Abstract:
A method of estimating distances in a colon of a subject, including: orally administering to a subject a contrast agent, orally administering an imaging capsule to the subject, emitting radiation from the imaging capsule at a location in the colon, detecting photons that are returned from an interaction of the radiation with an inner wall of the colon and contents of the colon, summating the detected photons with energies corresponding to X-ray fluorescence interactions to form a first count, summating the detected photons with energies corresponding to Compton back-scattering interactions to form a second count, determining the distance from the imaging capsule to the inner wall of the colon and a concentration of the contrast agent at the location of the imaging capsule in the colon using the values of the first count and the second count.

Description:
RELATED APPLICATIONS 
     The present application claims priority from U.S. Provisional application No. 61/344,731 filed on Sep. 23, 2010, the disclosure of which is incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The present disclosure relates generally to imaging the insides of a patient&#39;s colon using an intra-lumen imaging capsule and more specifically to estimating the distance from the capsule to the internal walls of the colon and estimating the size of lesions thereof. 
     BACKGROUND 
     One method of examining the gastrointestinal tract for the existence of polyps and other clinically relevant features that may provide an indication regarding the potential of cancer is performed by swallowing an imaging capsule that will travel through the entire gastrointestinal (GI) tract and view the patient&#39;s situation from the inside. In a typical case the trip can take between 24-48 hours, after which the imaging capsule exits in the patient&#39;s feces. Typically the patient swallows a contrast agent to enhance the imaging ability of the imaging capsule. Then the patient swallows the imaging capsule to examine the gastrointestinal tract while flowing through the contrast agent. The imaging capsule typically includes a radiation source, for example including a radioisotope that emits X-rays or Gamma rays. The radiation is typically collimated to allow it to be controllably directed in a specific direction during the imaging process. In an exemplary case the imaging capsule is designed to measure Compton backscattering and transmits the measurements (e.g. count rate) to an external analysis device, for example a computer or other dedicated instruments. 
     In a typical implementation a radio-opaque contrast agent is used so that a position with a polyp will have less contrast agent and will measure a larger back-scattering count to enhance accuracy of the measurements. Alternatively, other methods may be used to image the gastrointestinal tract. 
     U.S. Pat. No. 7,787,926 to Kimchy, the disclosure of which is incorporated herein by reference, describes details related to the manufacture and use of such an imaging capsule. 
     One challenge in estimating the distance from the imaging capsule to the inner walls of the colon is that the measurements are affected by the radiation blocking ability of the contents surrounding the imaging capsule: generally the contrast agent. The blocking ability of the contrast agent is dependent on the concentration of the contrast agent. Generally the patient can swallow a contrast agent of a specific concentration, however while advancing through the GI tract the water contained in the colon contents is absorbed by the colon leaving a less diluted solution have a higher concentration of contrast agent surrounding the imaging capsule. Additionally in some cases the patient is required to drink more contrast agent at specific times to assure proper functionality of the imaging capsule. Therefore at any specific position the concentration is not known. As a result the distance measurements may not be accurate as desired. 
     There is thus a need for improved methods of measuring the distance from the imaging capsule to the walls of the colon. 
     SUMMARY 
     An aspect of an embodiment of the disclosure relates to a system and method for measuring distances inside a patient&#39;s colon and optionally using the measurements to construct an image of the inside of the colon. The patient swallows a radio opaque contrast agent and then swallows an imaging capsule. The imaging capsule emits radiation at its current location in the colon and then detects photons that are returned from interactions of the radiation with an inner will of the colon and the contents of the colon, for example the contrast agent. 
     Two types of interactions with the radiation produce most of the returned photons: 
     1. X-ray fluorescence; 
     2. Compton back-scattering. 
     The photons of each type of interaction have specific ranges of energy and can be identified by the energy level of the detected photons. The system counts the photons for each energy level and then summates the photons with energy levels corresponding to X-ray fluorescence interactions to form a first count and the photons with energy levels corresponding to Compton back-scattering to form a second count. The first count and second count are then used to determine the distance from the imaging capsule to the inner wall of the colon and to determine the concentration of the contrast agent at the location of the imaging capsule. 
     In an exemplary embodiment of the disclosure, the emitting and detecting are performed on the entire circumference of the inner wall of the colon at the location of the imaging capsule. Optionally, the emitting and detecting are performed repeatedly along the length of the colon as the imaging capsule progresses. 
     in an exemplary embodiment of the disclosure, the information from the detecting is transmitted wirelessly to an external processing device (e.g. a computer) having a program that handles the information. Optionally, the external computer counts the photons according to their energy level and summates them according to the type of interaction that they initiated from. Alternatively, the imaging capsule may summate the photons according to the type of interaction and transmit the results to the computer. 
     In an exemplary embodiment of the disclosure, the determined distances are used to determine the size and location of polyps inside the colon and to construct images of the inside of the colon. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present disclosure will be understood and better appreciated from the following detailed description taken in conjunction with the drawings. Identical structures, elements or parts, which appear in more than one figure, are generally labeled with the same or similar number in all the figures in which they appear, wherein: 
         FIG. 1A  is a schematic cross sectional side view of an imaging capsule deployed in a patient&#39;s colon, according to an exemplary embodiment of the disclosure; 
         FIG. 1B  is a schematic cross sectional view of an imaging capsule deployed in a patient&#39;s colon, according to an exemplary embodiment of the disclosure; 
         FIG. 2  is a schematic illustration of a graph of a count of detected photons, according to an exemplary embodiment of the disclosure; 
         FIG. 3  is a schematic illustration of images of the inside of a colon, according to an exemplary embodiment of the disclosure; 
         FIG. 4  is a schematic illustration of an experiment demonstrating the calculation of distances in the colon, according to an exemplary embodiment of the disclosure; 
         FIG. 5  is a schematic illustration of a graph depicting the experimental results showing the relationship of the photon count, distance from the radiation source and concentration of the contrast agent, according to an exemplary embodiment of the disclosure; 
         FIG. 6A  is a schematic illustration of a graph depicting a surface representing the distance as a function of the count and contrast agent concentration for X-Ray fluorescence, according to an exemplary embodiment of the disclosure; 
         FIG. 6B  is a schematic illustration of a graph depicting a surface representing the distance as a function of the count and contrast agent concentration for Compton back-scattering, according to an exemplary embodiment of the disclosure; 
         FIG. 7  is a schematic illustration of a graph depicting an estimation of distance and concentration for a specific photon count, according to an exemplary embodiment of the disclosure; and 
         FIGS. 8A ,  8 B and  8 C are schematic graphs that demonstrate the relationship between an estimated distance and a real distance as a function of concentration, according to an exemplary embodiment of the disclosure. 
     
    
    
     DETAILED DESCRIPTION 
       FIG. 1A  is a schematic cross sectional side view of an imaging capsule  100  deployed in a patient&#39;s colon  105 , and  FIG. 1B  is a schematic cross sectional view of an imaging capsule  100  deployed in a patient&#39;s colon  105 , according to an exemplary embodiment of the disclosure. In an exemplary embodiment of the disclosure, the patient first drinks a contrast agent  140  that mixes with the colon contents. The contrast agent  140  assists in enabling the imaging capsule  100  to perform measurements and form a 3-dimensional image of colon  105  from the inside. Optionally, the contrast agent  140  includes water mixed with a radio opaque material with a relatively high atomic number such as, for example, Barium (atomic number 56) or Iodine (atomic number 53). After drinking the contrast agent  140  the patient swallows imaging capsule  100 . Imaging capsule  100  travels through the patient&#39;s GI tract and through the colon until it exits in the patient&#39;s feces. 
     In an exemplary embodiment of the disclosure, imaging capsule  100  includes a radiation emitter  120  and a radiation detector  130 . In some aspects, the radiation emitter  120  provides a collimated radiation beam that emits radiation while rotating 360 degrees inside imaging capsule  100  to scan the entire inner circumference of the colon walls  110  as the imaging capsule progresses through the colon. In an exemplary embodiment of the disclosure, radiation detector  130  rotates with radiation emitter  120  to detect the photons that are returned from interactions with the emitted radiation. In some aspects, radiation detector  130  may include detectors surrounding the outer circumference of imaging capsule  100  to detect radiation from all sides of imaging capsule  100 . in some aspects, radiation detector  130  may he a solid state detector, for example a Cadmium Telluride (CdT 1 ) compound serving as a detector. In an exemplary embodiment of the disclosure, imaging capsule  100  emits X-ray radiation and measures photons returned by two physical phenomenon causing interactions with the radiation. In an exemplary embodiment of the disclosure, the two physical phenomenons are Compton back-scattering and X-ray fluorescence. The measured photons related to these phenomenon are used to determine the distance  160  from imaging, capsule  100  to the surrounding walls  110  of the colon or the distance  150  to polyps  115  extending from the inner walls  110  of the colon  105 . 
     In an exemplary embodiment of the disclosure, imaging capsule  100  includes a transmitter  135  (e.g. an RF transmitter) to transmit the measurements to an external processing device  190  for processing. In an exemplary embodiment of the disclosure, processing device  190  is a general purpose computer with an executable program  195  that accepts the measurements from the imaging capsule  100 . Optionally, program  195  determines the distances (e.g.  150  and  160 ) inside colon  105  and constructs a 3 dimensional image of the colon for a medical practitioner to view. Optionally, the processing device  190  also determines the width  170  and height ( 160 - 150 ) of polyps extending from the colon walls  110 . In an exemplary embodiment of the disclosure, imaging capsule  100  travels in the longitudinal direction through the colon. The imaging capsule  100  may be off center sometimes during the journey. In an exemplary embodiment of the disclosure, program  195  compensates for deviations from the center by using the measurements that are performed on the entire circumference inside the colon and adjusting the results if necessary. 
     In some embodiments of the disclosure, imaging capsule  100  may include an internal processing device and transmit 3-dimensional images directly to an external viewing device for the medical practitioner to view. 
     In an exemplary embodiment of the disclosure, the radiation emitter emits X-ray radiation, for example between 10 to 100 KeV (e.g. 59.4 KeV). Optionally, the X-ray photons interact with the contrast agent, the contents of the colon and the tissue of the colon walls  110 . The interactions cause the return of photons to detector  130  based on two physical phenomenons: 
     1. Compton back-scattering (CMT)—The X-ray photons emitted from imaging capsule  100  collide with the electrons of the colon content and the tissue of the colon walls  110  and provide back-scattered photons of specific energies, which are detected by detector  130 . Additionally, the backscattered photons are attenuated by the distance traveled. The larger the distance that the back-scattered photons travel through the contrast agent  140  the less the number of back-scattered photons that will be detected since the contrast agent enhances absorption of the photons. When a polyp  115  exists on the colon wall  110  the distance is shorter, less contrast agent absorbs the photons and more will he detected by detector  130 . 
     2. X-ray Fluorescence (XRF)—The X-ray photons emitted from the imaging capsule interact with the atoms of the contrast agent and the rest of the contents of the colon  105 , The interactions cause ionization, which yields a fluorescent photon flux with specific energy levels from the heavy atoms in the contrast agent such as Iodine or Barium. Additionally, the larger the distance from imaging capsule  100  the more X-ray fluorescence will be detected and the shorter the distance the less X-ray florescence will be detected. 
     The photon energy (KeV) far the photons released by each of the two physical phenomenon is different so the results from each phenomenon can be analyzed independently. FIG,  2  is a schematic illustration of a graph  200  of a count of detected photons, according to an exemplary embodiment of the disclosure. In a. typical case the X-ray fluorescence forms the two highest peaks on the of left side of the graph (lower energies) and the Compton back-scattering forms the highest peak on the right side of the graph (higher energies). The energies of the peaks are generally known since they depend mainly on the energy of the emitted radiation, the compounds in the contrast agent and the geometry between the radiation emitted and the detector&#39;s position relative to the emitter. 
       FIG. 3  is a schematic illustration of images  300  of a colon, according to an exemplary embodiment of the disclosure. Image  310  shows a computer reconstructed cross sectional perspective. view of the inside of colon  105  with a polyp  115  on the bottom surface. Image  310  is reconstructed based on the measurements of imaging capsule  100 . Image  320  shows a longitudinal side view of the inside of the colon  105  with polyp  115  and image  330  shows a cross sectional view of the colon at the position of the polyp  115 . 
     Following are details of an experiment  400  conducted to demonstrate the connection between the distances ( 150 ,  160  and  170 ) and the results measured. from Compton back-scattering and X-ray fluorescence as described above.  FIG. 4  is a schematic illustration of the setup of experiment  400  to demonstrate the calculation of distances in the colon  105 , according to an exemplary embodiment of the disclosure. In an exemplary embodiment of the disclosure, a tank  410  of water mixed with a contrast agent  430  is used to demonstrate colon  105 . A slab  420  of plastic with the same density as water is used to demonstrate the colon tissue and the tissues beyond. A collimated radiation source  440  emitting X-ray radiation at 59.4 Key (e.g. using an Am 241  radiation source) is used to provide X-ray radiation. A solid state (CdT 1 ) radiation detector  450  counts photons that are released responsive to the X-ray radiation. The measurements are provided to a transmitter  460  that transmits the measurements wirelessly to processing device  190 , such as, for example, a computer that executes program  195 . 
     In an exemplary embodiment of the disclosure, slab  420  was positioned at various distances (e.g. 0-30 mm) relative to the radiation source  440  to see the effect on the measurements. Additionally, the measurements were repeated for various concentrations of contrast agent  430 , for example 1% -8%. The graph in  FIG. 2  shows a typical spectrum with two areas: 
     1. Area  210  representing the results from X-ray florescence with 2 peaks, for example one large and one smaller between 30 KeV and 35 KeV, and 
     2. Area  220  representing the results from Compton back-scattering with a peak, for example between 40-45 KeV. 
     The results of area  210  and area  220  for various distances and contrast agent concentrations were integrated and provided in graphical form.  FIG. 5  is a schematic illustration of a graph  500  depicting the experimental results showing the relationship of the photon count, distance from the radiation source and concentration of the contrast agent, according to an exemplary embodiment of the disclosure. The lower lines correspond to X-ray fluorescence and the upper lines correspond to Compton back-scattering. Each line represents a different concentration percentage for various distances. As shown in graph  500  the more concentrated the contrast agent the greater the count the for X-ray fluorescence and the lower the count for Compton back-scattering. Likewise the greater the distance from the radiation source the greater the count for X-ray fluorescence. and the lower the count for Compton back-scattering. 
     In an exemplary embodiment of the disclosure, program  195  is required m determine the distance L as a function of the counts (I) of the X-ray florescence and Compton back-scattering (i.e. L=L(I CMT , I XRF )). 
       FIG. 6A  is a schematic. illustration of a graph  600  depicting a surface representing the distance (L) as a function of the count (I) and contrast agent concentration (Ro) for X-Ray fluorescence, and  FIG. 6B  is a schematic illustration of a graph  650  depicting a surface representing the distance (L) as a function of the count (I) and contrast agent concentration Ro) for Compton back-scattering, according to an exemplary embodiment of the disclosure. 
     In an exemplary embodiment of the disclosure, for specific count values (I CMT , I XRF ) at a specific moment (when the imaging capsule is at a specific position) a set of 2 functions can be obtained from the surfaces in graphs  600  and  650  providing an estimated distance (L EST ) as a function o the concentration of contrast agent  430  (a line on the surface representing a specific concentration):
 
L EST   =L   CMT (Ro, I CMT =constant); and
 
L EST   =L   XRF (Ro, I XRF =constant).
 
     Optionally, program  195  finds the intersection point of the 2 curves yielding the estimated distance L EST  and the concentration (Ro).  FIG. 7  is a schematic illustration of a graph  700  depicting an estimation of the distance L EST  and concentration (Ro) for a specific photon count, according to an exemplary embodiment of the disclosure. 
     In an exemplary embodiment of the disclosure, during live application of imaging capsule  100  through a patient&#39;s colon  105 , various disturbances may hinder the calculations described above and disturb the smoothness of the results, for example the concentration of the contrast agent varies throughout the colon  105 . Additionally, the concentration is lower at the beginning and increases toward the exit from the colon due to absorption of water from the colon leaving the molecules of the contrast agent at a higher concentration. In order to overcome disturbances the following method and assumptions are used: 
     1. The contrast agent concentration (Ro) is assumed to change gently along the colon tract. 
     2. The results of the concentration will be calculated based on the estimation calculations used above. 
     3. The concentration for a sequence of positions will be filtered by regression to provide a smooth function. 
     4. The smoothed concentration function will be used to estimate the distance  160  either using the Compton back-scattering curve or the X-ray fluorescence curve (as shown in  FIG.7 ):
 
 L   EST   =L   CMT ( Ro   smooth   , I   CMT =constant) or  L   EST   =L   XRF ( Ro   smooth   , I   XRF =constant).
 
     In an exemplary embodiment of the disclosure, the performance of the estimation calculation is evaluated by comparing the estimated distance (L EST ) to the real (L REAL ) distance in the experiment described above.  FIGS. 8A ,  8 B and  8 C are schematic graphs that demonstrate the relationship between the estimated distance and the real distance as a function of the concentration (Ro). The figures show two dotted outer lines showing the boundaries of the results based on the measurements and two inner lines one showing the standard deviation of the measured results and one showing the mean of the measured results.  FIG. 8A  shows the relationship for Ro=8%,  FIG. 8B  shows the relationship for Ro=6% and  FIG. 8C  shows the relationship for Ro=4%. The results of the graph show that good results can be obtained for distances up to 20 mm with a concentration of 8% and larger distances for lower concentration. Typically imaging capsule  100  will travel along the longitudinal direction, which has a typical diameter of 30-40 mm and a maximum of up to about 50 mm. However it should be noted that during movement, the colon typically contracts to less than 50% of its normal diameter leaving a short distance between the colon wall  110  and imaging capsule  100  in the order of 5-15 mm at the most. 
     In an exemplary embodiment of the disclosure, after calculating the distance from imaging capsule  100  to the colon walls  110  other measurements may be calculated based on the results. In an exemplary embodiment of the disclosure, the width (D)  170  ( FIG. 1B ) of a polyp  115  can be estimated by calculating an angle (A)  180  enclosing the polyp  115 , for example the angle between two scanning positions during rotation of the radiation source where the length is larger than the length over width D because of the polyp  115  or that the length is substantially the same as the rest of the circumference except over width D. Additionally, geometric calculations can be used to determine the width of polyp  115 , for example by calculating D=2*L*Tan(A/ 2 ). 
     It should be appreciated that the above described methods and apparatus may be varied in many ways, including omitting or adding steps, changing the order of steps and the type of devices used. It should be appreciated that different features may be combined in different ways. In particular, not all the features shown above in a particular embodiment are necessary in every embodiment of the disclosure. Further combinations of the above features are also considered to be within the scope of some embodiments of the disclosure. 
     It will be appreciated by persons skilled in the art that the present disclosure is not limited to what has been particularly shown and described hereinabove.