Abstract:
A method and apparatus for treating uterine tissue with ultrasound energy. The method manipulates the position of the patient&#39;s uterus to decrease its distance from an ultrasound therapy transducer while simultaneously engaging a partially filled bladder such that the bladder is compressed to force any bowel tissue out of an acoustic window between the patient&#39;s abdominal wall and uterus. Ultrasound energy is then applied to the uterine tissue.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims the benefit under 35 U.S.C. Section 119(e) of U.S. Provisional Application 61/138,400, filed Dec. 17, 2008, which is herein incorporated by reference in its entirety. 
    
    
     BACKGROUND 
     High intensity focused ultrasound (HIFU) can be used to treat various pathologies within the uterus. HIFU ablation of fibroids and adenomyosis have been reported, and various additional procedures may also be amenable to HIFU treatment, including endometrial ablation, ablation of polyps, et al. 
     When HIFU is applied transabdominally, it is important to ensure that the patient&#39;s bowel does not intervene in the beam path. Otherwise, the gas that is naturally present in bowel will tend to reflect the HIFU, resulting in reduced treatment efficacy and/or dangerous burns of the bowel tissue. If transabdominal imaging ultrasound is used to guide the HIFU treatment, bowel gas will tend to block its transmission as well, resulting in poor quality images of the uterus. The anatomical aperture through which ultrasound may pass safely and unimpeded by the bowel is herein termed the “acoustic window”. 
     In addition, the target uterine tissue must remain within a treatable depth range, i.e. at a depth below the skin surface that is within the focal range of the HIFU and/or imaging transducers (which are typically limited by practical design considerations). 
     In an attempt to increase the acoustic window, users of commercially-available HIFU systems have reported catheterizing the patient&#39;s bladder and filling it with fluid to help displace bowel laterally away from the HIFU beam path. In doing so, the acoustic window becomes defined largely by the lateral dimensions of the bladder. Ultrasound is readily transmitted through the bladder (i.e. since the fluid is relatively transparent to ultrasound), but not through the surrounding bowel. 
     Yet as the bladder fills and expands laterally, it also tends to expand posteriorly away from the abdominal wall. This pushes the underlying uterus in the posterior direction as well, since the bowel and rectum behind the uterus tend to be easily compressed. As the uterus is pressed deeper by the filling bladder, it may eventually move out of range of the abdominally-placed ultrasound or HIFU transducer. Thus, filling the bladder can actually be counter-productive when used as a standalone technique for enlarging the acoustic window. 
     Furthermore, as the bladder fills, it assumes a more spherical shape and becomes less pliable. This results in a decreased contact area at the interfaces of the bladder-uterus and bladder-abdominal wall, allowing loops of bowel to slip in between these interfaces from the periphery. 
     Given these problems, there is a need for a technique that can reliably increase the size of the acoustic window by displacing the bowel from the intended beam path, while minimizing the required focal depth to reach uterine target tissue. 
     SUMMARY 
     Uterine manipulation is frequently performed to facilitate surgical intervention via open laparotomy or laparoscopy. Similarly, filling of the bladder is known to facilitate transabdominal ultrasound imaging, and has also been used to enlarge the acoustic window for HIFU treatment. The technology disclosed herein combines these techniques for the purposes of facilitating transabdominal ultrasound therapy or imaging. In one embodiment, transabdominal ultrasound is applied to the uterus for imaging and/or therapeutic purposes with the bladder at least partially filled and the uterus manipulated anteriorly such that it compresses and spreads the partially-filled bladder laterally in relation to the abdominal wall. The unexpectedly synergistic effect is to simultaneously enlarge the acoustic window AND reduce the depth of target uterine tissue—two highly desirable endpoints that have traditionally been considered to be at odds with one another. 
     In one preferred embodiment, the disclosed technology is uniquely suited to enable hand-guided HIFU treatment of uterine fibroids or other uterine pathologies in a cost-effective and convenient office setting. 
     In another embodiment a HIFU treatment system includes a control system that is programmed to change an amount of fluid that fills a bladder and/or to manipulate a patient&#39;s uterus in an anterior or posterior direction such that the size of the acoustic window is increased in order to deliver HIFU energy to a treatment area with the uterus. 
     In yet another embodiment, a number of uterine manipulators are disclosed that are made of materials that are designed to selectively absorb or reflect HIFU energy or to be transparent to HIFU energy. 
     This summary has introduced a few concepts in simplified form, but is not intended to identify all essential features or scope of the claimed subject matter. Certain aspects and advantages of one or more embodiments may be more readily appreciated by reference to the following description and drawings, which should be considered illustrative and not restrictive with regard to scope of the technology or claims. 
    
    
     
       DESCRIPTION OF THE DRAWINGS 
       The foregoing aspects and many of the attendant advantages of this invention will become more readily appreciated as the same become better understood by reference to the following detailed description, when taken in conjunction with the accompanying drawings, wherein: 
         FIG. 1A  illustrates a patient with an empty bladder and how a bowel section can be situated in the acoustic path between the abdomen and the uterus. 
         FIG. 1B  illustrates a known technique for improving transabdominal ultrasound imaging, in which the bladder is filled to push the bowel laterally out of the acoustic path between the ultrasound transducer (placed on abdominal skin) and the underlying uterus. 
         FIG. 2  shows one embodiment of the disclosed technology in which a uterine manipulator is inserted transcervically to press the uterus anteriorly into a partially filled bladder, thereby optimizing both the shape and size of the bladder. 
         FIGS. 3A and 3B  are sagittal and frontal views of an acoustic window created with one particular embodiment of the disclosed technology. 
         FIGS. 4A and 4B  are laparoscopic photos that illustrate how elevation of the uterus allows it to push into the bladder, causing the latter to spread laterally and conform closely to the uterine surface. 
         FIG. 5  illustrates a system for automatically controlling fluid delivered to or removed from a bladder and the position of a uterus to increase the size of the acoustic window in accordance with an embodiment of the disclosed technology. 
         FIGS. 6A-6C  illustrate uterine manipulators in accordance with embodiments of the disclosed technology. 
     
    
    
     DETAILED DESCRIPTION 
     For purposes of this disclosure, the term “uterine tissue” should be considered to include any normal or pathological tissue within or connected to the uterus, including but not limited to myometrium, endometrium, cervix, serosa, fibroids, adenomyosis, polyps, et. al. The term “bowel” is meant to include small and large intestines. The term “HIFU” stands for “high intensity focused ultrasound”, but should be considered interchangeable herein with the term “therapeutic ultrasound” (which is not necessarily focused). “Acoustic window” refers to the lateral dimensions of the path between the abdominal skin surface and the underlying uterus that is substantially free of obstacles to ultrasound transmission (including but not limited to the bowel). “Transabdominal” refers to the application of ultrasound from a probe placed on the skin of the abdomen. “Digital manipulation” refers to use of one or more fingers inserted transvaginally or transrectally to manipulate the position of the uterus or cervix. 
       FIG. 1A  illustrates a problem that the disclosed technology is designed to address. A patient requiring the application of HIFU to a target area in a uterus  20  has an empty or nearly empty bladder  24 . Because the internal organs in the abdomen and pelvic cavity are soft and movable, portions of the patient&#39;s bowel  26  can move into the area between the abdomen  28 , where a HIFU transducer will be placed, and the target area of the uterus  20 . As indicated above, gas in the bowel can reflect HIFU energy in a manner that limits the treatment of the uterus and can cause potential burning of the bowel. 
       FIG. 1B  illustrates one conventional technique for improving transabdominal ultrasound imaging, in which the bladder  24  is naturally or artificially filled to push the bowel tissue  26  laterally out of the path between an ultrasound probe (not shown but would be placed on the abdominal skin) and the uterus  20 . The bowel  26  typically contains gas which is highly reflective, and thus its presence in the ultrasound path can reduce imaging quality of the underlying uterus. In contrast, fluid in the bladder  24  is relatively transparent to ultrasound. However, this known technique comes with an undesirable side effect, i.e. as the bladder fills, the bladder expands posteriorly away from the abdomen  28  (as well as laterally), which pushes the uterus farther from the ultrasound probe and thereby tends to degrade image quality. Uterine depth is even more critical for HIFU treatment, given the practical limitations on HIFU focal range, which may prevent the ability to treat beyond a certain depth. 
       FIG. 2  shows one embodiment of the disclosed technology in which a uterine manipulator  30  is inserted transcervically and manipulated to press the uterus  20  anteriorly into a partially filled bladder  24 , thereby optimizing both the shape and size of the bladder  24 . The bladder  24  is partially filled either naturally with urine or artificially by filling the bladder with saline or other liquid via a catheter. In some embodiments, a pressure monitor may be used to control an amount of liquid added to or removed from the bladder to maintain it at a desired level of fill. With the bladder  24  partially filled, the bladder is able to be compressed like a thick pancake by the uterus  20  that is moved with the uterine manipulator  30 . The anterior compression of the uterus toward the abdominal wall causes the bladder to push any bowel tissue out of the way and increases the lateral width of the acoustic window, while simultaneously reducing the required focal depth to reach target tissue within the uterus  20 . 
       FIGS. 3A and 3B  provides alternate sketches of the techniques disclosed herein, including sagittal and frontal views. The sagittal view shown in  FIG. 3A  illustrates how a patient&#39;s bowel  26  is moved laterally out of the way by the anterior compression of the uterus  20  into the partially filled bladder  24 . As the bladder  24  is compressed, an acoustic window  35  created between the HIFU applicator  33  and a target treatment area in the uterus is free from bowel tissue. The frontal view shown in  FIG. 3B  illustrates how the uterus  20  is located directly posterior to the bladder  24 , allowing the latter displace any bowel tissue that may be present between the HIFU applicator and the desired treatment area in the uterus. 
       FIGS. 4A and 4B  are laparoscopic photos to illustrate certain aspects of the disclosed technology. In the photo of  FIG. 4B , the uterus is not manipulated and is not in contact with the overlying bladder. In the photo of  FIG. 4A , a uterine manipulator (not shown) is used to elevate the uterus anteriorly into the bladder, causing the relatively pliable partially-filled bladder to conform to the anterior surface of the uterus. Although not shown in these photos, surrounding bowel would be pushed away by the resulting lateral expansion of the bladder. 
     One embodiment of the disclosed technology employs a transcervical element (solid or with hollow cannula for injecting fluid), with or without an atraumatic lip or lever arm that fits around or posterior to the cervix (e.g. in the posterior vaginal fomix) to aid in elevating the uterus. Such a design may eliminate the need for either an intracavitary element (which could interfere with HIFU transmission) or a tenaculum (which may cause pain and/or bleeding). 
     Alternatively, manipulation could be achieved via more conventional instruments which typically include some combination of: a transcervical element or cone, a cannula for injecting fluid into cavity, an intracavitary balloon, an articulating mechanism, and/or a tenaculum to help hold the transcervical element in position. 
     Such instrumentation may also be designed to lock the uterus in a desired position, thereby freeing the physician&#39;s hands for other purposes. 
     If transvaginal instrumentation is used to manipulate the uterus, it may or may not penetrate the cervical os. If it does so (e.g. a transcervical uterine manipulator), the instrumentation may or may not have a retaining balloon, which inflates inside the uterine cavity or cervical canal. The instrumentation may also have one or more portions (which may include a retaining balloon if present) that are specifically designed to reflect ultrasound energy, so as to facilitate visualization of its position during ultrasound imaging, serve as a point reflective source for time reversal correction of HIFU beam aberration, or aid in controlling HIFU effects in surrounding tissue. As will be explained in further detail below, the instrumentation may have one or more portions that are specifically designed to absorb ultrasound energy, so as to enhance the deposition of HIFU energy in surrounding tissue. Alternatively, the instrumentation may be designed with portions that are relatively transparent to ultrasound energy, so as to avoid affecting HIFU or ultrasound imaging. 
     In one embodiment, the instrumentation can have a retaining balloon that conforms to the uterine cavity and selectively absorbs HIFU energy to aid in ablating the endometrial lining. Such instrumentation may also be designed to be compatible with the use of MRI imaging (i.e. non-ferrous components), and could also be designed to enhance the instrumentation&#39;s visibility on MRI imaging. Such instrumentation (or attached balloons) may also include one or more temperature sensors to monitor surrounding tissue temperatures during HIFU treatment. 
     If transvaginal instrumentation is used to manipulate the uterus, it may also include a port for injecting fluid or gas into the uterine cavity and/or cervical canal. As a preferred embodiment, injection of a small amount of saline solution could be used if necessary to aid in visualization of the uterine cavity, e.g. to aid in targeting the endometrial lining and/or fibroids. However, such fluid or gas could also include compounds, particles or bubbles which reflect ultrasound, so as to facilitate visualization of the uterine cavity on ultrasound imaging and/or aid in controlling HIFU effects in surrounding tissue. Alternatively, such fluid or gas may include compounds, particles or bubbles which absorb ultrasound, so as to enhance the deposition of HIFU energy in surrounding tissue (including but not limited to the endometrial lining). 
     The uterus may be manipulated once at the beginning of a procedure, or its position may be adjusted intermittently or continually to aid in targeting of the ultrasound. This repositioning may be performed manually or automatically in response to various parameters. 
     In addition to upward pressure exerted on the uterus, counter compression may also be applied to the ultrasound applicator (on abdominal skin surface) to assist in optimizing the acoustic window and target tissue depth. 
     These techniques disclosed are preferably practiced with patient in a supine or seated position, with or without inclination of the torso to aid in shifting intestines out of the acoustic window. Such positions facilitate the use of HIFU to treat the uterus in a convenient low-cost office setting, since most gynecology offices already have examining tables which can accommodate such positions. However, the disclosed techniques may also be practiced with patient in prone or other positions. 
     In one embodiment, the bladder fill volume is chosen such that bladder can be compressed to minimal dimensions in the anterior-posterior direction, while maximizing its dimensions in the caudal-cephalic and side to side directions. The volume should also be kept low enough to maintain bladder pliability, so as to maximize the contact area between posterior abdominal wall and anterior bladder, and between posterior bladder and anterior uterus. This will exclude any intervening bowel between these surfaces and thus maximize the lateral dimensions of the acoustic window. 
     Bladder fill may be accomplished by a variety of techniques, including having patient arrive with a partially full bladder. If bladder is too full upon arrival, patient may void a measured amount, repeating this procedure until bladder reaches the desired size and degree of pliability. Alternatively, a catheter may be inserted into the bladder via the urethra to allow one-time or periodic addition or extraction of fluid from the bladder. In one embodiment, ongoing control of bladder volume may be accomplished via an indwelling catheter (with or without a retaining balloon). 
       FIG. 5  is a block diagram of a system for automatically controlling the fill of a bladder and the position of the uterus to optimize the acoustic window and treat the uterus with HIFU in accordance with the disclosed technology. In the embodiment shown, a HIFU controller  40  has hardware adapted to deliver HIFU energy though a HIFU transducer  33  to the patient. Images of the tissue being treated can be obtained either through imaging transducer elements on the HIFU transducer  33  or from a separate imaging transducer  56 . The images of the tissue are displayed on a conventional ultrasound monitor  42 . 
     The HIFU controller  40  controls the acoustic window through which HIFU energy is delivered to a uterus by selectively adding liquid to, or removing liquid from the patient&#39;s bladder  24 . In the embodiment shown, the HIFU controller  40  controls a pump  44  that delivers liquid from a liquid source  46  into a catheter that is inserted into the bladder. The catheter can include a pressure sensor that produces signals read by a processor in the controller to monitor the liquid pressure in the bladder. To remove liquid from the bladder, the processor within controller  40  directs a valve  48  to be opened to allow liquid to drain from the bladder or closed to seal the liquid in the bladder. A uterine manipulator  30  is engaged with the uterus  20  and manipulated by a hydraulic piston, pneumatic cylinder, motor or a similar mechanism that controls the manipulator to move the uterus either in the anterior direction towards the bladder or in the posterior direction away from the bladder. As will be appreciated, movement towards the bladder compresses the bladder and pushes any bowel tissue out of the acoustic window  35 . By adjusting the position of the uterus and the filling of the bladder, the HIFU controller  40  operates to remove bowel tissue from the acoustic window and reduces the depth required for the HIFU transducer  33  to treat the uterus  20 . Note that, as an alternative to the uterine manipulator shown, the anterior/posterior position of the uterus with respect to HIFU applicator  33  could be adjusted by other methods including but not limited to: controlling the pressure on or vertical position of the applicator, or controlling the inflation of a rectal balloon. 
     In one embodiment, a processor within the controller  40  is programmed to analyze images obtained of the acoustic window. Any bright reflections around the periphery of the acoustic window or other reflections that may indicate that bowel tissue is in the acoustic window are detected. The HIFU controller  40  then adjusts either or both of the filling of the bladder and movement of the uterine manipulator to remove the source of reflections from the acoustic window. Continuous or intermittent control could be performed manually or automatically. The system can also set bladder fill volume in response to factors which might include (but are not limited to): position of and/or downward pressure exerted on the transabdominal applicator, position of and/or upward pressure exerted on the uterus, pressure within bladder, and location of target tissue relative to the ultrasound applicator. 
     In some cases, the uterus may be large enough to make direct contact with the abdominal wall everywhere within the intended HIFU beam path. In this case, there is no need to interpose the bladder, since direct contact would necessarily exclude the possibility of intervening bowel. To aid in establishing or maintaining a sufficiently large area of direct contact, the ultrasound applicator can be pressed down against the abdominal wall, and/or the uterus can be manipulated upward toward the abdominal wall. 
     In an alternative embodiment of the disclosed technology, manipulation of the uterus can be performed by a variety of techniques including digits (fingers) inserted transvaginally or transrectally, instruments placed in vaginal fornices or on the cervix and/or a transrectal instrument, enema or balloon. The techniques described herein will typically require only simple elevation of the uterus in an anterior direction (as opposed to surgical procedures which may require ability to manipulate the uterus more robustly and/or in multiple directions). Thus, the design of instrumentation to manipulate the uterus can be improved to be less traumatic or painful, thus minimizing the need for anesthesia during its insertion, manipulation or removal. 
       FIGS. 6A-6C  illustrate a number of alternative embodiments of a uterine manipulator that are useful with the disclosed technology. In the embodiment shown in  FIG. 6A , a uterine manipulator is designed to be substantially transparent to an applied HIFU beam. For example, if a patient has a uterine fibroid that is located on the backside (posterior) of the uterus, it is desirable that the uterine manipulator that is used to move the uterus does not impede the delivery of HIFU energy to the fibroid. As shown, a uterine manipulator  100  includes an outer sleeve  102  and an inner shaft  106  that can be advanced or retracted with respect to the outer sleeve. The distal end of the inner shaft  106  may include one or more ports  108  that are used for the delivery or extraction of fluids from the uterine cavity. Such fluids may aid visualization of the uterus during ultrasound imaging, or may be intended to cool the uterus or otherwise interact with HIFU to affect treatment of surrounding tissue, or may contain drugs to directly treat the uterine tissue. The ports  108  are in fluid communication with a fluid lumen (not shown) within the inner shaft that terminates at a fluid port  110 . The distal end of the inner shaft may also include one or more sensors such as pressure sensors or temperature sensors produce signals that can be detected to inform the physician of conditions that are occurring in the uterus during treatment 
     At the proximal end of the inner shaft  106  is a handle that includes controls to selectively tighten or relax controls wires within the inner shaft  106 . The control wires are secured at their distal end to the distal end of the inner shaft such that tension on the controls wires cause the distal end of the shaft to bend in a desired direction in manner similar to a steerable catheter or endoscope. The inner shaft preferably includes an articulation joint near its distal end to aid in bending under tension of the control wires. Depending on the number of control wires and the configuration of the articulation joint, the distal tip of the inner shaft  106  can move in two or more directions. A flange  103  made of a biocompatible material (rubber etc.) is positioned at the distal end of the outer sleeve  102 . During use, the flange  103  is engaged with the opening of the cervix and serves to aid in controlling uterine position as well as sealing the uterus to keep in any liquids. 
     The distal end of the inner shaft  106  is at least partially made of materials that are substantially transparent to HIFU energy. Such materials tend to match the acoustic impedance of the uterine tissue and have low acoustic attenuation with no specular or Rayleigh scatterers. Exemplary materials that exhibit good transparency to HIFU energy include cis-1,4 polybutadiene with ˜0.5% peroxide linker available from Lanxess Corp., TPX (Polymethylpentene Copolymer) available from Mitsui Chemicals America; RTV-616 and RTV-630 (unloaded) available from Momentive Performance Materials (formerly GE Silicones); Castall U-2941 (Urethane; now relabeled as Circalok 6414) available from Lord Corp. In some cases a stiffening member, such as a stainless steel rod, may be included in the distal tip of the inner shaft to provide sufficient strength such that movement of the distal tip with the control wires can move and hold the uterus in the desired position. The stiffening member may be coupled to a heat sink or in thermal contact with liquids delivered from the ports  108  (or other cooling channels in the shaft) to prevent the rod from becoming excessively hot as HIFU energy is applied. 
     In some cases, it is desirable to thermally treat the endometrial lining of the uterus with heat caused by the application of HIFU. In this case, the uterine manipulator of the type shown in  FIG. 6B  can be used. In this embodiment, a uterine manipulator is at least partially constructed of material that is highly absorptive of HIFU. Absorptive materials have a good match to the acoustic impedance of tissue, yet high acoustic attenuation of HIFU and contain only low to moderate Rayleigh scatterers. Examples of such materials include but are not limited to Engage™ (Polyolefin Elastomer) available from Dow Chemical Co.; Surlyn™ (Thermoplastic Ionomer) available from DuPont; Santoprene™ (Thermoplastic Elastomer) available from ExxonMobil Chemical; RTV 560, 615, 630 with 5-10% by weight 25-50 μm borosilicate micro balloon available from Momentive Performance Materials (formerly GE Silicones). It may also be desirable to increase thermal conductivity by adding 5-15% by weight Al203, W03 aluminum nitride and/or diamond powder. 
     In the embodiment shown in  FIG. 6B , a uterine manipulator  150  has an outer sleeve  152  with a conical flange  153  at the distal end thereof that operates to stabilize the manipulator in relation to the uterus and to seal any liquids that may be delivered into the uterus. An inner shaft  160  is movable with respect to the outer sleeve  152  such that it can be inserted into or removed from the uterine cavity to a desired degree while the flange is engaged to the uterus. The inner shaft  160  may include one or more ports from which a liquid can be delivered to or withdraw from the uterus. In some embodiments, the inner shaft  160  may include a handle  166  with controls for manipulating controls wires as described above. In this embodiment, the distal end of the inner shaft  160  includes a balloon  170  that is made of, or coated with, absorptive materials of the type described above. When inflated with a liquid or gas, the balloon  170  engages and conforms to the endometrial wall of the uterus. The application of HIFU energy when the balloon  170  is deployed causes the balloon to become heated in order to thermally treat the lining of the uterus. 
     In an alternative embodiment, the balloon  170  can be coated with, or made from, a material that is reflective of HIFU energy in order to reflect HIFU energy away from the center of the uterus. Examples of such reflective materials include stainless steel, aluminum, titanium or alumina To improve biocompatibility, it may be desirable to coat these materials with a thin jacket of a biocompatible material such as TPX or Santoprene. 
     In an alternative embodiment, the balloon itself may not be absorptive or reflective, but may be filled with fluid which is absorptive or reflective. 
       FIG. 6C  illustrates yet another embodiment of a uterine manipulator. In this embodiment, a uterine manipulator  200  includes an outer shaft  202  with a conical flange  204  at the distal end. An inner shaft  210  is movable with respect to the outer shaft  202  such that a distal end of the inner shaft can be selectively inserted into and removed from a uterus. In this embodiment, the inner shaft has a number of support splines  220  that expand radially outwards when the inner shaft is pushed out of the distal end of the outer shaft  202 . The support splines  220  support one or more sheets  224  of material that is absorptive or reflective of HIFU energy and are shaped to substantially fill the uterus when the support splines  220  are extended. In this embodiment, the support splines are sufficiently stiff such that force on the more proximal portions of the inner shaft  210  or the outer sleeve  202  can move and manipulate the position of the uterus. 
     With the one or more sheets of absorptive or reflective material deployed in the uterus, the application of HIFU energy will cause the sheets to heat or to reflect HIFU energy. 
     While illustrative embodiments have been illustrated and described, it will be appreciated that various changes can be made therein without departing from the scope of the invention. Those of ordinary skill in the art will understand that other embodiments fall within the scope of the description and the claims.