Patent Publication Number: US-2010130880-A1

Title: Apparatus and methods for monitoring blood flow in the prostrate gland

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority from U.S. patent application No. 61/028,870 filed 14 Feb. 2008 and U.S. patent application No. 60/912,125 filed 16 Apr. 2007. For purposes of the United States of America, this application claims the benefit under 35 U.S.C. §119 of U.S. patent application No. 61/028,870 filed 14 Feb. 2008 and U.S. patent application No. 60/912,125 filed 16 Apr. 2007, both of which are hereby incorporated by reference herein. 
    
    
     TECHNICAL FIELD 
     This invention relates to monitoring blood flow in the prostate gland. Embodiments of the invention provide methods and systems for treating tumors or other tissues within the prostate gland. 
     BACKGROUND 
     Prostate cancer, benign prostatic hyperplasia and other conditions can cause the prostate to become enlarged. These conditions can result in urinary blockage and other adverse effects on health. These conditions are sometimes treated by selectively heating tissues of the prostate gland. Some systems for heating the prostate gland and tissues use a temperature sensor inserted in the subject&#39;s rectum to measure the amount of heat being delivered to the prostate gland. Since the rectum passes close to the prostate gland, the temperature measured in the rectum can be useful in controlling the application of heat to raise the temperature of the prostate gland. 
     There is a need for improved methods and apparatus for heating the prostate gland which provide better control over the temperatures achieved in the prostate gland. 
     Near Infrared Spectroscopy (“NIRS”) is a technique which involves emitting near infrared (“NIR”) light and receiving the NIR light after it has passed through a tissue or other medium of interest. NIRS can be applied to study and monitor biochemical compounds in the body. Emitted NIR light penetrates skin and other tissues and some of it is absorbed by biochemical compounds which have an absorption spectrum in the NIR region. NIR light which is not absorbed is scattered. Each biochemical compound has a different absorption spectrum. It is possible to estimate the concentration of biochemical compounds in the tissues by measuring characteristics of NIR light that has been detected after it has passed through the tissues. The use of NIRS to measure changes in concentrations of various compounds in living tissues by monitoring appropriate wavelengths is understood by those of skill in the art. 
     SUMMARY 
     This invention provides a range of methods and apparatus that can be used together in various combinations, can be used individually or can be used in combination with other methods and apparatus. 
     Various non-limiting example aspects of the invention and features of example embodiments of the invention are described below. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying drawings illustrate non-limiting embodiments of the invention. 
         FIG. 1  is a cross section through a subject in which apparatus according to the invention is deployed. 
         FIG. 2  is a cross section through a portion of a catheter in a example embodiment of the invention. 
         FIG. 3  is a cross section through a catheter in an alternative embodiment of the invention. 
         FIG. 4  is a cross section through a catheter according to a further alternative embodiment of the invention. 
         FIG. 5  is a cross section through a subject in which apparatus according to another embodiment of the invention is deployed. 
         FIG. 6  is an enlarged schematic view of a rectal probe of the apparatus of  FIG. 5  and associated control systems. 
         FIG. 7  is a schematic plot illustrating gross features of the variation with time of blood flow in a portion of the rectal wall adjacent to a subject&#39;s prostate during heat treatment of the prostate. 
     
    
    
     DETAILED DESCRIPTION 
     Throughout the following description specific details are set forth in order to provide a more thorough understanding to persons skilled in the art. However, well known elements may not have been shown or described in detail to avoid unnecessarily obscuring the disclosure. Accordingly, the description and drawings are to be regarded in an illustrative, rather than a restrictive, sense. 
       FIG. 1  is a partially schematic view of apparatus according to one embodiment of the invention deployed in a subject S. Subject S has a bladder B. The subject&#39;s urethra U extends out of bladder B. Urethra U passes through the prostate gland P. If prostate gland P becomes enlarged or swollen then blockage of urethra U can occur. This can result in significant complications and discomfort. 
     Apparatus  10  comprises a heater  12  that directs energy  14  toward the subject&#39;s prostate gland P. Heater  12  may heat the tissues of the prostate using any suitable modality. For example, heater  12  may comprise one or more of:
         a microwave heater that emits microwave energy that is absorbed in the prostate;   an emitter of light (either visible or invisible light that is absorbed in the prostate and converted to heat);   a radio frequency emitter that emits radio frequency radiation that is absorbed in the prostate;   a source of ultrasound energy that is absorbed in the prostate;   or the like.       

     The output of heater  12  is controlled by a heater controller  16 . Heater controller  16  takes as an input a tissue temperature signal  17  from a tissue temperature sensor  18 . In the illustrated embodiment, tissue temperature sensor  18  comprises a probe  20  that is inserted into the rectum R of the subject. Probe  20  senses the temperature at a point  20 A which is adjacent to the subject&#39;s prostate when probe  20  is inserted into the subject&#39;s rectum R. Temperature sensor  18  and its associated probe  20  are desirable but optional. 
     Heater controller  16  may provide closed-loop control of energy  14  based on feedback from temperature sensor  18  and/or other sensors to achieve a desired temperature within the tissues of prostate P. 
     Apparatus  10  also includes a near infrared spectrometer system (NIRS system)  22  that monitors blood flow in the subject&#39;s prostate. Near infrared spectrometry is a known technique that can be used to monitor for changes in the concentrations of various bio-compounds in living tissues. For example, NIRS can be used to monitor the concentrations of one or more of:
         oxygenated hemoglobin (HbO 2 );   non-oxygenated hemoglobin (Hb); and   total hemoglobin (HbTot);
 
in the prostate or in tissues surrounding the prostate. These concentrations vary with the blood volume which, in turn, varies with blood flow. Levels of cytochrome and/or myoglobin may also be monitored to provide additional information regarding the condition of the prostate.
       

     NIRS involves directing near infrared light from a light source into tissues of interest and detecting the infrared light after it has passed through the tissues of interest. In the illustrated embodiment, a NIRS light source  25  and light detector  26  are provided on a catheter  30  that can be inserted through the subject&#39;s urethra U. An anchoring structure is provided to retain catheter  30  in the subject&#39;s urethra. In the illustrated embodiment, the anchoring structure comprises a balloon  32  on the distal end of catheter  30 . Balloon  32  can be inflated after the distal end of catheter  30  has passed into the subject&#39;s bladder B. Balloon  32  may, for example, be inflated by pumping a fluid into balloon  32  through catheter  30 . Balloon  32  retains catheter  30  in the subject&#39;s urethra. 
     Catheters for insertion into the urethra are known. The details of construction and operation of catheter  30  are not described herein since such details can readily be developed by those skilled in the art, for example by reference to commercially-available catheters. 
     Light source  25  and light detector  26  are spaced apart from balloon  32  by a distance which is suitable to locate source  25  and light detector  26  in the portion of the subject&#39;s urethra U that passes through the subject&#39;s prostate. Light emitted by light source  25  is back-scattered by tissues in the subject&#39;s prostate P and picked up at light detector  26 . An amount of one or more bio compounds related to blood flow for example, oxygenated hemoglobin (HbO 2 ); non-oxygenated hemoglobin (Hb); and/or total hemoglobin (HbTot) may be determined by processing the signal from light detector  26 . The result is that NIRS spectrometer  22  generates a signal  23  indicative of blood flow in the subject&#39;s prostate. 
     Blood flow in the subject&#39;s prostate is important because flowing blood can carry away heat from the subject&#39;s prostate. Heater controller  16  may be programmed to increase the output of heater  12  as blood flow increases (e.g. in response to a measure of blood flow determined by NIRS system  22 ), so as to suitably increase the amount of heat deposited in tissues of the subject&#39;s prostate P to compensate at least partially for heat that is carried away by flowing blood, and thereby raise those tissues to a desired temperature. 
     In some embodiments, heater  12  delivers energy  14  to the subject&#39;s prostate P by way of catheter  30 . For example, energy  14  could be microwave energy that is delivered from a microwave antenna  34  supported in or on catheter  30 . In other embodiments, energy  14  is delivered from outside of the subject. Any suitable mechanism for heating the tissues of the prostate may be used. 
     There are a wide range of ways in which each of NIRS light source  25  and light detector  26  may be provided in a catheter  30 . These can be applied in any combination. Some such combinations are disclosed in the illustrated embodiments. 
       FIG. 2  shows a cross section through one possible configuration of catheter  30 . In the illustrated embodiment, light source  25  comprises a diffuser  40  on the end of an optical fibre  42  that carries optical radiation from a light source  44 . The light propagates along optical fibre  42  from light source  44  to diffuser  40 . At diffuser  40  light  41  is directed out into the tissues surrounding catheter  30 . 
     As an alternative to carrying light along catheter  30  in an optical fibre  42 , NIRS light sources such as suitable light-emitting diodes (LEDs) could be provided in catheter  30  and supplied with electrical power by way of wires or other electrical conductors extending along catheter  30 . 
     Light detectors  26  comprise photo transistors, photo-diodes, or other detectors sensitive to light at the wavelengths emitted by light source  25 . In the illustrated embodiment, there is a plurality of light sensors  26  that sense light incident from different directions and which also include light sensors  26  that are spaced apart from light source  25  by different distances. The depth within the tissues at which the concentration(s) of the monitored bio-compound(s) is measured depends in part on the separation between light source  25  and a light detector  26 . By providing light detectors  26  that are separated from light source  25  by different distances one can determine the blood flow at different depths in the prostate. In  FIG. 2 , the amount of haemoglobin (which varies with blood flow) is detected in regions  45 A, which are closer to catheter  30  and also in regions  45 B, which are farther from catheter  30 . In some embodiments, the NIRS light sources and light detectors include pairs of light sources and light detectors that are spaced apart along catheter  30  by distances in the range of about ½ cm to 2 1/2  cm. 
     A light barricade  46  is disposed between light source  25  and light detectors  26  to prevent light from passing directly from light source  25  to light detectors  26 . In the illustrated embodiment, light barricade  46  has a labyrinth construction to permit the flow of a fluid to inflate balloon  32 . 
       FIG. 3  shows an alternative embodiment of a portion of catheter  30  in which light source  25  comprises a diffuser  48  which releases light propagating in an optical fibre  49 . Light detector  26  comprises a light collector  50  disposed on the end of an optical fibre  52 . In the illustrated embodiment, optical fibre  52  is coaxial with optical fibre  49 . In the illustrated embodiment, the separation between light source  25  and light detector  26  can be varied by sliding optical fibre  52  within optical fibre  49 . A light barrier  54  prevents light from light source  25  from directly reaching light detector  26 . 
       FIG. 4  shows an alternative embodiment in which light source  25  and light detector  26  are both discrete devices located in a lumen  55  of catheter  30 . At least in its portions adjacent to light emitter  25  and light detector  26 , the walls of catheter  30  are transparent to the radiation emitted by light source  25 . Light emitter  25  and light detector  26  may be fixed in catheter  30  or one or both of light emitter  25  and light detector  26  may be movable. 
     As can be appreciated, the construction of the NIRS light source and receiver may be varied in many ways. In some embodiments, one fixed light source and one fixed light receiver may be provided. The light source may emit light that is directed in a particular direction or may emit light so that it radiates in all directions from catheter  30 . In some embodiments, the separation between the light source and detector can be varied. In some embodiments there are a number of pairs of light sources and detectors (for example, one light source and a plurality of different light detectors) in such embodiments the light detectors may be spaced apart by different distances from the light sources so as to sample the concentrations of the bio-compounds being monitored at various depths in the tissue of the prostate gland. 
     In embodiments where there are a plurality of different light receivers  26 , the light receivers  26  may receive light incident on catheter  30  from different directions, thereby making it possible to sense the concentrations of monitored bio-compounds in tissues located on different sides of catheter  30 . 
     In some embodiments, heater controller  16  switches heater  12  on and off (or modulates the output of energy  14 ) in response to the detection of blood flow by NIRS system  22 . Treatment efficacy can be improved by applying heat to tissues of the prostate during periods in which blood flow is below a threshold value and not applying heat during periods wherein the blood flow exceeds the threshold value. 
     In some embodiments, apparatus  10  includes a mechanism  19  (see  FIG. 1 ) for controlling blood flow to the prostate. The mechanism may, for example, comprise a mechanism that clamps off or restricts blood flow in the arteries that supply the prostate. In such embodiments, the mechanism may operate periodically to reduce blood flow in the prostate. The heater controller may cause the heater to operate during such periods of reduced blood flow. 
     In some embodiments, a NIRS light source and receiver are provided on a rectal probe. In such embodiments, the NIRS light source and receiver on the rectal probe may provide an output indicative of blood flow in a portion of the rectal wall close to a subject&#39;s prostate. Changes in the blood flow in the rectal wall can signal the onset of damage to tissues of the rectal wall. Such damage could be caused, for example, by overly-long and/or overly-intense treatment by a heater  12  as described above. 
     In some embodiments, a controller for a heater receives a rectal-wall-blood-flow signal indicative of blood flow in the rectal wall and causes the heater to be reduced in intensity and/or shut down when the rectal-wall-blood-flow signal satisfies a criterion. The criterion may be selected to cause the heating to be reduced or stopped prior to the rectal wall undergoing significant damage. 
       FIG. 5  shows an example embodiment wherein apparatus  60  is deployed in a subject S.  FIG. 5  uses the same reference characters as  FIG. 1  to identify parts of the subject.  FIG. 5  identifies some parts of apparatus  60  that are also found in apparatus  10  with the same reference characters as used in  FIG. 1 . Apparatus  60  differs from apparatus  10  in that it has a probe  62  which supports a rectal-wall blood-flow sensor  64 . Probe  62  optionally also supports a temperature sensor  66  (which may be like temperature sensor  20 A). Heater controller  16  receives signals from rectal-wall blood-flow sensor  64  and also from temperature sensor  66 , if present. 
     In the illustrated embodiment, a rectal wall blood flow monitor  63  receives signals from rectal-wall blood-flow sensor  64  and outputs a rectal wall blood flow signal. In cases where rectal-wall blood-flow sensor  64  generates a signal indicative of blood flow in the rectal wall that can be used directly by heater controller  16  the rectal wall blood flow monitor may not be present or may provide signal conditioning. 
     Rectal-wall blood-flow sensor  64  may comprise any of a variety of blood-flow sensors. For example, Rectal-wall blood-flow sensor  64  may comprise:
         a NIRS sensor;   an ultrasound-based blood-flow detector;   a skin impedance detector; or,   the like.       

       FIG. 6  shows a schematic view of a probe  62  wherein rectal-wall blood-flow sensor  64  comprises a NIRS sensor that includes a NIRS light source  67 A spaced apart from a NIRS light detector  67 B. Sensor  64  is on an aspect of probe  62  that can be placed against the portion of the subject&#39;s rectal wall RW that is adjacent to the prostate P. 
     A NIRS system  68  supplies driving signals to NIRS light source  67 A and receives signals from NIRS light detector  67 B. NIRS system  68  processes signals received from NIRS light source  67 A to derive an output signal indicative of blood flow in the rectal wall. The output signal is supplied to heater controller  16 . 
     In some embodiments, the NIRS system  68  generates outputs which represent concentrations in the rectal wall of one or more of:
         oxygenated hemoglobin;   non-oxygenated hemoglobin;   total hemoglobin;   myoglobin.
 
In some embodiments, rectal wall blood flow monitor generates the rectal-wall blood-flow signal based on one or more of these concentrations.
       

       FIG. 7  shows schematically a curve  70  illustrating a variation with time of a rectal-wall-blood-flow signal indicative of blood flow in the portion of a subject&#39;s rectal wall near the subject&#39;s prostate as might be observed while the subject is receiving a treatment which involves heating the subject&#39;s prostate. 
     A heat treatment is initiated at time  72 . As the heat begins to act on the subject&#39;s prostate and to heat surrounding tissues, blood flow in the subject&#39;s rectal wall initially increases. As the rectal wall begins to suffer damage, the blood flow peaks at  73 . When the rectal wall has become seriously damaged, the blood flow in the damaged portion of the rectal wall declines precipitously. Curve  70  is schematic only and is not based on any specific clinical data. 
     Controller  16  may reduce the output of, or shut off, heater  12  by determining that the rectal-wall-blood-flow signal matches a criterion. The criterion may include, for example:
         determining that the rectal-wall-blood-flow signal has peaked;   determining that the rectal-wall-blood-flow signal is decreasing with time at a rate exceeding a threshold;   determining that the rectal-wall-blood-flow signal is less than or equals a threshold value;   a combination thereof; or   the like.
 
Where the rectal-wall-blood-flow signal is compared to a threshold, the threshold may be based on one or more of:
   a value of the rectal-wall-blood-flow signal prior to or at the outset of treatment (e.g. a value of the rectal-wall-blood-flow signal at a time at or near to time  72 );   a value of the rectal-wall-blood-flow signal at peak  73 ;   a predetermined value;   a value of the rectal-wall-blood-flow signal at a time  74  when a rate of change of the rectal-wall-blood-flow signal with time reaches a threshold amount; and   the like.       

     Apparatus  60  preferably operates to prevent heater  12  from operating in a way that causes lasting damage to the subject&#39;s rectal wall while allowing heater  12  to operate in a way that will provide sufficient heating to the subject&#39;s prostate P to achieve a desired treatment outcome. 
     In alternative embodiments, probe  60  may comprise a plurality of NIRS light sources  67 A and/or a plurality of NIRS light detectors  67 B. In such embodiments, the light sources and light detectors may be arranged in various ways. For example:
         The NIRS light sources and detectors may include pairs of light sources and detectors that are spaced apart from one another by different distances. This permits determining the concentrations of substances such as hemoglobin, at different depths in the adjacent tissue. In general, other factors being equal, NIRS samples more deeply when the NIRS light source and detector are more widely-separated and samples at shallower volumes within adjacent tissues where the NIRS light source and detector are more closely-spaced. In some embodiments, a single NIRS light source (or set of light sources) is associated with a plurality of different NIRS light detectors that are spaced apart from the NIRS light source by different distances. In some embodiments a single NIRS light detector is associated with a plurality of different NIRS light sources that are spaced apart from the NIRS light detector by different distances. For example, the NIRS light source and NIRS light detectors may be arranged at different locations along a straight line or curve. In some embodiments a single NIRS light detector is associated with a plurality of different NIRS light sources that are spaced apart from the NIRS light detector by different distances. In some embodiments, NIRS light sources are paired with NIRS light detectors in a 1:1 relationship.   The NIRS light sources and detectors may include pairs of light sources and detectors that face in different directions from probe  62 . Such embodiments may permit measurement of blood flow in a plurality of different areas of the rectal wall.   The NIRS light sources and detectors may be arranged to provide a plurality of pairs of NIRS light sources and detectors spaced apart by different amounts on each of a plurality of different aspects of probe  62  to permit measurement of blood flow at a plurality of different depths at each of a plurality of different areas of the rectal wall.       

     In embodiments that provide a plurality of pairs of NIRS light sources and detectors, signals from the different pairs of NIRS light sources and detectors may be applied in different ways. In some embodiments, a rectal-wall-blood-flow signal is derived from each of a plurality of NIRS output signals and the rectal-wall-blood-flow signals are each treated separately. In such embodiments, if any one of the rectal-wall-blood-flow signals indicates impending tissue damage to the rectal wall then heater controller  16  may be configured to shut off or reduce the output from heater  12 . In some embodiments, a rectal-wall-blood-flow signal is obtained from a plurality of NIRS output signals. For example: NIRS output signals from differently-spaced pairs of NIRS light sources and receivers may be processed and combined to provide a rectal-wall-blood-flow signal characteristic of blood flow at both shallower and deeper parts of the rectal wall; and/or NIRS output signals from pairs of NIRS light sources and receivers facing in different directions may be combined to provide a rectal-wall-blood-flow signal representative of blood flow over a larger area of the rectal wall than is covered by one pair of NIRS light source and light detector. 
     In some embodiments, heater controller  16  provides a display, or other readout that displays a graph or other indicia indicating one or more blood-flow-signals for the rectal wall and/or prostate. Heater controller  16  may also display indicia indicating when a criterion for shutting off or reducing the output of heater  12  is almost satisfied or has been satisfied. 
     The curve shown in  FIG. 7  is also representative of the gross behavior of blood flow in the prostate as the prostate receives heat treatment. In some embodiments, heater controller  16  monitors one or more prostate blood-flow signals derived from one or more outputs of NIRS system  22  that are indicative of blood flow in the prostate. In such embodiments, heater controller  16  may be configured to continue operation of heater  12  until the one or more prostate blood-flow signals indicate that the heat from heater  12  has succeeded in damaging tissues of the prostate. For example, heater controller  16  could seek to continue operating heater  12  until one or more prostate blood-flow signals from NIRS system  22  indicates that:
         the blood flow in the prostate has peaked and started to decline;   the blood-flow in the prostate is decreasing with time at a rate exceeding a threshold;   the prostate-blood-flow signal is less than or equals a threshold value;   a combination thereof; or   the like.       

     Where the prostate-blood-flow signal is compared to a threshold, the threshold may be based on one or more of:
         a value of the prostate-blood-flow signal prior to or at the outset of treatment;   a value of the prostate-blood-flow signal its peak;   a predetermined value;   a value of the prostate-blood-flow signal at a time when a rate of change of the prostate-blood-flow signal with time reaches a threshold amount; and   the like.       

     For example, unless a rectal-wall-blood-flow signal satisfies a criterion that causes heater controller  16  to discontinue a treatment, heater controller  16  may be configured to continue treatment (by operating heater  12  continuously or intermittently) until one or more of the following is satisfied:
         a predetermined time has elapsed since treatment commenced (the time may be measured, for example, by a timer or timing function built into the controller);   the prostate-blood-flow signal has fallen to a value that is lower than a first threshold;   the prostate-blood-flow signal has fallen to a value that is lower than a fixed or determined percentage of the value that it had at one or more of: a time before, at or just after commencement of treatment; its peak; a time when it had a rate of change more negative than a threshold; or the like;   a predetermined time has passed since a peak of the prostate-blood-flow signal;   etc.       

     In some embodiments, heater controller  16  comprises a data processor that executes software instructions that cause it to control heater  12  as described herein. The software instructions may be stored in a memory accessible to the data processor. Aspects of the invention may be provided in the form of program products. The program products may comprise any medium which carries a set of computer-readable instructions which, when executed by a data processor, cause the data processor to execute a method of the invention. Program products according to the invention may be in any of a wide variety of forms. The program product may comprise, for example, physical media such as magnetic data storage media including floppy diskettes, hard disk drives, optical data storage media including CD ROMs, DVDs, electronic data storage media including ROMs, flash RAM, or the like. The computer-readable instructions on the program product may optionally be compressed or encrypted. 
     In such embodiments, thresholds or other parameters that regulate the operation of heater controller  16  and/or functions that represent criteria for determining whether heater  12  should be shut down or have its output reduced may be stored in a memory accessible to the processor. 
     While a number of exemplary aspects and embodiments have been discussed above, those of skill in the art will recognize certain modifications, permutations, additions and sub-combinations thereof. For example:
         instead of detecting blood flow in the prostate by way of NIRS, blood flow in the prostate may be detected by Doppler ultrasound.   It is not mandatory that catheter  30  be hollow or have a lumen capable of carrying fluids in all embodiments. Catheter  30  may be hollow. The term catheter, as used herein, includes elongated flexible structures that can be inserted into a male person&#39;s urethra but does not require the presence of a lumen or other hollow passage except as otherwise noted or necessarily implied.       

     It is therefore intended that the following claims and any claims hereafter introduced are interpreted to include all such modifications, permutations, additions and sub-combinations as are within their true spirit and scope.