Abstract:
In one aspect, the present disclosure is directed to a method for treating a bladder within a body of a subject, including inserting one or more heaters into the bladder wall of a subject, and selectively heating the one or more heaters by a remote device.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
       [0001]    This application claims the benefit of U.S. Provisional Application No. 61/906,246, filed Nov. 19, 2013, the disclosure of which is incorporated herein by reference in its entirety. 
     
    
     FIELD OF THE DISCLOSURE 
       [0002]    The disclosure relates generally to targeted tissue heating methods and associated systems. 
       BACKGROUND 
       [0003]    Overactive Bladder or OAB is one of the factors that can result in urinary incontinence conditions. OAB is a chronic urological condition characterized broadly as the involuntary and uncontrollable urge felt by a subject to relieve the bladder, leading to abnormally high urinating frequency. Such conditions may occur due to frequent and spontaneous contractions of the detrusor muscle of the pelvic region of a subject. Overactive bladders often exhibit localized changes in detrusor morphology, likely originating from defects on cellular and multicellular level. Such cell related deviations may be attributed to local pathological changes in the muscle condition or topology that may contribute to anomalies in the functionality of the detrusor muscle on a macroscopic scale. 
         [0004]    Current OAB directed therapies include medication, diet modification, programs in bladder training, electrical stimulation, and surgery. However, existing solutions for OAB, fail to properly address local and anatomical abnormalities of the detrusor muscle, thereby indicating the need for alternative therapies for local bladder abnormalities. 
       SUMMARY 
       [0005]    In one aspect, the present disclosure is directed to a method for treating a bladder within a body of a subject, including inserting one or more heaters into the bladder wall of a subject, and selectively heating the one or more heaters by a remote device. 
         [0006]    In yet another aspect, the present disclosure is directed to a method for treating overactive bladder of a subject, including selectively applying heat to the bladder by heating a plurality of heaters implanted in the bladder wall, and the heat being maintained for a desired time period. 
         [0007]    In a further aspect, the present disclosure is directed to a method for treating overactive bladder of a subject, including selectively applying heat to the bladder by heating a plurality of heaters simultaneously, the heaters being implanted in the bladder wall at a depth in the bladder wall sufficient to affect the detrusor muscle of the bladder. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0008]    The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the present disclosure and together with the description, serve to explain principles of the disclosure. 
           [0009]      FIG. 1  is a schematic view of an exemplary targeted tissue heating system in accordance with principles of the present disclosure; 
           [0010]      FIG. 2  is a schematic view of an exemplary delivery device of the tissue heating system of  FIG. 1 ; 
           [0011]      FIG. 3  shows the use of the tissue heating system of  FIG. 1  according to one embodiment; 
           [0012]      FIG. 4  shows the use of the tissue heating system according to another embodiment of the present disclosure; 
           [0013]      FIG. 5  illustrates additional exemplary features of the tissue heating system of  FIG. 1 ; and 
           [0014]      FIG. 6  is an exemplary flow chart of a targeted tissue heating method in accordance with principles of the present disclosure. 
       
    
    
     DESCRIPTION OF EXEMPLARY EMBODIMENTS 
       [0015]    Reference is now made in detail to embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts. The term “distal” refers to a position farther away from a user end of the device. The term “proximal” refers a position closer to the user end of the device. 
         [0016]      FIG. 1  is a schematic view of an exemplary embodiment of the present disclosure, implemented for and in a urinary tract  100  of a human subject  10 . While this disclosure relates to the use of the disclosed system in the urinary tract of a human subject, it is understood that the features of this disclosure could be used in other locations (other organs and tissue) within a human subject. The urinary tract  100  includes, among other structures, a bladder  102  that is in fluid communication with a urethra  104 . Bodily fluid, such as urine, travels down from kidneys  108  to the bladder  102  via ureters  106 . Muscles (not shown) in the walls of the ureters  106  tighten and relax to force the bodily fluid downward and away from the kidneys  108 . The bladder  102  generally accumulates the bodily fluid, which is then discharged from the body through urethra  104 . The bladder  102  includes openings  114 ,  124  for the left ureter and the right ureter, respectively, for receiving bodily fluid from the kidneys  108 . 
         [0017]    A heater or target may be introduced into the bladder  102  for location within the bladder wall  110  at a depth for heating an area in the mucosal layer and the detrusor muscle of the bladder wall  110 . For example, and as will be described in more detail below, the heater may be in the form of a heating element  116  that is embedded into one or more tissue locations  112  in the bladder wall  110 . The heating element  116  may be energized wirelessly by signals  122  sent from a signal generating device  120  located outside the body of the subject  10 . Energizing the heating element  116  by the external device  120  causes the heating element  116  to increase in temperature and sustain heat in portions of the bladder wall  110 . The location of the one or more heater elements  116  within the bladder  102  may be selected according to therapy requirements of the subject  10  suffering from a condition, such as OAB. For example, a plurality of heater elements  116  may be generally evenly distributed within the bladder  102  according to one or more of the tissue locations  112  indicated in  FIG. 1 . 
         [0018]    As shown in  FIGS. 2 and 3 , the heating element  116  may include a distal portion  226  having a helical or coil configuration of a constant and/or varying pitch and extending proximally from a pointed distal tip  228  (e.g., a corkscrew shape). The coil shape may include a lumen size between 1 um and 1 mm. A proximal portion  230  of the heating element  116  may extend proximally from the helical configuration and be generally straight. Other shapes of heating element  116  are possible, for example, distal portion  226  may be provided in any shape that allows for and/or optimizes entry and fixing to the bladder wall  110 , and may include an etched, roughened, or barbed portion to assist in fixation. The proximal portion  230  of the heating element  116  may include any number of grooves or protrusions to assist in transferring the requisite forces from a delivery device  240  ( FIG. 2 ) to the heating device  116 . 
         [0019]    Heating element  116  may be a wire that is fully or partially hollow or solid. The wire may have any cross-section, such as round, flat, square, and/or a combination of such cross-sections. Heating element  116  may be formed of a suitable biocompatible material or materials that are capable of being heated by the signal generating device  120  located outside the body. For example, heating element  116  may be formed from a ferromagnetic material, such as chromium cobalt alloy, stainless steels, iron, nickel and/or cobalt and/or their alloys. Some of such available alloys, characterized by strong ferromagnetism include Co-20Cr-15W-10Ni, Co-20Cr-16Fe-15Ni-7Mo, Co-28Cr-6Mo, Co-35Ni-20Cr-10Mo, or stainless steels: Fe-17Cr-14Ni-2.5Mo, Fe-17Cr-4Ni-4Cu, Fe-18Cr-14Ni-2.5Mo, Fe-19Cr-10Ni, Fe-21Cr-10Ni-3Mn-2.5Mo, Fe-22Cr-13Ni-5Mn-2.5Mo, Fe-23Mn-21Cr-1Mo, Fe-33Pt-18Cr-9Ni-3Mo, Ni-21Cr-9Mo—Nb. Heating element  116  may also be formed from weaker ferromagnetic material such as superparamagnetic iron oxide. Further, as shown in  FIG. 3 , heating element  116  may include a sleeve or coating  380  to assist in preventing corrosion from fluids such as urine within the bladder  102 . The sleeve or coating  380  may cover and extend from a proximal end  382  of the heating element  116  to a location on the distal portion  226  adjacent the depth penetration location  364  of the heating element  116  into the bladder wall  110 . Alternatively, the sleeve or coating  380  may be located only on a straight proximal portion of the proximal portion  230  of the heating element  116 . The sleeve or coating  380  may include one or more polymers such as, polytetrafluoroethylene (PTFE) and Styrene-block-Isobutylene-block-Styrene (SIBS). Proximal portion  230  may also be fully biodegradable over days or weeks; after the heating element  116  is inserted into the bladder wall, the biodegradable portion falls off (excreted with urine) and the remaining ferromagnetic heating element stays behind inside the bladder wall. 
         [0020]    Referring back to  FIG. 2 , the exemplary medical or surgical delivery device  240  is configured to deliver the heating element  116  into the bladder  102 , and to implant the heating element  116  at a desired depth into an internal tissue surface of the bladder wall  110 . The delivery device  240  may include an outer tube  242 , an inner tube  244  located within the outer tube  242 , and an actuator  246  for moving the inner tube  244  proximally and distally with respect to the outer tube  242 . Outer tube  242  may include an open distal end  248  and an open proximal end  250  secured to the actuator  246 . The outer tube  242  and the inner tube  244  may be formed of flexible hypodermic tubing. Embodiments are intended to include outer and inner tubes  242 ,  244  of various applicable dimensions, shapes, and materials. 
         [0021]    The inner tube  244  may include a distal end  252  with a fitting  254  for receiving the proximal end  230  of heating element  116 . The fitting  254  may be a generally cylindrical recess sized to receive a cylindrically shaped proximal end  230  of the heating element  116 . The coupling of the fitting  254  and the proximal end  230  of heating element  116  may be a friction fit that allows for the transfer of rotational motion between the inner tube  244  and the heating element  116 , while still permitting longitudinal decoupling of inner tube  244  and the heating element  116 . Alternatively or additionally, the fitting  254  may include one or more outer or inner surface longitudinal recesses and/or protrusions (not shown) configured to mate with one or more outer or inner surface protrusions and/or recesses (not shown) formed at the proximal end  230  of the heating element  116  so as to assist in the transfer of rotational motion between the inner tube  244  and the heating element  116 . 
         [0022]    Actuator  246  may be connected to the proximal end  250  of the outer tube  242  and include a knob assembly having a knob  256  configured for imparting rotational and longitudinal movement to the heating element  116 . The rotational and longitudinal movement may be achieved by a distal threaded portion  258  of knob  256  that is configured to mate with an inner threaded portion (not shown) of a housing  260  of actuator  246 . As shown in dotted lines in  FIG. 2 , a proximal end  262  of the inner tube  244  may be coupled to a distal end  264  of the threaded portion  258 . The knob  256  may be sized and positioned to partially protrude from a window  264  of the housing  260  so that the knob  256  can be more easily gripped for rotation. Further, knob  256  may include a plurality of gripping protrusions  268  and one or more depth indicator markings  266 . The depth indicator markings  266  may correspond to one or more depth indicator markings  270  on housing  260 . The two sets of depth indicator markings  266 ,  270  can be configured to indicate the extent of longitudinal movement of the knob  256 , and thus the longitudinal movement of inner tube  244  and heating element  116 . 
         [0023]    With reference to  FIGS. 2 and 4 , in an alternative embodiment of the present disclosure, the heater can be a heating substance  400  that is injected into the bladder wall  110  at one or more locations  112  ( FIG. 1 ). The heating substance  400  may be supplied through a hollow needle member  416  that is similar in configuration to the heating element  116  of  FIGS. 1-3 . In contrast to the heating element  116 , hollow needle member  416  may be configured to remain coupled to the inner tube  244  during use. In this embodiment, the inner tube  244  may be fluidly coupled to a lumen  402  extending through the hollow needle member  416 . Further, a lumen of inner tube  244  may be coupled to a supply tube (not shown) that supplies heating substance  400  to the inner tube  244 . For example, knob  256  shown in  FIG. 2  may include a lumen extending therethrough that allows for a fluid coupling of a supply tube to the inner tube  244 . It is understood that other arrangements are contemplated to convey heating substance  400  to the hollow needle member  416 , such as extending the inner tube  244  proximally through a central passage of knob  256  and out a distal end  272  of delivery device  240  to a heating substance supply and injecting mechanism, or merely coupling a needle-type injector through knob  256  and into the lumen of the inner tube  244 . 
         [0024]    In another embodiment, the hollow needle member  416  may be detached after injection of the heating substance  400 . Both the heating substance and the hollow needle member  416  may be heated as disclosed herein. 
         [0025]    Heating substance  400  may be a liquid, gas, or gel that includes ferromagnetic particles suspended in a carrier or medium. The ferromagnetic particles may be in the form of small rods, flakes, coils, wavy wires, and/or beads. Further, it is understood that the ferromagnetic particles may or may not be conveyed in a carrier or medium. The size of the particles  404  may vary from tens of micrometers to hundreds of micrometers, larger than the diameter of blood vessels of the subject, to ensure retention within the targeted tissue of the bladder wall. The particles  404  may also be fabricated of similar ferromagnetic materials as described above for ferromagnetic heating elements  116 . The particles may be composed of two components: a ferromagnetic component and a biodegradable component and the biodegradable component may be loaded with a drug or protein that is released in the bladder wall over time—weeks or months. The biodegradable component (with or without drug) may coat the ferromagnetic particle or it may be attached to the ferromagnetic particle (for example, a ferromagnetic particle and biodegradable particle are attached via covalent, electrostatic, hydrogen, or van der Waals bonds), Possible drugs may be one or more of anticholinergic, imipramine, desmopressin, estrogens, botulinum toxin, intravesical vanilloids, and lidocaine. The ferromagnetic particles  404  may be suspended in suitable medium  406  such as saline and other physiologic liquids such as hydrogels, such as, Polyethylene glycol-electrolyte (PEG), hyaluronic acid, pluronics, carboxymethylcellulose, alginates, chitosan, poly(lactic) acid, poly(lactic-co-glycolic) acid, glucan gel, Ultra Violet (UV) curable gels, and/or complex polysaccharides (e.g. xanthan gum, guar gum). 
         [0026]      FIG. 5  depicts a selective heat application system  500  for providing targeted tissue heating therapy to the bladder  102  of a subject  502  suffering from OAB. The heat application system  500  may include the signal generating device  120  for sending the wireless signals  122  from a location outside the subject&#39;s body  502 . The signal generating device  120  may include magnetic or electromagnetic induction coils made from copper or other suitable materials capable of generating magnetic induction fields of substantial intensity and range, when activated. The size of the induction coil depends on the heat desired to be generated by the heaters ( 116 ,  400 ). The induction coil may be either wound in a two-dimensional fashion in the form of a circle (size of a belt buckle) or it may be wound around the belt of the patient. It is understood that multiple induction coils may be used to generate different amounts of heat in distinct spots. For example, as many induction coils as temperature settings exist may be used such that each induction coil may be tuned to all frequencies of all targets at any time. It is understood that some targets may require treatment at higher temperatures due to, for example, abnormalities leading to increased contractions originating at the target. Alternatively, it is understood that some targets may require treatment at lower temperatures. Accordingly, multiple induction coils may be used to individually provide an appropriate temperature for each target. 
         [0027]    The external signal generating device  120  may be fed from a high frequency alternating current source (not shown) to generate a highly oscillating electromagnetic field, which will interact wirelessly with the magnetic field of the ferromagnetic heaters embedded within the tissue of the subject. The signal generating device  120  may also include other supporting circuitry components for desired operation. Varying the frequency, phase, and/or the amplitude of the power source or the separation between the external signal generating device  120  and the subject  402  influences the heating therapy parameters. 
         [0028]    In another embodiment, external signal generating device  120  may be a Radio Frequency RF transmitter and modulator in wireless communication with RF enabled heaters ( 116 ,  400 ) embedded within bladder wall  102  of subject  402 . The embedded heaters ( 116 ,  400 ) may include RF receivers that share a single frequency for reception, or may be tuned at separate frequency channels. When embedded heaters ( 116 ,  400 ) are tuned for same frequency channel, the RF transmitter in the external device, when excited by suitable power source, communicates with RF enabled embedded heaters ( 116 ,  400 ) on the same frequency channel for heating across the embedded locations  112  in the tissue of the subject  502 . When different embedded heaters ( 116 ,  400 ) have been tuned for different frequency channels, the RF transmitter and the modulator can be configured to jump from one frequency to another to excite the respective RF enabled embedded heaters ( 116 ,  400 ) for simultaneous heat application therapy. 
         [0029]    The external signal generating device  120  may be a hand held device (for example, similar to a hand held ultrasound), or a part of clothing (e.g. a belt buckle), or incorporated in a piece of furniture, such as a bed  504  or chair, to enable wireless heat initiation and control of heat generated in the embedded heaters ( 116 ,  400 ) in the bladder  102  of the subject  502 . Incorporating the signal generating device  120  into a piece of furniture allows the subject  502  to receive therapy in a comfortable position and during extended periods of time, e.g., resting or sleeping. The schedule of heat application therapy may also call for incorporation of the external signal generating device  120  into other devices according to the habits and needs of a subject  502 . The external signal generating device  120  may also be standalone device that can be placed flat and positioned next to the subject body  502 , such as on a belt, or it may be shaped as coil wound around the subject body  502  circumferentially as a belt. The external signal generating device  120  may be located within suitable distances from the subject  502  depending upon the intensity and duration of the heat therapy desired by the subject  502 . The heaters ( 116 ,  400 ) may contain conventional temperature sensors such as a resistance temperature detector (RTD sensor), not shown, configured to wirelessly supply the external signal generating device  120  with temperature measurements indicative of the actual temperature supplied by the heaters ( 116 ,  400 ). The temperature measurements can be used by the signal generating device  120  to maintain a desired temperature or to merely monitor the temperature within the subject. 
         [0030]      FIG. 6  shows a flow chart  600  of an exemplary method for selective heating of target tissue of a subject using wireless communication. The first step  602  may include implanting one or more heaters or targets in the bladder wall of a subject. As discussed above, in the embodiment shown in  FIG. 3  a heater may be in the form of a heating element  116  that is implanted in the subject. In this embodiment, the pointed distal tip  228  of heating element  116  is inserted through a mucosal layer  384  on the surface of a bladder wall  110  and propagates further through in to sub-mucosal layer towards the detrusor muscle  386  of the bladder  102  up to a pre-defined depth within the detrusor muscle  386  of a subject bladder  102 , using delivery device  240 . The rotational movement of the knob  256  of delivery device  240  translates into a longitudinal movement of the helical shaped heating element  116  into the bladder wall  110 . The depth indicator markings  266 ,  270  on delivery device  240  can assist the user of the device in determining the amount of longitudinal movement of the heating element  116 , and thus a depth of penetration into the bladder wall  110 . 
         [0031]    Also as discussed above, in the embodiment shown in  FIG. 4  a heater may be in the form of a heating substance  400  that is injected into the bladder wall  110 . The hollow needle member  416  may be inserted through the mucosal layer  406  and further through sub-mucosal layer of the bladder wall  110 , up to a desired pre-defined depth between the sub-mucosal layer and detrusor muscle  408  using the rotational movement of the knob  256  of delivery device  240  ( FIG. 2 ) that translates into a longitudinal movement of the hollow needle member  416  into the bladder wall  110 . After reaching the desired depth, the heating substance  400  may be injected through the inner tube  244  and lumen  402  of hollow needle member  416  into the bladder tissue between the sub-mucosal layer and the detrusor muscle  408 . 
         [0032]    The heaters ( 116 ,  400 ) may be provided at multiple locations within the bladder wall  110 . For example, the heaters ( 116 ,  400 ) be provided at multiple tissue locations, for example, 10 to 40 sites  112  ( FIG. 1 ) in the bladder wall  110 . 
         [0033]    In step  604  of  FIG. 6 , heat is selectively applied to the one or more heaters ( 116 ,  400 ) by the signal generating device  120  in a wireless manner from outside the subject  502 . The signal generating device  120  may be located in any appropriate location that would generate signals that would effectuate triggering of the heaters ( 116 ,  400 ). In one embodiment, all of the heaters ( 116 ,  400 ) are actuated simultaneously and generate heat in the range of approximately 41 to 43 degrees Celsius. Alternatively, the heaters ( 116 ,  400 ) could be configured to generate heat at different frequencies and produce varied temperatures. The signal generating device  120  may be configured to generate signals at different frequencies and at different times to selectively actuate different heaters ( 116 ,  400 ) at different times and at different locations within the bladder wall  110 . Heat application therapy may be scheduled based on the condition of the subject suffering from, for example, OAB. For example, the heat may be applied according to a preset schedule, or configured to turn on when the bladder  102  has filled to a volume at which contractions usually begin for the subject  502 , and the heat discontinued when the bladder has been voided. Further, heat may be applied to different regions of the bladder  102  of a subject at different times of the day. As discussed above, in one embodiment, the signals may be generated over an extended period of time, such as while the subject is sleeping. 
         [0034]    In step  606 , the heaters ( 116 ,  400 ) may wirelessly supply the external signal generating device  120  with temperature information indicative of the actual temperature supplied by the heaters ( 116 ,  400 ). The temperature measurements can be used by the signal generating device  120  to maintain a desired temperature or to merely monitor the temperature within the subject. 
         [0035]    In some embodiments, one or more targets may be heated to a temperature between about 37 20  C. to about 70° C. As used herein, the terms “about,” “substantially,” and “approximately,” may indicate a range of values within +/−5% of a stated value. 
         [0036]    Embodiments of the present disclosure may be used in various medical, surgical, or non-medical procedures, including any medical procedure where appropriate application of heat or other forms of energy may be desired for target body tissue. The targeted tissue heating for selective and regulated heat application therapy helps to reduce or even treat congenital conditions, such as Overactive Bladder by reducing the number of contractions of the detrusor muscle caused due to local pathological abnormalities. The localized abnormalities such as patchy denervation or increase number of connective tissue between muscles can be reversed or at least stopped from deteriorating further by application of heat at selective tissue intersections to ablate excess tissue formation, and it can also serve to ablate nerve endings to reduce the pathways of communication between the urothelium and the detrusor and nerves. In addition, the method and system detailed out in the different embodiments, in accordance with principles of the disclosure may be implemented to relax various muscles of the subject body to provide relief form tissue tear or rupture. The selective heat application may also address excessive build up of fat for subjects suffering from lifestyles induced ailments, such as, diabetes. The selective heat application may also serve to control peristalsis in the stomach, small and large intestine to slow down or accelerate the contraction and relaxation of muscles to affect the digestive process and feeling of satiety as a possible solution for obese patients. 
         [0037]    As discussed above, the targeted tissue heating is achieved, for example, by the heater material, surface area of the heater, the type and characteristics of the energy conveyed by the heater, and the and the constituents of the tissue surrounding the heater. 
         [0038]    In addition, aspects of the aforementioned embodiments may be combined with any other aspects of any other embodiments, without departing from the scope of the disclosure. 
         [0039]    Other embodiments of the present disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the embodiments disclosed herein. For example, heating element  116  may be configured with a fixed or adjustable stop or marker to help identify the appropriate depth of penetration into the bladder wall  110 . Further, consistent with the disclosure above, the disclosed system is not limited to use in the bladder wall  110 , but can be used in any other tissue or organ in a subject. For example, the heaters could be used in the stomach or duodenum to reduce contractility and to relax these or other muscles in the body. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the disclosure being indicated by the following claims.