions) in the tissue. The lesions tighten the tissue by shrinking it (through dessication, protein denaturation, and disruption of collagen bonds), and/or bulking it (with new collagen formation). The lesions also prevent or delay opening of the sphincter by reducing the compliance of the tissue in either or both the radial and longitudinal directions as the sphincter is forced to expand and shorten when the internal pressure increases. The lesions also interrupt nerve pathways responsible for sphincter relaxations. In general, during the heating process, the invention employs means to minimize heat damage to the mucosal layer of the sphincter. However, in the case of Barrett's Esophagus, selective heating of the intestinal metaplasia on the luminal surface of the esophagus is preferred. Ultrasound may also be used (continuously or in pulsed mode) to create shock waves that cause mechanical disruption through cavitation that create the desired tissue effects. While this invention relates broadly to many tissue sphincters in the body, the focus of the disclosure will be on the treatment of a dysfunctional lower esophageal sphincter (LES) responsible for GERD.
 The key advantage of an ultrasound ablation system over others is that a uniform annulus of tissue can be heated simultaneously. Alternatively, the transducers can be designed so that only user-defined precise regions of the circumference are heated. Ultrasound also penetrates tissue deeper than RF or simple thermal conduction, and therefore can be delivered with a more uniform temperature profile. Thus lesions can be created at deeper locations than could be safely achieved with RF needles puncturing the tissue. Similarly, the deeper heating and uniform temperature profile also allow for an improved ability to create a cooling gradient at the surface. Relatively low power can be delivered over relatively long durations to maximize tissue penetration but minimize surface heating. If only surface heating is desired, as in the case of Barrett's Esophagus, the acoustic energy can be focused at or just before the tissue surface. Another means to selectively heat the tissue surface is to place a material against the tissue, between the tissue and the transducer, that selectively absorbs acoustic energy and preferentially heats at the tissue interface. A device using ultrasound for ablation may also be configured to allow diagnostic imaging of the tissue to determine the proper location for therapy and to monitor the lesion formation process.
 In a first specific aspect of the present invention, methods for remodeling luminal tissue comprise positioning a vibrational transducer at a target site in a body lumen of a patient. The vibrational transducer is energized to produce acoustic energy under conditions selected to induce tissue remodeling in at least a portion of the tissue circumferentially surrounding the body lumen. In particular, the tissue remodeling may be directed at or near the luminal surface, but will more usually be directed at a location at a depth beneath the luminal surface, typically from 1 mm to 10 mm, more usually from 2 mm to 6 mm. In the case of Barrett's Esophagus, the first 1 to 3 mm of tissue depth is to be remodeled. In the most preferred cases, the tissue remodeling will be performed in a generally uniform matter on a ring or region of tissue circumferentially surrounding the body lumen, as described in more detail below.
 The acoustic energy will typically be ultrasonic energy produced by electrically exciting an ultrasonic transducer which may optionally be coupled to an ultrasonic horn, resonant structure, or other additional mechanical structure which can focus or enhance the vibrational acoustic energy. In an exemplary case, the transducer is a phased array transducer capable of selectively focusing and/or scanning energy circumferentially around the body lumen.
 The acoustic energy is produced under conditions which may have one or more of a variety of biological effects. In many instances, the acoustic energy will be produced under conditions which cause shrinkage of the tissue, optionally by heating the tissue and inducing shrinkage of the collagen. Alternatively or additionally, the acoustic energy may be produced under conditions which induce collagen formation in order to bulk or increase the mass of tissue present. Such collagen formation may in some cases, at least, result from cavitation or other injury-producing application of the vibrational energy. Thus, under some conditions, the vibrational energy will be produced under conditions which cause cavitation within the tissues. Additionally, the acoustic energy may be produced under conditions which interrupt nerve pathways within the tissue, such as the vagal nerves as described in more detail hereinafter. Add info here relating to treating intestinal metaplasia, interruption of biochemical reception and production, and prevention of food absorption.
 Preferred ultrasonic transducers may be energized to produce unfocused acoustic energy from the transducer surface in the range from 10 W/cm2 to 100 W/cm2, usually from 30 W/cm2 to 70 W/cm2. The transducer will usually be energized at a duty cycle in the range from 10% to 100%, more usually from 70% to 100%. Focused ultrasound may have much higher energy densities, but will typically use shorter exposure times and/or duty cycles. In the case of heating the tissue, the transducer will usually be energized under conditions which cause a temperature rise in the tissue to a tissue temperature in the range from 55° C. to 95° C., usually from 60° C. to 80° C. In such instances, it will usually be desirable to cool the luminal surface, which is a mucosal surface in the case of the esophagus which may treated by the present invention, in order to reduce the risk of injury.
 Usually, the vibrational transducer will be introduced to the body lumen using a catheter which carries the transducer. In certain specific embodiments, the transducer will be carried within an inflatable balloon on the catheter, and the balloon when inflated will at least partly engage the luminal wall in order to locate the transducer at a pre-determined position relative to the luminal target site. In a particular instance, the transducer is disposed within the inflatable balloon, and the balloon is inflated with an acoustically transmissive material so that the balloon will both center the transducer and enhance transmission of acoustic energy to the tissue. In an alternative embodiment, the transducer may be located between a pair of axially spaced-apart balloons. In such instances, when the balloons are inflated, the transducer is centered within the lumen. Usually, an acoustically transmissive medium is then introduced between the inflated balloons to enhance transmission of the acoustic energy to the tissue. In any of these instances, the methods of the present invention optionally comprise moving the transducer relative to the balloons, typically in an axially direction, in order to focus or scan the acoustic energy at different locations on the luminal tissue surface.
 In specific embodiments, the acoustically transmissive medium may be cooled in order to enhance cooling of the luminal tissue surface. Additionally, the methods may further comprise monitoring temperature of the luminal tissue surface and/or at a point beneath the luminal tissue surface.
 In other specific examples, methods of the present invention further comprise focusing acoustic energy beneath the luminal tissue surface. Or in the case of Barrett's Esophagus, acoustic energy is focused at or just before the luminal tissue surface. In such instances, focusing may be achieved using a phased array (by selectively energizing particular elements of the array) and the tissue may be treated at various locations and various depths.
 The methods as described above are particularly preferred for treating patients suffering from gastroesophageal reflex disease (GERD) where the acoustic energy remodels the tissue surrounding a lower esophageal sphincter (LES). In other instances, the methods of the present invention may be used to treat patients suffering hiatal hernias, where the acoustic energy is directed at tissue surrounding a diaphragmatic sphincter above the LES, to treat the anal sphincter for incontinent patients, to remodel tissues of the bladder neck and surrounding endopelvic fascia for urinary stress incontinence, etc. Further, the methods of the present invention can be used to induce feelings of satiety in obese patients, where acoustic energy is delivered to regions of the stomach and small intestine to interrupt or modify vagal mediation of muscle tone, or to block or modify the reception and production of biochemicals that affect satiety. The acoustic energy may also be used to selectively necrose or shrink tissue in the pylorus to delay gastric emptying and prolong the sensation of fullness. Acoustic energy may also be used to render regions of tissue unable to absorb food.
 The methods of the present invention may further comprise introducing a cannula to the target site, expanding a balloon on the cannula at the target site with an acoustically transmissive medium, and selectively directing the vibrational transducer within the balloon to remodel targeted tissue. The balloon can provide a relatively large working space and optionally can seal an opening to the body lumen, such as to the esophagus. Optionally, a viewing scope or other viewing means can be introduced into the balloon on the cannula to allow visualization of the tissue being treated. In such cases, the acoustically transmissive medium should also be transparent. Within the inflated balloon, the transducer on the catheter may be manipulated in a variety of ways, including deflecting, rotating, everting, and the like, in order to direct the vibrational energy precisely where desired. Alternatively or additionally, phased array and other circumferential array transducers may be axially translated to otherwise selectively positioned to achieve a desired therapy. When used at the end of the esophagus or at another opening to a body lumen, the balloon on the cannula may be expanded to cover the entire opening or alternatively may be expanded over a location adjacent to the opening.
 In other embodiments, directing the transducer may comprise selectively pivoting at least one transducer from a fixed location on the catheter or otherwise within the balloon, optionally comprising deflecting at least two catheters from spaced-apart locations. In such cases, the two transducers may be used together in order to focus energy at particular location(s) within the target tissue.
 In yet another aspect of the present invention, positioning the transducer may comprise capturing luminal tissue between opposed elements on the catheter where the transducer is disposed on at least one of the elements. The energy may then be directed from the transducer into the captured tissue. Capturing may comprise clamping the tissue between moveable elements and/or applying a vacuum to the tissue to draw tissue between the opposed elements.
 The present invention still further comprises apparatus for remodeling the lower esophageal sphincter. Such apparatus comprise a catheter or probe adapted to be esophageally introduced to the lower esophageal sphincter and a vibrational transducer on the catheter. The transducer is adapted to deliver acoustic energy to the tissue of the LES in order to lessen gastroesophageal reflux. Apparatus for treating other sphincters may also be provided for certain sphincters such as the anal sphincter. The apparatus may comprise a more rigid probe instead of a highly flexible catheter.
 Specific apparatus constructions include providing an inflatable balloon on the catheter, where the balloon is adapted when inflated to position the catheter within the LES so that the transducer can deliver energy to the LES. The transducer is usually positioned coaxially within the balloon, and means may be provided for inflating the balloon with an acoustically transmissive medium.
 Alternatively, the transducer may be positioned between a pair of axially-spaced-apart balloons, where the apparatus will typically further comprise means for delivering an acoustically transmissive medium between the balloons. In all instances, the apparatus may further comprise means for cooling the acoustically transmissive medium, and means for axially translating the transducer relative to the catheter. In certain specific examples, the transducer comprises a phased array transducer.
 The present invention may further comprise systems including apparatus as set forth above in combination with a cannula having a channel for receiving and deploying the catheter of the apparatus. Usually, the systems will further include a viewing scope or other imaging component which is either part of the cannula or introducable through the cannula.
 In preferred embodiments, the cannula further comprises an inflatable balloon formed over a distal end thereof, where the catheter is extendable from the cannula into the balloon when the balloon is inflated. In such embodiments, the vibrational transducer on the catheter is preferably deflectable, rotatable, and/or evertable within the balloon when inflated to allow a high degree of selective positioning of the transducer. Alternatively, the vibrational transducer may comprise a circumferential array which is axially translatable or otherwise positionable on the catheter when the balloon is inflated. Still further optionally, the transducer(s) may comprise pivotally mounted transducers on the catheter to permit separate or focused positioning of the transducers. Still further alternatively, the transducer(s) may be mounted on a pair of spaced-apart elements on the catheter, where the elements are configured to receive target tissue therebetween. Usually, the elements will be movable to clamp tissue therebetween and/or a vacuum source will be provided on the catheter to selectively draw tissue into the space between the spaced-apart elements.
FIG. 1 is an illustration of the tissue structures comprising the esophagus and stomach.
FIG. 2 is an Ultrasound Ablation System for GERD Treatment.
FIG. 3 is an Ultrasound Ablation Catheter.
FIG. 4a illustrates the diagnostic endoscopic procedure used to identify the target treatment area.
FIG. 4b illustrates the delivery of the tissue treatment apparatus.
FIG. 5 illustrates the positioning of the ultrasound transducer and balloon at the region of the lower esophageal sphincter.
FIG. 6 illustrates the positioning of the “rear-directed” ultrasound transducer and balloon distal to the lower esophageal sphincter for delivering energy to the inferior aspect of the lower esophageal sphincter and the cardia.
FIG. 7 is a preferred pattern of completely circumferential lesions.
FIG. 8 is a preferred pattern of groups of discrete lesions formed in circumferential groups.
FIG. 9 is a cylindrical PZT material.
FIG. 10 is an annular array of flat panel transducers and the acoustic output from the array.
FIG. 11 is isolated active sectors of a transducer formed by isolating the plated regions.
FIG. 12 is a selective plating linked with continuous plating ring.
FIG. 13 is a cylindrical transducer with non-resonant channels.
FIG. 14 is a cylindrical transducer with an eccentric core.
FIG. 15 is a cylindrical transducer with curved cross-section and resulting focal region of acoustic energy.
FIG. 16 is an illustration of acoustic output from conical transducers.
FIG. 17 is a longitudinal array of cylindrical transducers.
FIG. 18 is a transducer mounting configuration using metal mounts.
FIG. 19 shows transducer geometry variations used to enhance mounting integrity.
FIG. 20 is transducer plating variations used to enhance mounting integrity.
FIG. 21 shows cooling flow through the catheter center lumen, exiting the tip.
FIG. 22 shows cooling flow recirculating within the catheter central lumen.
FIG. 23 shows cooling flow circulating within the balloon.
FIG. 24 shows cooling flow circulating within a lumen/balloon covering the transducer.
FIG. 25 shows cooling flow circulating between an inner and an outer balloon.
FIG. 26 is an ultrasound ablation element bounded by tandem occluding members.
FIG. 27 shows sector occlusion for targeted ablation and cooling.
FIG. 28 shows thermocouples incorporated into proximally slideable splines positioned over the outside of the balloon.
FIG. 29 shows thermocouples incorporated into splines fixed to the shaft but tethered to the distal end with an elastic member.
FIG. 30 shows thermocouples attached to the inside of the balloon, aligned with the ultrasound transducer.
FIG. 31 shows thermocouples positioned on the outside of the balloon, aligned with the ultrasound transducer, and routed across the wall and through the inside of the balloon.
FIGS. 32a-32 c show the use of a slit in the elastic encapsulation of a thermocouple bonded to the outside of an elastic balloon that allows the thermocouple to become exposed during balloon inflation.
FIG. 33 shows thermocouples mounted on splines between two occluding balloons and aligned with the transducer.
FIG. 34a is an Ultrasound Ablation System for GERD Treatment that includes an ablation catheter with a tip controllable from a member attached to the distal tip.
FIG. 34b is an Ultrasound Ablation System for GERD Treatment that includes an ablation catheter with a tip optionally controlled via an internal tensioning mechanism.
FIG. 35 illustrates the deployment of an overtube with balloon over an endoscope.
FIG. 36 illustrates retraction of the endoscope within the balloon of the overtube.
FIG. 37 illustrates inflation of the overtube balloon at the region of the Lower Esophageal Sphincter (LES).
FIG. 38a illustrates advancement of the ablation catheter out of the endoscope.
FIG. 38b illustrates manipulation of the tip of the ablation catheter in order to direct the energy in a particular direction.
FIG. 39 illustrates lesion formation from above the LES using the preferred system.
FIG. 40 illustrates lesion formation from below the LES using the preferred system.
FIG. 41 illustrates lesion formation during the forward delivery of ultrasound from a transducer mounted on the tip of the catheter.
FIG. 42 illustrates lesion formation using the preferred catheter with one external pullwire routed through a second open channel of the endoscope. A smaller, simper overtube balloon is also used.
FIG. 43 illustrates lesion formation using a catheter advanced through an endoscope channel. No overtube is used; instead, a balloon is mounted on the catheter tip which inflates outward from the tip of the shaft.
FIG. 44 illustrates lesion formation using a deflectable or preshaped catheter advanced out on an endoscope channel. The overtube has a member extending distally from the distal opening of the overtube. The balloon is mounted at its distal end to the distal end of the member. The member has one or more lumens for fluid delivery and guide wire use.
FIG. 45 illustrates the deployment of an overtube having a doughnut shaped balloon.
FIG. 46 illustrates the lesion formation from an ultrasound ablation catheter positioned inside the doughnut shaped balloon of the overtube.
FIG. 47 illustrates lesion formation from a catheter having either or both distal and proximal ablation elements mounted within a peanut shaped balloon.
FIGS. 48a-48 d illustrate alternative means for changing the orientation of the ultrasound transducer.
FIG. 49a illustrates lesion formation from an ablation catheter while sealing the distal LES orifice with a balloon catheter.
FIG. 49b illustrates lesion formation from an ablation catheter while sealing the distal LES orifice with a balloon catheter and sealing the esophagus proximal to the LES with a balloon on an overtube.
FIG. 49c illustrates the use of a stasis valve between the overtube and endoscope to prevent fluid from flowing out the lumen between the two devices.
FIGS. 49d and 49 e illustrate different embodiments of the stasis valve mounted on the tip of the overtube.
FIG. 50 illustrates lesion formation from an ablation catheter routed through 2 available channels in the endoscope while sealing the distal LES orifice with a balloon catheter.
FIG. 51 illustrates lesion formation from an ablation catheter having a membrane surrounding the transducer while a balloon attached to the opposite side of the shaft forcing the transducer against the tissue.
FIGS. 52a and 52 b illustrate the use of an ablation device that sucks tissue in the region of the LES into a chamber where energy delivered into captured tissue.
FIGS. 53a and 53 b illustrate the use of mechanical swivel grips to draw tissue into and hold within an ablation chamber.
FIG. 53c illustrates the use of wire to press tissue into and hold within an ablation chamber.
FIG. 53d illustrates the use of inflatable doughnuts to press tissue into and hold within an ablation chamber.
 This Specification discloses various catheter-based systems and methods for treating dysfunction of sphincters and adjoining tissue regions in the body. The systems and methods are particularly well suited for treating these dysfunctions in the upper gastrointestinal tract, e.g., in the lower esophageal sphincter (LES) and adjacent cardia of the stomach. For this reason, the systems and methods will be described in this context.
 Still, it should be appreciated that the disclosed systems and methods are applicable for use in treating other dysfunctions elsewhere in the body, which are not necessarily sphincter-related. For example, the various aspects of the invention have application in procedures requiring treatment of hemorrhoids, or incontinence, or restoring compliance to or otherwise tightening interior tissue or muscle regions. The systems and methods that embody features of the invention are also adaptable for use with systems and surgical techniques that are not necessarily catheter-based.
 In general, this disclosure relates to the ability of the ultrasound to heat the tissue in order to cause it to acutely shrink and tighten. It should also be noted that another physiologic means by which the tissue may move inward after heating is through the stimulation of new collagen growth during the healing phase. Besides swelling the wall, it may also serve to strengthen the wall. Further, by necrosing viable tissue, vagal afferent pathways responsible for transient relaxations of the LES are reduced or eliminated, leading to improved tonic contraction of the LES.
 For the purposes of stimulating collagen growth, it may be sufficient to deliver shock waves to the tissue such that the tissue matrix is mechanically disrupted (i.e, via cavitation), but not necessarily heated. This is another means by which ultrasound could be a more beneficial energy modality than others. The ultrasound could be delivered in high-energy MHz pulses or through lower energy kHz or “lithotriptic” levels.
 As FIG. 1 shows, the esophagus 10 is an approximately 25 cm long muscular tube that transports food from the mouth to the stomach 12 using peristaltic contractions. Mucous is secreted from the walls of the esophagus to lubricate the inner surface and allow food to pass more easily.
 The junction of the esophagus 10 with the stomach 12 is controlled by the lower esophageal sphincter (LES) 18, a thickened circular ring of smooth esophageal muscle. The LES straddles the squamocolumnar junction, or z-line 14—a transition in esophageal tissue structure that can be identified endoscopically. An upper region of the stomach 12 that surrounds the LES 18 is referred to as the cardia 20. After food passes into the stomach 12, the LES 18 constricts to prevent the contents from regurgitating into the esophagus 10. Muscular contractions of the diaphragm 16 around the esophageal hiatus 17 during breathing serve as a diaphragmatic sphincter that offers secondary augmentation of lower esophageal sphincter pressure to prevent reflux.
 The LES 18 relaxes before the esophagus 10 contracts, and allows food to pass through to the stomach 12. After food passes into the stomach 12, the LES 18 constricts to prevent the contents from regurgitating into the esophagus 10. The resting tone of the LES 18 is maintained by muscular and nerve mechanisms, as well as different reflex mechanisms, physiologic alterations, and ingested substances. Transient LES relaxations may manifest independently of swallowing. This relaxation is often associated with transient gastroesophageal reflux in normal people.
 Dysfunction of the LES 18, typically manifest through transient relaxations, leads to reflux of stomach acids into the esophagus 10. One of the primary causes of the sphincter relaxations is believed to be aberrant vagally-mediated nerve impulses to the LES 18 and cardia 20. This condition, called Gastroesophageal Reflux Disease (GERD), creates discomfort such as heartburn and other debilitating symptoms. Dysfunction of the diaphragmatic sphincter (at the esophageal hiatus 17), such as that caused by a hiatal hernia, can compound the problem of LES relaxations.
 It should be noted that the views of the esophagus and stomach shown in FIG. 1 and elsewhere in the drawings are not intended to be strictly accurate in an anatomic sense. The drawings show the esophagus and stomach in somewhat diagrammatic form to demonstrate the features of the invention.
 As shown in FIG. 2, the present invention relates to an ablation system 30 consisting of an ablation device 32 with an acoustic energy delivery element (ultrasound transducer) 34 mounted on the distal end of the catheter. The device is delivered transorally to the region of the LES 18. The system 30 consists of the following key components:
 1. A catheter shaft 36 with proximal hub 38 containing fluid ports 40, electrical connectors 42, and optional central guidewire lumen port 44.
 2. An ultrasound transducer 34 that produces acoustic energy 35 at the distal end of the catheter shaft 36
 3. An expandable balloon 46 operated with a syringe 48 used to create a fluid chamber 50 that couples the acoustic energy 35 to the tissue 60
 4. Temperature sensor(s) 52 in the zone of energy delivery
 5. An energy generator 70 and connector cable(s) 72 for driving the transducer and displaying temperature values
 6. A fluid pump 80 delivering cooling fluid 82.
 As shown in FIG. 3, the preferred embodiment of the ablation device consists of an ultrasound transducer 34 mounted within the balloon 46 near the distal end of an elongated catheter shaft 36. A proximal hub, or handle, 38 allows connections to the generator 70, fluid pump 80, and balloon inflation syringe 48. In other embodiments (not shown) the hub/handle 38 may provide a port for a guidewire and an actuator for deflection or spline deployment. The distal tip 39 is made of a soft, optionally preshaped, material such as low durometer silicone or urethane to prevent tissue trauma. The ultrasound transducer 34 is preferably made of a cylindrical ceramic PZT material, but could be made of other materials and geometric arrangements as are discussed in more detail below. Depending on performance needs, the balloon 46 may consist of a compliant material such as silicone or urethane, or a more non-compliant material such as nylon or PET, or any other material having a compliance range between the two. Temperature sensors 52 are aligned with the beam of acoustic energy 35 where it contacts the tissue. Various configurations of temperature monitoring are discussed in more detail below. The catheter is connected to an energy generator 70 that drives the transducer at a specified frequency. The optimal frequency is dependent on the transducer 34 used and is typically in the range of 7-10 MHz, but could be 1-40 MHz. The frequency may be manually entered by the user or automatically set by the generator 70 when the catheter is connected, based on detection algorithms in the generator. The front panel of the generator 70 displays power levels, delivery duration, and temperatures from the catheter. A means of detecting and displaying balloon inflation volume and/or pressure, and cooling flow rate/pressure may also be incorporated into the generator. Prior to ablation, the balloon 46 is inflated with a fluid such as saline or water, or an acoustic coupling gel, until it contacts the esophagus over a length exceeding the transducer length. Cooling fluid 82 is used to minimize heat buildup in the transducer and keep the mucosal surface temperatures in a safe range. In the preferred embodiment shown, cooling fluid 82 is circulated in through the balloon inflation lumen 51 and out through the central lumen 53 using a fluid pump 80. As described later, the circulation fluid may be routed through lumens different than the balloon lumen, requiring a separate balloon inflation port 39. Also, it may be advantageous to irrigate the outer proximal and/or distal end of the balloon to cool it and to ensure the expulsion or air on the outer edges of the balloon that could interfere with the coupling of the ultrasound into the tissue. The path of this irrigating fluid could be from a lumen in the catheter and out through ports proximal and/or distal to the balloon, or from the inner lumen of a sheath placed over the outside of or alongside the catheter shaft.
 In other embodiments (not shown) of the catheter, the central lumen 53 could allow passage of a guidewire (i.e., 0.035″) from a proximal port 44 out the distal tip 39 for atraumatic placement into the body. Alternatively, a monorail guidewire configuration could be used, where the catheter 30 rides on the wire just on the tip section 39 distal to the transducer 34. A central lumen with open tip configuration would also allow passage of an endoscope for visualization during the procedure. The catheter could also be fitted with a pull wire connected to a proximal handle to allow deflection to aid in placement through the mouth and down the esophagus. This could also allow deflection of an endoscope in the central lumen. The balloon may also be designed with a textured surface (i.e., adhesive bulbs or ribs) to prevent movement in the inflated state. Finally, the catheter shaft or balloon or both could be fitted with electrodes that allow pacing and electrical signal recording within the esophagus.
 The above ablation device 32 is configured as an elongated catheter. Of course, depending on the sphincter being treated, the ablation device may be configured as a probe, or a surgically delivered instrument.
 In use (see FIGS. 4a, 4 b, 5 and 6), the patient lies awake but sedated in a reclined or semi-reclined position. If used, the physician inserts an esophageal introducer 92 through the throat and partially into the esophagus 10. The introducer 92 is pre-curved to follow the path from the mouth, through the pharynx, and into the esophagus 10. The introducer 92 also includes a mouthpiece 94, on which the patient bites to hold the introducer 92 in position. The introducer 92 provides an open, unobstructed path into the esophagus 10 and prevents spontaneous gag reflexes during the procedure.
 The physician need not use the introducer 92. In this instance, a simple mouthpiece 94, upon which the patient bites, is used.
 The physician preferably first conducts a diagnostic phase of the procedure, to localize the site to be treated. As FIG. 4a shows, a visualization device can be used for this purpose. The visualization device can comprise an endoscope 96, or other suitable visualizing mechanism, carried at the end of a flexible catheter tube 98. The catheter tube 98 for the endoscope 96 includes measured markings 97 along its length. The markings 97 indicate the distance between a given location along the catheter tube 98 and the endoscope 96.
 The physician passes the catheter tube 98 through the patient's mouth and pharynx, and into the esophagus 10, while visualizing through the endoscope 96. Relating the alignment of the markings 97 to the mouthpiece 94, the physician can gauge, in either relative or absolute terms, the distance between the patient's mouth and the endoscope 96 in the esophagus 10. When the physician visualizes the desired treatment site (lower esophageal sphincter 18 or cardia 20) with the endoscope 96, the physician records the markings 97 that align with the mouthpiece 94.
 The physician next begins the treatment phase of the procedure. As shown in FIG. 4b, the physician passes the catheter shaft 36 carrying the ultrasound transducer 34 through the introducer 92. For the passage, the expandable balloon 46 is in its collapsed condition. The physician can keep the endoscope 96 deployed for viewing the expansion and fit of the balloon 46 with the tissue 60, either separately deployed in a side-by-side relationship with the catheter shaft 36, or (as will be described later) by deployment through a lumen in the catheter shaft 36 or advancement of the catheter 32 through a lumen in the endoscope 96 itself and expansion of the balloon distal to the endoscope 96. If there is not enough space for side-by-side deployment of the endoscope 96, the physician deploys the endoscope 96 before and after expansion of the balloon 46.
 As illustrated in FIG. 4b, the catheter shaft 36 includes measured markings 99 along its length. The measured markings 99 indicate the distance between a given location along the catheter shaft 36 and the ultrasound transducer 34. The markings 99 on the catheter shaft 36 correspond in spacing and scale with the measured markings 97 along the endoscope catheter tube 98. The physician can thereby relate the markings 99 on the catheter shaft 36 to gauge, in either relative or absolute terms, the location of the ultrasound transducer 34 inside the esophagus 10. When the markings 99 indicate that the ultrasound transducer 34 is at the desired location (earlier visualized by the endoscope 96), the physician stops passage of the ultrasound transducer 34. The ultrasound transducer 34 is now located at the site targeted for treatment.
 In FIG. 5, the targeted site is shown to be the lower esophageal sphincter 18. In FIG. 6, the targeted site is shown to be the cardia 20 of the stomach 12.
 Once located at the targeted site, the physician operates the syringe 48 to convey fluid or coupling gel into the expandable balloon 46. The balloon 46 expands to make intimate contact with the mucosal surface, either with the sphincter (see FIG. 5) or the cardia 20 (FIG. 6) over a length longer than where the acoustic energy 35 impacts the tissue. The balloon is expanded to temporarily dilate the lower esophageal sphincter 18 or cardia 20, to remove some or all the folds normally present in the mucosal surface, and to create a chamber 50 of fluid or gel through which the acoustic energy 35 couples to the tissue 60. The expanded balloon 46 also places the temperature sensors 52 in intimate contact with the mucosal surface.
 The physician commands the energy generator 70 to apply electrical energy to the ultrasound transducer 34. The function of the ultrasound transducer 34 is to then convert the electrical energy to acoustic energy 35.
 The energy heats the smooth muscle tissue below the mucosal lining. The generator 70 displays temperatures sensed by the temperature sensors 80 to monitor the application of energy. The physician may choose to reduce the energy output of the generator 70 if the temperatures exceed predetermined thresholds. The generator 70 may also automatically shutoff the power if temperature sensors 80 or other sensors in the catheter exceed safety limits.
 Prior to energy delivery, it will most likely be necessary for the physician to make use of a fluid pump 80 to deliver cooling fluid 82 to keep the mucosal temperature below a safe threshold. This is discussed in more detail later. The pump 80 may be integrated into the generator unit 70 or operated as a separate unit.
 Preferably, for a region of the lower esophageal sphincter 18 or cardia 20, energy is applied to achieve tissue temperatures in the smooth muscle tissue in the range of 55° C. to 95° C. In this way, lesions can typically be created at depths ranging from one 1 mm below the mucosal surface to as far as the outside wall of the esophagus 10. Typical acoustic energy densities range 10 to 100 W/cm2 as measured at the transducer surface. For focusing elements, the acoustic energy densities at the focal point are much higher.
 It is desirable that the lesions possess sufficient volume to evoke tissue-healing processes accompanied by intervention of fibroblasts, myofibroblasts, macrophages, and other cells. The healing processes results in a contraction of tissue about the lesion, to decrease its volume or otherwise alter its biomechanical properties. Replacement of collagen by new collagen growth may also serve to bulk the wall of the sphincter. The healing processes naturally tighten the smooth muscle tissue in the sphincter 18 or cardia 20. Ultrasound energy typically penetrates deeper than is possibly by RF heating or thermal conduction alone.
 With a full circumferential output of acoustic energy 35 from ultrasound transducer 34, it is possible to create a completely circumferential lesion 100 in the tissue 60 of the LES 18. To create greater lesion density in a given targeted tissue area, it is also desirable to create a pattern of multiple circumferential lesions 102 a spaced axially along the length of the targeted treatment site in the LES 18 or cardia 20 (above and below the z-line 14, as shown in FIG. 7. Preferably, a pattern of 4 circumferential lesions 102 a is desired spaced 1 cm apart, with 2 above the z-line 14, and 2 below; however, the safe and effective range may be just one or higher, depending on how the lesions form and heal. As shown in FIG. 6, the use of a “rear directed” ultrasound beam also allows treatment of the inferior aspect of the LES 18 and the cardia 20.
 To limit the amount of tissue ablated, and still achieve the desired effect, it may be beneficial to spare and leave viable some circumferential sections of the esophageal wall. To this end, the ultrasound transducer 34 can be configured (embodiments of which are discussed in detail below) to emit ultrasound in discrete locations around the circumference. Various lesion patterns 102 b can be achieved. A preferred pattern (shown in FIG. 8 for the esophagus 10) comprises several rings 104 of lesions 106 about 5 mm apart, each ring 104 comprising preferably 8 (potential range 1-16) lesions 106. For example, a preferred pattern 102 b comprises six rings 104, 3 above and 3 below the z-line 14, each with eight lesions 106.
 The physician can create a given ring pattern (either fully circumferential lesions or discrete lesions spaced around the circumference) 100 by expanding the balloon 46 with fluid or gel, pumping fluid 82 to cool the mucosal tissue interface as necessary, and delivering electrical energy from the generator 70 to produce acoustic energy 35 to the tissue 90. The lesions in a given ring (100 or 104) can be formed simultaneously with the same application of energy, or one-by-one, or in a desired combination. Additional rings of lesions can be created by advancing the ultrasound transducer 34 axially, gauging the ring separation by the markings 99 on the catheter shaft 36. Other, more random or eccentric patterns of lesions can be formed to achieve the desired density of lesions within a given targeted site.
 The catheter 32 can also be configured such that once the balloon 46 is expanded in place, the distal shaft 36 upon which the transducer 34 is mounted can be advanced axially within the balloon 46 that creates the fluid chamber 35, without changing the position of the balloon 46. Preferably, the temperature sensor(s) 52 move with the transducer 34 to maintain their position relative to the energy beam 35.
 The distal catheter shaft 36 can also be configured with multiple ultrasound transducers 34 and temperature sensors 52 along the distal axis in the fluid chamber 35 to allow multiple rings to be formed simultaneously or in any desired combination. They can also simply be formed one-by-one without having to adjust the axial position of the catheter 32.
 To achieve certain heating effects, it may be necessary to utilize variations of the transducer, balloon, cooling system, and temperature monitoring. For instance, in order to prevent ablation of the mucosal lining of the esophagus 10, it may be necessary to either (or both) focus the ultrasound under the surface, or sufficiently cool the surface during energy delivery. To treat Barrett's Esophagus, the ultrasound may be focused at or just before the tissue surface. The balloon material, or an additional material adjacent to the balloon between the tissue and the transducer may be made of sufficient dimensions and acoustic properties to selectively absorb energy at the tissue interface. Materials having good acoustic absorption properties include silicone and polyurethane rubbers, and oil suspensions. Increasing the frequency of the transducer will also aid in confining acoustic absorption at the surface. Temperature monitoring provides feedback as to the how well the tissue is being heated and cooled.
 The following sections describe various embodiments of the ultrasound transducer 34 design, the mounting of the ultrasound transducer 34, cooling configurations, and means of temperature monitoring.
 Ultrasound Transducer Design Configurations: In one preferred embodiment, shown in FIG. 9, the transducer 34 is a cylinder of PZT (i.e., PZT-4, PZT-8) material 130. The material is plated on the inside and outside with a conductive metal, and poled to “flip”, or align, the dipoles in the PZT material 130 in a radial direction. This plating 120 allows for even distribution of an applied potential across the dipoles. It may also be necessary to apply a “seed” layer (i.e., sputtered gold) to the PZT 130 prior to plating to improve plating adhesion. The dipoles (and therefore the wall of the material) stretch and contract as the applied voltage is alternated. At or near the resonant frequency, acoustic waves (energy) 35 emanate in the radial direction from the entire circumference of the transducer. The length of the transducer can be selected to ablate wide or narrow regions of tissue. The cylinder is 5 mm long in best mode, but could be 2-20 mm long. Inner diameter is a function of the shaft size on which the transducer is mounted, typically ranging from 1 to 4 mm. The wall thickness is a function of the desired frequency. An 8 MHz transducer would require about a 0.011″ thick wall.
 In another embodiment of the transducer 34 design, illustrated in FIG. 10, multiple strips 132 of PZT 130 or MEMS (Micro Electro Mechanical Systems—Sensant, Inc., San Leandro, Calif.) material are positioned around the circumference of the shaft to allow the user to ablate selected sectors. The strips 132 generally have a rectangular cross section, but could have other shapes. Multiple rows of strips could also be spaced axially along the longitudinal axis of the device. By ablating specific regions, the user may avoid collateral damage in sensitive areas, or ensure that some spots of viable tissue remain around the circumference after energy delivery. The strips 132 may be all connected in parallel for simultaneous operation from one source, individually wired for independent operation, or a combination such that some strips are activated together from one wire connection, while the others are activated from another common connection. In the latter case, for example, where 8 strips are arranged around the circumference, every other strip (every 90°) could be activated at once, with the remaining strips (90° C. apart, but 45° C. from the previous strips) are activated at a different time. Another potential benefit of this multi-strip configuration is that simultaneous or phased operation of the strips 132 could allow for regions of constructive interference (focal regions 140) to enhance heating in certain regions around the circumference, deeper in the tissue. Phasing algorithms could be employed to enhance or “steer” the focal regions 140. Each strip 132 could also be formed as a curved x-section or be used in combination with a focusing lens to deliver multiple focal heating points 140 around the circumference.
 The use of multiple strips 132 described above also allows the possibility to use the strips for imaging. The same strips could be used for imaging and ablation, or special strips mixed in with the ablation strips could be used for imaging. The special imaging strips may also be operated at a different frequency than the ablation strips. Since special imaging strips use lower power than ablation strips, they could be coated with special matching layers on the inside and outside as necessary, or be fitted with lensing material. The use of MEMs strips allows for designs where higher resolution “cells” on the strips could be made for more precise imaging. The MEMs design also allows for a mixture of ablation and imaging cells on one strip. Phasing algorithms could be employed to enhance the imaging.
 In another embodiment of the transducer 34 design, shown in FIG. 11, a single cylindrical transducer 34 as previously described is subdivided into separate active longitudinal segments 134 arrayed around the circumference through the creation of discrete regions of inner plating 124 and outer plating 126. To accomplish this, longitudinal segments of the cylindrical PZT material 130 could be masked to isolate regions 127 from one another during the plating process (and any seed treatment, as applicable). Masking may be accomplished by applying wax, or by pressing a plastic material against the PZT 130 surface to prevent plating adhesion. Alternatively, the entire inner and outer surface could be plated followed by selective removal of the plating (by machining, grinding, sanding, etc.). The result is similar to that shown in FIG. 10, with the primary difference being that the transducer is not composed of multiple strips of PZT 130, but of one continuous unit of PZT 130 that has different active zones electrically isolated from one another. Ablating through all at once may provide regions of constructive interference (focal regions 140) deeper in the tissue. Phasing algorithms could also be employed to enhance the focal regions 140.
 As described above, this transducer 34 can also be wired and controlled such that the user can ablate specific sectors, or ablate through all simultaneously. Different wiring conventions may be employed. Individual “+” and “−” leads may be applied to each pair of inner 124 and outer 126 plated regions. Alternatively, a common “ground” may be made by either shorting together all the inner leads, or all the outer leads and then wiring the remaining plated regions individually.
 Similarly, it may only be necessary to mask (or remove) the plating on either the inner 124 or the outer 126 layers. Continuous plating on the inner region 124, for example, with one lead extending from it, is essentially the same as shorting together the individual sectors. However, there may be subtle performance differences (either desirable or not) created when poling the device with one plating surface continuous and the other sectored.
 In addition to the concept illustrated in FIG. 11, it may be desirable to have a continuous plating ring 128 around either or both ends of the transducer 34, as shown in FIG. 12 (continuous plating shown on the proximal outer end only, with no discontinuities on the inner plating). This arrangement could be on either or both the inner and outer plating surface. This allows for one wire connection to drive the given transducer surface at once (the concept in FIG. 11 would require multiple wire connections).
 Another means to achieve discrete active sectors in a single cylinder of PZT is to increase or decrease the wall thickness (from the resonant wall thickness) to create non-resonant and therefore inactive sectors. The entire inner and outer surface can be then plated after machining. As illustrated in FIG. 13, channels 150 are machined into the transducer to reduce the wall thickness from the resonant value. As an example, if the desired resonant wall thickness is 0.0110″, the transducer can be machined into a cylinder with a 0.0080″ wall thickness and then have channels 150 machined to reduce the wall thickness to a non-resonant value (i.e., 0.0090″). Thus, when the transducer 34 is driven at the frequency that resonates the 0.0110″ wall, the 0.0090″ walls will be non-resonant. Or the transducer 34 can be machined into a cylinder with a 0.015″ wall thickness, for example, and then have selective regions machined to the desired resonant wall thickness of, say, 0.0110″. Some transducer PZT material is formed through an injection molding or extrusion process. The PZT could then be formed with the desired channels 150 without machining.
 Another way to achieve the effect of a discrete zone of resonance is to machine the cylinder such that the central core 160 is eccentric, as shown in FIG. 14. Thus different regions will have different wall thicknesses and thus different resonant frequencies.
 It may be desirable to simply run one of the variable wall thickness transducers illustrated above at a given resonant frequency and allow the non-resonant walls be non-active. However, this does not allow the user to vary which circumferential sector is active. As a result, it may be desirable to also mask/remove the plating in the configurations with variable wall thickness and wire the sectors individually.
 In another method of use, the user may gain control over which circumferential sector is active by changing the resonant frequency. Thus the transducer 34 could be machined (or molded or extruded) to different wall thicknesses that resonate at different frequencies. Thus, even if the plating 122 is continuous on each inner 124 and outer 126 surface, the user can operate different sectors at different frequencies. This is also the case for the embodiment shown in FIG. 10 where the individual strips 132 could be manufactured into different resonant thicknesses. There may be additional advantages of ensuring different depths of heating of different sectors by operating at different frequencies. Frequency sweeping or phasing may also be desirable.
 For the above transducer designs, longitudinal divisions are discussed. It is conceivable that transverse or helical divisions would also be desirable. Also, while the nature of the invention relates to a cylindrical transducer, the general concepts of creating discrete zones of resonance can also be applied to other shapes (planar, curved, spherical, conical, etc.). There can also be many different plating patterns or channel patterns that are conceivable to achieve a particular energy output pattern or to serve specific manufacturing needs.
 Except where specifically mentioned, the above transducer embodiments have a relatively uniform energy concentration as the ultrasound propagates into the tissue. The following transducer designs relate to configurations that focus the energy at some depth. This is desirable to minimize the heating of the tissue at the mucosal surface but create a lesion at some depth.
 One means of focusing the energy is to apply a cover layer “lens” 170 (not shown) to the surface of the transducer in a geometry that causes focusing of the acoustic waves emanating from the surface of the transducer 34. The lens 170 is commonly formed out an acoustically transmissive epoxy that has a speed of sound different than the PZT material 130 and/or surrounding coupling medium. The lens 170 could be applied directly to the transducer, or positioned some distance away from it. Between the lens 170 and the transducer may be a coupling medium of water, gel, or similarly non-attenuating material. The lens could be suspended over (around) the transducer 34 within the balloon 46, or on the balloon itself.
 In another embodiment, the cylindrical transducer 34 can be formed with a circular or parabolic cross section. As illustrated in FIG. 15, this design allows the beam to have focal regions 140 and cause higher energy intensities within the wall of the tissue.
 In another embodiment shown in FIG. 16, angled strips or angled rings (cones) allow forward and/or rear projection of ultrasound (acoustic energy 35). Rearward projection of ultrasound 35 may be particularly useful to heat the underside of the LES 18 or cardia 20 when the transducer element 34 is positioned distal to the LES 18. Each cone could also have a concave or convex shape, or be used with a lensing material 170 to alter the beam shape. In combination with opposing angled strips or cones (forward 192 and rearward 194) the configuration allows for focal zones of heating 140.
 In another embodiment, shown in FIG. 17, multiple rings (cylinders) of PZT transducers 34 would be useful to allow the user to change the ablation location without moving the catheter. This also allows for regions of constructive/destructive interference (focal regions 140) when run simultaneously. Anytime multiple elements are used, the phase of the individual elements may be varied to “steer” the most intense region of the beam in different directions. Rings could also have a slight convex shape to enhance the spread and overlap zones, or a concave shape to focus the beam from each ring. Pairs of opposing cones or angled strips (described above) could also be employed. Each ring could also be used in combination with a lensing material 170 to achieve the same goals.
 Transducer Mounting: One particular challenge in designing transducers that deliver significant power (approximately 10 acoustic watts per cm2 at the transducer surface, or greater) is preventing the degradation of adhesives and other heat/vibration sensitive materials in proximity to the transducer. If degradation occurs, materials under or over the transducer can delaminate and cause voids that negatively affect the acoustic coupling and impedance of the transducer. In cases where air backing of the transducer is used, material degradation can lead to fluid infiltration into the air space that will compromise transducer performance. Some methods of preventing degradation are described below.
 In FIG. 18, a preferred means of mounting the transducer 34 is to securely bond and seal (by welding or soldering) the transducer to a metal mounting member 200 that extends beyond the transducer edges. Adhesive attachments 202 can then be made between the mounting member 200 extensions remote to the transducer 34 itself. The mounting member(s) can provide the offsets from the underlying mounting structure 206 necessary to ensure air backing between the transducer 34 and the underlying mounting structure 206. One example of this is shown in FIG. 18 where metal rings 200 are mounted under the ends of the transducer 34. The metal rings 200 could also be attached to the top edges of the transducer 34, or to a plated end of the transducer. It may also be possible to mechanically compress the metal rings against the transducer edges. This could be accomplished through a swaging process or through the use of a shape-memory material such as nitenol. It may also be possible to use a single metal material under the transducer as the mounting member 200 that has depressions (i.e. grooves, holes, etc.) in the region under the transducer to ensure air backing. A porous metal or polymer could also be placed under the transducer 34 (with the option of being in contact with the transducer) to provide air backing.
 In FIG. 19, another means of mounting the transducer 34 is to form the transducer 34 such that non-resonating portions 210 of the transducer 34 extend away from the central resonant section 212. The benefit is that the non-resonant regions 210 are integral with the resonant regions 212, but will not significantly heat or vibrate such that they can be safely attached to the underlying mounting structure 206 with adhesives 202. This could be accomplished by machining a transducer 34 such that the ends of the transducer are thicker (or thinner) than the center, as shown in FIG. 19.
 As shown in FIG. 20, another option is to only plate the regions of the transducer 34 where output is desired, or interrupt the plating 122 such that there is no electrical conduction to the mounted ends 214 (conductor wires connected only to the inner plated regions).
 The embodiments described in FIGS. 18-20 can also be combined as necessary to optimize the mounting integrity and transducer performance.
 Cooling Design Configurations: Cooling flow may be necessary to 1) Prevent the transducer temperature from rising to levels that may impair performance, and 2) Prevent the mucosal lining of the sphincter from heating to the point of irreversible damage. The following embodiments describe the various means to meet these requirements.
FIG. 21 shows cooling fluid 82 being passed through a central lumen 53 and out the distal tip 37 to prevent heat buildup in the transducer 34. The central column of fluid 82 serves as a heat sink for the transducer 34.
FIG. 22 is similar to FIG. 21 except that the fluid 82 is recirculated within the central lumen 53 (actually a composition of two or more lumens), and not allowed to pass out the distal tip 37.
FIG. 23 (also shown a part of the preferred embodiment of FIG. 2) shows the fluid circulation path involving the balloon itself. The fluid enters through the balloon inflation lumen 51 and exits through one or more ports 224 in the central lumen 53, and then passes proximally out the central lumen 53. The advantage of this embodiment is that the balloon 46 itself is kept cool, and draws heat away from the mucosal lining of the sphincter. Pressure of the recirculating fluid 82 would have to be controlled within a tolerable range to keep the balloon 46 inflated the desired amount. Conceivably, the central lumen 53 could be the balloon inflation lumen, with the flow reversed with respect to that shown in FIG. 23. Similarly, the flow path does not necessarily require the exit of fluid in the central lumen 53 pass under the transducer 34— fluid 82 could return through a separate lumen located proximal to the transducer.
 In another embodiment (not shown), the balloon could be made from a porous material that allowed the cooling fluid to exit directly through the wall of the balloon. Examples of materials used for the porous balloon include open cell foam, ePTFE, porous urethane or silicone, or a polymeric balloon with laser-drilled holes. It is also conceivable that if a conductive media, such as saline is used for the cooling fluid, and a ground patch attached to the patient, electrical RF energy from the outer plating of the transducer could be allowed to pass into the tissues and out to the ground patch, resulting in a combination of acoustic and RF heating of the tissue.
FIG. 24 shows the encapsulation of the transducer 34 within another lumen 240. This lumen 240 is optionally expandable, formed from a compliant or non-compliant balloon material 242 inside the outer balloon 46 (the lumen for inflating the outer balloon 46 is not shown). This allows a substantial volume of fluid to be recirculated within the lumen 240 without affecting the inflation pressure/shape of the outer balloon 46 in contact with the sphincter. Allowing a substantial inflation of this lumen decreases the heat capacity of the fluid in the balloon in contact with the sphincter and thus allows for more efficient cooling of the mucosal lining. Fluid 82 could also be allowed to exit the distal tip. It can also be imagined that a focusing lens material 170 previously described could be placed on the inner or outer layer of the lumen material 242 surrounding the transducer 34.
 As is shown in FIG. 25, there can be an outer balloon 46 that allows circulation over the top of the inner balloon 242 to ensure rapid cooling at the interface. To ensure flow between the balloons, the inner balloon 242 can be inflated to a diameter less than the outer balloon 46. Flow 82 may be returned proximally or allowed to exit the distal tip. Another version of this embodiment could make use of raised standoffs 250 (not shown) either on the inside of the outer balloon 46 or the outside of the inner balloon 242, or both. The standoffs 250 could be raised bumps or splines. The standoffs 250 could be formed in the balloon material itself, from adhesive, or material placed between the balloons (i.e., plastic or metal mandrels). The standoffs 250 could be arranged longitudinally or circumferentially, or both. While not shown in a figure, it can be imagined that the outer balloon 46 shown in FIG. 25 may only need to encompass one side (i.e., the proximal end) of the inner balloon, allowing sufficient surface area for heat convection away from the primary (inner) balloon 242 that in this case may be in contact with the tissue. In the case of treating Barrett's Esophagus, the space between the two balloons may be filled with an oil suspension or other fluidic or thixotropic medium that has relatively high acoustic attenuation properties. The medium does not necessarily need to recirculate. The intent is that this space between the balloons will preferentially heat and necrose the intestinal metaplasia lining the esophagus.
 In another embodiment, illustrated in FIG. 26, occluding members 260 are positioned proximal (260 a) and distal (260 b) to the transducer element for occluding the sphincter lumen 270. The occluding members 260 may also serve to dilate the sphincter region to a desired level. The occluding members 260 are capable of being expanded from a collapsed position (during catheter delivery) for occlusion. Each occluding member 260 is preferably an inflatable balloon, but could also be a self-expanding disk or foam material, or a wire cage covered in a polymer, or combination thereof. To deploy and withdraw a non-inflatable occluding member, either a self-expanding material could be expanded and compressed when deployed out and back in a sheath, or the occluding member could be housed within a braided or other cage-like material that could be alternatively cinched down or released using a pull mechanism tethered to the proximal end of the catheter 30. It may also be desirable for the occluding members 260 to have a “textured” surface to prevent slippage of the device. For example, adhesive spots could be applied to the outer surface of the balloon, or the self-expanding foam could be fashioned with outer ribs.
 With the occluding members 260 expanded against the sphincter lumen, the chamber 278 formed between the balloons is then filled with a fluid or gel 280 that allows the acoustic energy 35 to couple to the tissue 60. To prevent heat damage to the mucosal lining ML of the tissue lumen 270, the fluid/gel 280 may be chilled and/or recirculated. Thus with cooling, the lesion formed within a target site T the tissue 60 is confined inside the tissue wall and not formed at the inner surface. This cooling/coupling fluid 280 may be routed into and out of the space between the occluding members with single entry and exit port, or with a plurality of ports. The ports can be configured (in number, size, and orientation) such that optimal or selective cooling of the mucosal surface is achieved. Note also that cooling/coupling fluid 280 routed over and/or under the transducer 34 helps keep the transducer cool and help prevent degradation in performance.
 The transducer element(s) 34 may be any of those previously described. Output may be completely circumferential or applied at select regions around the circumference. It is also conceivable that other energy sources would work as well, including RF, microwave, laser, and cryogenic sources.
 In the case where only certain sectors of tissue around the circumference are treated, it may be desirable to utilize another embodiment, shown in FIG. 27, of the above embodiment shown in FIG. 26. In addition to occluding the proximal and distal ends, such a design would use a material 290 to occlude regions of the chamber 278 formed between the distal and proximal occluding members 260. This would, in effect, create separate chambers 279 around the circumference between the distal and proximal occluding members 260, and allow for more controlled or greater degrees of cooling where energy is applied. The material occluding the chamber could be a compliant foam material or an inflatable balloon material attached to the balloon and shaft. The transducer would be designed to be active only where the chamber is not occluded.
 Temperature Monitoring: The temperature at the interface between the tissue and the balloon may be monitored using thermocouples, thermistors, or optical temperature probes. Although any one of these could be used, for the illustration of various configurations below, only thermocouples will be discussed. The following concepts could be employed to measure temperature.
 In one embodiment shown in FIG. 28, one or more splines 302, supporting one or more temperature sensors 52 per spline, run longitudinally over the outside of the balloon 46. On each spline 302 are routed one or more thermocouple conductors (actually a pair of wires) 306. The temperature sensor 52 is formed at the electrical junction formed between each wire pair in the conductor 306. The thermocouple conductor wires 306 could be bonded straight along the spline 302, or they could be wound or braided around the spline 302, or they could be routed through a central lumen in the spline 302.
 At least one thermocouple sensor 52 aligned with the center of the ultrasound beam 35 is desired, but a linear array of thermocouple sensors 52 could also be formed to be sure at least one sensor 52 in the array is measuring the hottest temperature. Software in the generator 70 may be used to calculate and display the hottest and/or coldest temperature in the array. The thermocouple sensor 52 could be inside or flush with the spline 302; however, having the sensor formed in a bulb or prong on the tissue-side of the spline 302 is preferred to ensure it is indented into the tissue. It is also conceivable that a thermocouple placed on a slideable needle could be used to penetrate the tissue and measure the submucosal temperature.
 Each spline 302 is preferably formed from a rigid material for adequate tensile strength, with the sensors 52 attached to it. Each individual spline 302 may also be formed from a braid of wires or fibers, or a braid of the thermocouple conductor wires 306 themselves. The splines 302 preferably have a rectangular cross section, but could also be round or oval in cross section. To facilitate deployment and alignment, the splines 302 may be made out a pre-shaped stainless steel or nitenol metal. One end of the spline 302 would be fixed to the catheter tip 37, while the proximal section would be slideable inside or alongside the catheter shaft 36 to allow it to move with the balloon 46 as the balloon inflates. The user may or may not be required to push the splines 302 (connected to a proximal actuator, not shown) forward to help them expand with the balloon 46.
 The number of longitudinal splines could be anywhere from one to eight. If the transducer 34 output is sectored, the splines 302 ideally align with the active transducer elements.
 In a related embodiment, a braided cage (not shown) could be substituted for the splines 302. The braided cage would be expandable in a manner similar to the splines 302. The braided cage could consist of any or a combination of the following: metal elements for structural integrity (i.e., stainless steel, nitenol), fibers (i.e., Dacron, Kevlar), and thermocouple conductor wires 306. The thermocouple sensors 52 could be bonded to or held within the braid. For integrity of the braid, it may be desirable for the thermocouple conductors 306 to continue distal to the thermocouple junction (sensor) 52. The number structural elements in the braid may be 4 to 24.
 In another embodiment shown in FIG. 29, a design similar to the embodiment above is used, except the distal end of the spline 302 is connected to a compliant band 304 that stretches over the distal end of the balloon as the balloon inflates. The band 304 may be formed out of a low durometer material such as silicone, urethane, and the like. It may also be formed from a wound metal spring. The spline 302 proximal to the balloon may then be fixed within the catheter shaft 36. Of course the arrangement could be reversed with the spline 302 attached to the distal end of the balloon 46, and the compliant band 304 connected to the proximal shaft 36.
 In another embodiment shown in FIG. 30, the sensors 52 are bonded with adhesive 308 to the inside of the balloon (in the path of the ultrasound beam 35). The adhesive 308 used is ideally a compliant material such as silicone or urethane if used with a compliant balloon. It may also be a cyanoacrylate, epoxy, or UV cured adhesive. The end of the conductor wire 306 at the location of the sensor 52 is preferably shaped into a ring or barb or the like to prevent the sensor from pulling out of the adhesive. Multiple sensors 52 may be arranged both circumferentially and longitudinally on the balloon 46 in the region of the ultrasound beam 35. Thermocouple conductor wires 306 would have sufficient slack inside the balloon 46 to expand as the balloon inflates.
 In another embodiment (not shown), the thermocouple conductor wires are routed longitudinally through the middle of the balloon wall inside preformed channels.
 In another embodiment shown in FIG. 31, the thermocouple sensors 52 are bonded to the outside of the balloon 46, with the conductor wires 306 routed through the wall of the balloon 46, in the radial direction, to the inside of the balloon 46 and lumens in the catheter shaft 36. The conductor wires 306 would have sufficient slack inside the balloon to expand as the balloon inflates. To achieve the wire routing, a small hole is punched in the balloon material, the conductor wire routed through, and the hole sealed with adhesive. The conductor wire could be coated in a material that is bondable with the balloon (i.e., the balloon material itself, or a compatible adhesive 308 as described for FIG. 30) prior to adhesive bonding to help ensure a reliable seal.
 In another embodiment shown in FIGS. 32a-32 c, the thermocouple sensors 52 mounted on the outer surface of the balloon (regardless of how the wires 306 are routed) are housed in raised bulbs 310 of adhesive 308 (or a molded section of the balloon material itself) that help ensure they are pushed into the tissue, allowing more accurate tissue temperature measurement that is less susceptible to the temperature gradient created by the fluid in the balloon. For compliant balloons, a stiff exposed sensor 52 could be housed in a bulb of compliant material with a split 312. As the balloon 46 inflates, the split 312 in the bulb 210 opens and exposes the sensor 52 to the tissue. As the balloon 46 deflates, the bulb 310 closes back over the sensor 52 and protects it during catheter manipulation in the body.
 In another embodiment (not shown), an infrared sensor pointed toward the heat zone at the balloon-tissue interface could be configured inside the balloon to record temperatures in a non-contact means.
 For the embodiments described in either FIG. 26 or FIG. 27 above, it may also be desirable to monitor the temperature of the tissue during energy delivery.
 This would be best accomplished through the use of thermocouples aligned with the ultrasound beam emanating from the transducer. Each thermocouple would monitor the temperature of the mucosal surface to ensure that the appropriate amount of power is being delivered. Power can be decreased manually or though a feedback control mechanism to prevent heat damage to the mucosa, or the power can be increased to a predetermined safe mucosal temperature rise to ensure adequate power is being delivered to the submucosa.
 As shown in FIG. 33, the thermocouple sensors 52 could be mounted on splines 302 similar in design, construction, and operation to those described previously. In this configuration, the splines 302 are expanded against the tissue without the use of an interior balloon. They are deployed before, during, or after the occlusion members 260 are expanded. The braided cage configuration described above may also be used.
 In another embodiment (not shown), the splines 302 or braided cage containing the thermocouple sensors 52 could span over the top of either or both expandable occlusive members 260. If the occlusive members 260 are balloons, the balloons act to expand the cage outward and against the tissue. If the occlusive members 206 are made from a self-expanding foam or disk material, the cage can be used to contain the occlusive material 206 during advancement of the catheter by holding the individual components of the cage down against the shaft under tension. Once positioned at the site of interest, the cage can be manually expanded to allow the occlusive members 260 to self-expand.
 The direction of ultrasound delivery to this point has mostly been described as moving radially into the tissues of the esophagus, LES, and/or gastric cardia. Other system embodiments described below may be employed to aid in using an ablation device that delivers energy in a variety of directions into the tissue. For example, the ablation device can be oriented such that the energy is applied through the longitudinal axis of the sphincter wall, as opposed to radially through the wall. This has the advantage of preventing energy from passing through the outer wall where surrounding structures, such as the vagal nerves, liver, aorta, and mediastinum reside. In addition, longitudinal lesions may help reduce the axial compliance of the sphincter, preventing it from shortening and thus delaying how soon it opens as the gastric pressure increases. The designs also lend themselves to use of a planar or partial arc transducer that can be more reliably fabricated into a thinner wall than a cylindrical (for circumferential output) transducer. This allows for operation at higher frequencies that increases energy attenuation in the tissue and limits the depth of penetration of the ultrasound energy. In this instance, radial direction of the energy is more feasible without damage to collateral structures. Finally, particular embodiments of this invention may make lesion formation in the gastric cardia easier than is possible with a circumferential system. Lesions created on the “underside” of the sphincter in the region of the gastric cardia may help reduce the compliance of the gastric sling fibers in this region. This may help delay opening of the sphincter as the stomach expands due to increases in gastric pressure. The region of the gastric cardia may also have more vagal innervation responsible for transient relaxations of the sphincter; the lesions would reduce this innervation.
 As shown in FIG. 34a, the present invention relates to an ablation system 400 consisting of an ablation catheter 32 with an acoustic energy delivery element (ultrasound transducer) 34 mounted on the distal end of the catheter. The device is delivered transorally to the region of the LES 18. The system 400 consists of the following key components:
 1. An overtube 500 having a balloon 502 attached to the distal opening 503.
 2. An endoscope 96 having at least one therapeutic channel 518 greater than 2.8 mm.
 3. A catheter 32 having a shaft 36 and a proximal hub/handle 38 containing fluid ports 40, electrical connectors 42, and optional central guidewire lumen port 44. The catheter also has an ultrasound transducer 34 on a mounting 37 that produces acoustic energy 35 at the distal end of the distal catheter shaft 520
 4. An energy generator 70 and connector cable(s) 72 for driving the transducer and displaying temperature values
 5. A fluid pump 80 delivering cooling fluid 82.
FIG. 34b illustrates a similar system where the ablation catheter 32 makes use of a transducer 34 designed to deliver acoustic energy radially (either circumferentially or in one or more discrete sectors) from the longitudinal axis. The catheter 32 can be moved with respect to the overtube balloon 502. The tip of the catheter may also be deflectable from an actuator on the proximal hub/handle 38.
 While use of the catheter 32 through a channel in the endoscope 96 is preferred, it is conceivable that the catheter 32 could be deployed through the overtube 500 without the use of the endoscope 96.
 The preferred method of ablation treatment is illustrated in FIGS. 35-39. In FIG. 35, an overtube device 500 having a peanut-shaped balloon 502 is preloaded over an endoscope 96. The balloon 502 is preferably made of a compliant material such as silicone or polyurethane, but could also be a material such as polyethylene or PET. The wall thickness of the balloon is preferably thicker in the middle of the “peanut” to limit the degree of radial expansion compared to the proximal and distal sections. Alternatively the middle of the balloon is simply blown or molded to a smaller diameter. The tip of the overtube balloon 502 is fitted with a relatively rigid nipple-shaped dome 504 that allows a snug fit with the tip of the endoscope. The dome 504 may be an integral, thickened portion of the balloon itself, or a separate component that the balloon is bonded to. It is conceivable that to aid seating the endoscope 96 in the dome 504 and make later release more reliable, the tip of the endoscope could be secured to the dome with the aid of one of the available endoscope channels. For instance, suction from a channel of the endoscope 96 could be applied to hold the dome against the endoscope tip, or a screw or barb or other grasping mechanism could be advanced through the channel to secure the dome tip to the tip of the endoscope. Also, vacuum may be applied to the balloon 502 using the lumen of the overtube 500, or from a lumen of the endoscope 96, to fold the balloon 502 down onto the endoscope. The proximal end of the overtube 502 is fitted with appropriate stasis valves to prevent leakage out the proximal end. The balloon 502 and/or the dome 504 should be transparent to allow visualization of tissue structures through the balloon wall.
 An optional embodiment (not shown) would be the use of a vent tube alongside the overtube 500 and overtube balloon 520 to allow air in the stomach to vent out of the patient. The tube could be positioned completely separate from the overtube or advanced through an optional lumen in the overtube, exiting just proximal to the overtube balloon 520. The distal end of the vent tube would be positioned in the stomach 20 distal to the overtube balloon 520. The tube is preferably relatively stiff at the proximal end (for push transmission), and floppy at the distal end so that it is atraumatic and conforms well to the overtube balloon 520 as the balloon entraps the vent tube against the tissue. While the inner diameter of the vent tube needs to be only on the order of 0.005″ to vent air, larger inner diameters up to 0.042″ may be used to speed the aspiration of fluids or allow the passage of a guide wire (for ease in placement). The wall thickness may be 0.003″ to 0.010″, preferably, 0.004″. The wall of the tube may be a solid material, or a composite of plastic and adhesives and/or stainless steel or nitenol wires or Dacron fibers. The wall may consist of stainless steel, nitenol, or a plastic such as polyurethane, pebax, polyethylene, PET, polyimide, or PVC.
 With the endoscope 96 seated in the dome 504 of the balloon 502, the overtube 500 and endoscope 96 are advanced down the esophagus 10 to the region of the LES 18. As illustrated in FIG. 36, using endoscopy visualization, and retracting the endoscope as necessary, the balloon is positioned so that the peanut shape straddles the LES 18.
 The balloon is then inflated with a fluid medium (water, saline, contrast, etc.) as illustrated in FIG. 37. Inflation is performed preferably through the lumen of the overtube, although an available channel in the endoscope 96, or lumens in the ablation catheter 32 may also be used. The shape of the balloon allows it to conform to the contours of the esophagus at, and on either side of, the LES. The shape also helps stabilize the balloon at the LES. The balloon is inflated to a diameter that allows safe dilatation of the folds in the esophagus. The nominal inflated diameter of the proximal section 510 should be 20 mm, with a range of 15-30 mm. The distal section 512 can be larger, nominally 40 mm and a range of 15-50 mm. Diameter may be assessed by fluid volume, pressure, endoscopic visualization, or fluoroscopic visualization. The balloon and the fluid inside form a “coupling chamber” that allows ultrasound energy to be transmitted to the tissue from inside the balloon. Addition of contrast to the fluid allows fluoroscopic visualization of the shape and diameter.
 With the balloon inflated, the distal shaft 520 of the ablation catheter 32 is advanced out of the endoscope channel 518, as shown in FIGS. 38a and 38 b. Mounted on the distal shaft 520 is an ultrasound transducer 34. The transducer 34 is preferably a cylinder with only one segment of the circumference active. Other transducers have been described in provisional patent application 60/393,339 and are incorporated by reference herein. An external manipulation member (hereafter called pull wire) 530 is positioned on the side of the distal shaft 520 opposite the active transducer segment. The distal end of the pull wire 530 is attached to a hinge (or weld-joint) 528 at the catheter tip, and the proximal end is routed through a lumen orifice 532 in the distal catheter shaft 520 and out the proximal end of the catheter to an actuator on the hub/handle 38. As the pull wire 530 is tensioned, a soft, kink resistant section 522 of the distal shaft 520 forms a tight bend that allows the transducer to be oriented at the desired angle inside the balloon 502. Compression of the pull wire straightens the distal shaft 520 and may also bend it in the opposite direction. The endoscope and/or fluoroscope may be used to determine the proper orientation of the transducer relative to the tissue.
 With the transducer 34 oriented towards the tissue, cooling flow circulation is initiated as shown in FIG. 38b, to prevent heating of the mucosa during subsequent energy delivery. Chilled fluid 82 from the pump 80 is preferably routed through a lumen under/behind the transducer, out the distal orifice 526 and back through the proximal (to the transducer) orifice 524 to a separate lumen returning to the pump 80 or other reservoir. Alternatively, or in addition, chilled fluid may be circulated via the overtube lumen or a lumen in the endoscope.
 As shown in FIG. 39, energy from the generator 70 is applied to the transducer 54, which creates a beam of acoustic energy 35 directed towards the LES tissue 18. The transducer frequency, power level, and power duration are chosen to create a lesion 550 a of a desirable size. The catheter 32 may be torqued and the pullwire 530 adjusted to reorient the transducer to another location around the circumference and/or the length of the LES region, where energy delivery and lesion creation are repeated. Ideally, each lesion is formed for about 5-10 mm down the axial length of the LES at a radial depth of 3-8 mm. As shown in FIG. 40, the transducer can also be directed towards the LES 18 from within the stomach 12. Also, from the same position, the transducer can be oriented to ablate the gastric cardia 20, just beyond the LES 18. Lesions in the gastric cardia might be more effective in ablating vagal afferent nerve fibers responsible for transient relaxations of the LES and also reduce the compliance of the gastric sling fibers to delay sphincter opening during gastric distension.
FIG. 41 shows another embodiment of the invention where the transducer 34 is instead (or in addition to) positioned at the tip of the ablation catheter to direct energy in the same direction as the axis of the catheter.
FIG. 42 shows another embodiment where a smaller balloon 502′ is fitted on the tip of the overtube 500 to contain the distal portion of the ablation catheter 32. The distal end of the overtube shaft 500 in this case is aligned with the distal end of the endoscope 96 and may be deflected with the endoscope 96. Also as shown in FIG. 42, the pull wire may be routed through a separate channel of the endoscope (the wire would need to be back-loaded through the endoscope before it is inserted into the overtube).
FIG. 43 shows another embodiment where the balloon 502″ is attached to the distal shaft 520 of the catheter 32, and no overtube is used. The distal end of pull wire 530 may be attached to the outside of the shaft proximal to the balloon, or fixed inside the distal shaft.
FIG. 44 shows another embodiment of the overtube 500 where a distal member 501 extends from the distal opening of the overtube to the distal end of the balloon 502. The distal end of the balloon 502 is bonded to the distal end of the member 501. The member 501 may have one or more lumens to allow passage of a guide wire 400, and for inflation/deflation of the balloon, and/or circulating cooling fluid within the balloon. The distal opening of member 501 may also be used to vent air from the stomach. The endoscope 96 carrying catheter 32 may be advanced through the main channel of the overtube 500 as described previously.
FIG. 45 shows another embodiment of the overtube 500 employing the use of a doughnut shaped balloon 502 e attached to the distal end of the overtube. The doughnut shape allows for a central lumen in the balloon. This may be important to vent air from the stomach 12 or allow passage of the endoscope distal to the balloon. The doughnut shape also provides a good reference to the position of the inferior LES when inflated in the stomach and pulled back against the bottom of the LES.
FIG. 46 illustrates the use of the ablation catheter 32 with the overtube having a doughnut shaped balloon. The distal end of the ablation catheter 32 is advanced through the center of the doughnut shaped balloon 502 e. With the transducer 34 aligned in the desired location, the ablation catheter balloon 46 is inflated inside the overtube balloon 502 e. With both the overtube balloon and 502 e and the ablation catheter balloon 46 filled with an adequate coupling fluid (i.e., water), the ultrasound energy is able to propagate relatively undamped until it reaches the tissue of the LES 18 or gastric cardia 20. The fluid inside either or both the overtube balloon 502 e or the ablation catheter balloon 46 may be recirculated and chilled to prevent overheating of the transducer 34 or the mucosa. Conceivably, the overtube 500 could have a window opening (not shown) proximal to the doughnut shaped balloon 502 e. This would allow the balloon 46 of the ablation catheter to inflate out of the inner lumen of the overtube proximal to the overtube balloon 502 e.
FIG. 47 shows another embodiment where the peanut shaped balloon 502 is mounted on the distal ablation catheter shaft 520, and no overtube is used. The ablation catheter may or may not be passed through an endoscope 96. If not passed through an endoscope, an endoscope is advanced alongside the catheter shaft, or positioned at the desired location and the distance noted before it is removed and the ablation catheter inserted the same distance. Transducers 34 are mounted on the distal shaft 520 under to balloon at locations either or both distal and proximal to the LES 18 (the sunken region of the peanut balloon 502). The transducers may be hinged to the side of the shaft and at point 229, and hinged at the other end 528 where a pull wire is attached. The pull wire 530 is routed through the shaft 520 to an actuator on the proximal end of the device. Push and pull of the pull wire 530 may allow swiveling of the transducer to create lesions 551 a-551 d. The transducers may also be driven simultaneously while angled to focus at an intersection point within the wall of the LES 18.
 Other embodiments focused on a means to change the angle of the transducer are illustrated in FIGS. 48a-48 d. In FIG. 48a, the transducer is mounted on a shaft member 521, which is advanced out of a lumen in the distal shaft 520 of the ablation catheter 32. The shaft 521 may have a set curve or be deflectable with an internal pull wire. It can be seated in a channel 525 in shaft 520 during advancement and retraction. The transducer 34 can be uni- or multidirectional. In FIG. 48b, the shaft 521 continues distal to the transducer where it is fixed inside shaft 520. Pushing and pulling on the proximal shaft 520 causes a prolapse proximal to the transducer at a soft, kink-resistant point 523. In FIG. 48c, pull wire 530 is attached to the proximal end of the transducer at hinge 528. The “pull wire” is pushed forward to increase the transducer angle, and pulled back to reduce the angle. In FIG. 48d, the transducer 34 is angulated by inflating a bladder 527 under the transducer. A floppy tether 529 may be tensioned to fully seat the transducer 34 and bladder 527 into groove 525 during insertion and removal.
 In another embodiment shown in FIG. 49a, an endoscope 96 with two available channels is advanced down the esophagus 10 to the region of the LES 18. The distal shaft 520 of ablation catheter is advanced out of one of the available channels of the endoscope 96 to the region of the LES 18 to be treated. Mounted on the distal shaft 520 is an ultrasound transducer 34. The transducer 34 is preferably mounted to deliver a beam of acoustic energy in the same direction as the catheter's longitudinal axis, but could also be designed to deliver energy at other angles to the axis. The transducer is optionally surrounded distally by a coupling chamber 570, consisting of a rigid or flexible membrane 571 filled with an acoustic coupling medium (e.g., water, saline, gel). The thickness of the membrane 571 where the ultrasound energy passes is preferably less than one-quarter the wavelength of the ultrasound to prevent transmission loss. One or more temperature sensors 569 may be mounted on the tip of the membrane 571 in the path of the ultrasound beam 35 to monitor temperature of the mucosa to prevent overheating.
 An occlusion balloon catheter 560 consisting of a catheter shaft 561 and balloon 562 is advanced through another available channel of the endoscope 96 and distal to the LES 18. The balloon 562 is inflated (with air or water via a lumen in the catheter, exiting at port 563 inside the balloon) in the stomach 12 to a diameter larger than the LES opening and then pulled back against the LES to create a seal. Fluid 565 (e.g., water, saline) is injected through a lumen in catheter 560, exiting from a port 564 proximal to the balloon, to fill the region of the esophagus 10 proximal to the LES 18. This provides a means of ensuring acoustic energy is coupled to the tissue as well as providing a means of cooling the mucosa to prevent heat damage. The fluid 565 may alternatively or additionally be infused through a lumen in the endoscope 96. Circulation of the fluid 565 may also be accomplished through multiple lumens in shaft 561 of catheter 560, or endoscope 96.
 As shown in FIG. 49b, an overtube 500 having a balloon 572 bonded to the distal portion of the overtube shaft may be used to create a proximal seal to contain the fluid 565 infused in the region of the LES 18 (the balloon catheter 560 would continue to be used to contain the fluid 565 at the distal portion of the LES 18). As illustrated in FIG. 49b and FIGS. 49c-e, a stasis valve 573 on the tip of the overtube may be used to prevent fluid from migrating up the space between the endoscope and overtube, as well as to prevent scraping the mucosa when the overtube is moved relative to the endoscope. The valve 573 is compressible (formed from silicone rubber or polyurethane) to accommodate a range of endoscope outer diameters. The proximal end of overtube 500 may be fitted with a similar stasis valve, or o-ring 574 which may be manually compressed by turning a threaded nut 575. A side port luer 576 may be used to flush the lumen of the overtube 500.
 Referring back to FIG. 49a, once the fluid 565 is infused, the transducer 34 is energized to deliver ultrasound energy 35 to the region of the LES 18. The energy 35 is delivered for a sufficient time and energy to create a lesion 575 a in the tissue in the region of the LES 18. The process may be repeated multiple times around the cicumference and/or axis of the LES 18 to create additional lesions, such as 575 b.
 In another embodiment shown in FIG. 50, the ablation catheter 32 is configured similar to that shown in FIG. 51. The catheter 32 is designed to be preloaded in the endoscope 96 such that an extended portion of the shaft 572 distal to the transducer 34 runs from the distal endoscope, out through the proximal end. This allows manipulation of two shaft elements, 570 and 572, proximal and distal to the transducer, respectively, to change the orientation of the transducer 34. The transducer 34 in this configuration is elongated such that its width is approximately the same as the diameter of the catheter shaft, and the length is in the range of 3-10 mm. An occlusion balloon catheter 560 is again positioned distal to the LES, but runs alongside the endoscope 96, not through it. An overtube 500 with balloon 572 may be used in a manner similar to that of FIG. 49b. As described for FIGS. 49a and 49 b, fluid 565 is infused into the region of the LES 18 and acoustic energy 35 is delivered from the transducer 34 into the tissue to form lesions in various locations such as 576 a and 576 b.
 In another embodiment shown in FIG. 51, the distal shaft 520 of ablation catheter 32 is advanced out of an endoscope 96 in the region of the LES 18. In this embodiment, the endoscope only requires one free channel, that dedicated to the ablation catheter 32. The distal shaft 520 of the catheter 32 is fitted with a transducer 34, mounted along the side of the of the catheter shaft. The transducer is surrounded by a membrane 580 with features and function similar to that described for FIG. 49a to aid in coupling of the ultrasound energy to the tissue. The fluid or gel in the membrane may be recirculated to keep the transducer and mucosa cool. Mounted to the opposite side of the shaft 520 from the transducer 34 is an expandable member 582 designed to force the membrane 580 surrounding the transducer 34 securely against the tissue. The expandable member 582 is preferably a balloon, but could also consist of one or more moveable splines designed to bow against the tissue. An internal pull wire mechanism (not shown) connected to a proximal actuator could also be employed to aid in deflecting the distal shaft 520 against the tissue in the region of the LES 18. Once in position against the tissue, ultrasound energy 35 is delivered from the transducer 34 to form lesions in various positions in proximity to the LES, such as 577 a and 577 b.
 In another embodiment shown in FIG. 52a and FIG. 52b, an ablation catheter 32 is advanced to the region of the LES. Accurate positioning at the LES is accomplished by using markings on the shaft corresponding to previous use of an endoscope, or placing an endoscope alongside the shaft of the ablation catheter. Constructed on the distal end of catheter shaft 520 is a tissue chamber 590 designed to accept a portion of the muscle wall in the region of the LES 18. The tissue chamber may measure 5-25 mm long and 3-10 mm deep. Constructed proximal to the tissue chamber 590 is a transducer assembly chamber 592. Within chamber 592 a transducer assembly 594 is slideable via a piston 596 connected to an actuator on the proximal end of the catheter 32. The transducer assembly 594 consists of a transducer 34 mounted with proximal air backing and a distal coupling chamber 598 formed by a membrane 599 (similar in form and function to that described for FIG. 49). Cooling fluid 600 may be circulated in and out of the chamber 598. Using the piston 596 the assembly may be pushed down onto the tissue drawn into the tissue chamber 590. To aid in drawing the tissue into the chamber 590 and securing it there, suction from a plurality ports 601 may be employed. The use on an expandable member 602 (balloon or splines) mounted opposite to the chamber may aid in forcing the catheter into the tissue (and thus the tissue into the chamber 590).
 At the distal end of the chamber is an optional chamber 604 that may also accept circulated cooling fluid 600 to keep the distal end of the mucosa from overheating. Distal to optional chamber 604 is an element 606 that can be configured to absorb ultrasound energy not absorbed by the tissue. This may consist of a highly attenuating material such as silicone or polyurethane rubber. Alternatively, element 606 could be another transducer 34 that directs energy into the tissue towards that coming from the transducer assembly 594 to increase the heating within the tissue. An atraumatic tip 608 is attached to the distal tip of the catheter 32. Once the tissue is pulled into the coupling chamber 590, the transducer assembly 594 pushed against the tissue and infused with cooling fluid 600, ultrasound energy 35 is delivered into the tissue to form a lesion 610.
 An alternative embodiment of the device described in FIG. 52 would be to not require the transducer assembly 594 to be moveable, and thereby eliminate the need for the piston 596. The push force onto the tissue could be accomplished by designing the membrane 599 to be outward expandable. Also, an internal pull wire mechanism (not shown) attached to the distal tip of the catheter and connected to a proximal actuator could also be employed to aid in deflecting the distal shaft 520 against the tissue in the region of the LES 18. More specifically, the pull wire may be used to curl the distal tip 608 (and attached segments 606 and 604 under and against the LES tissue.
 Other means may be used in addition to or in place of that described for FIG. 52 to draw the tissue into the tissue chamber. FIG. 53a illustrates grasping mechanisms 620 actuated by pull wires 622 connected to an actuator at the proximal end of catheter 32. The grasping mechanisms 620 are formed from a metal or hard plastic and contain frictional tread 624 to assist in holding the slippery tissue. They are also contained within the chamber 590 and hollow in the middle so as to not interfere with the ultrasound energy. The grasping mechanisms 630 illustrated in FIG. 53b are similar to FIG. 53a except that they swing out from the catheter shaft to help pull more tissue into the chamber 590. Additional tread 632 on the bottom (distal) end of the chamber would aid in holding the tissue in place. FIG. 53c shows preformed wire (i.e., stainless steel or nitenol) being advanced out of the catheter shaft to pinch the tissue and help force it into the tissue chamber 590. In FIG. 53d, two “partial doughnut” balloons are inflated to help pinch and push the tissue into the tissue chamber.
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|U.S. Classification||600/459, 600/462|
|International Classification||A61N7/02, A61N7/00, A61B17/00|
|Cooperative Classification||A61B8/4281, A61N2007/0078, A61B2017/0046, A61N2007/0095, A61N7/02, A61B18/20, A61B18/1492, A61B18/1815, A61B18/18, A61N2007/003, A61N2007/0043, A61N2007/0065, A61N2007/0082, A61B17/2202, A61N7/022, A61N2007/0091|
|Feb 28, 2013||AS||Assignment|
Owner name: RECOR MEDICAL, INC., CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:SCHAER, ALAN;REEL/FRAME:029898/0126
Effective date: 20120529