Abstract:
A capsule for determining the blood content of living tissue in vivo in a patient to detect tumors. The capsule includes a light source and a light detector for directing light onto the tissue and for receiving interacted light therefrom. By analyzing the interacted light, a determination can be made of the blood content of that tissue. There are various ways of positioning the capsule so that it contacts the tissue in the desired orientation of the light source and light detector. There is also a system for determining the actual contact between the capsule and the tissue. A calibration system is also used that allows a self calibration that can be carried out easily and accurately just prior to the use of the capsule.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is related to U.S. patent application Ser. No. 11/937,153 filed concurrently herewith, entitled “Method and Solution for Correlating Image and Tissue Characteristic Data” and U.S. patent application Ser. No. 11/937,133, filed concurrently herewith, entitled “Blood Content Detecting Capsule,” now U.S. Pat. No. 8,162,828 issued Apr. 24, 2012, both of which are herein incorporated by reference. 
     FIELD OF THE INVENTION 
     The invention relates to the use of capsule type endoscopes in patients. More specifically, the invention relates to detecting, positioning, and calibrating capsule type endoscopes for use in a living patient with the goal of utilizing blood content detection to locate and determine abnormalities in living tissue. 
     BACKGROUND OF THE INVENTION 
     Endoscopes have long been used by physicians to enter into the internal area of a patient in order to carry out function at that location. Traditionally, the endoscope comprises an optical system and an illumination system that enable the physician to locate the distal end of the endoscope in the desired area to enable the physician to view that area at a location external of the patient. 
     More recently, there has been developed capsule endoscopes which are capsules containing image capture devices, such as digital cameras, that are swallowed by the patient and travel to a location of interest within the patient, such as the intestinal track, to study the colon in a search for lesions. Once at that location, the capsule endoscope gathers captured images to aid the physician to carry out some diagnosis of the patient. 
     Moreover, scientists have discovered a detectible increase in the blood content of superficial mucous membrane proximate cancerous and precancerous lesions in the colon as described, for example, in R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman,  Increased Microvascular Blood Content is an Early Event in Colon Carcinogenesis , Gut Vol. 54, 654-660 (2005), which is incorporated by reference herein. This phenomenon is referred to as an early increase in blood supply (EIBS). 
     BRIEF SUMMARY OF THE INVENTION 
     The invention relates to swallowable capsules having the capability to measure blood content of tissue comprising, for example, the digestive track. Exemplary configurations of such devices are described in related corresponding patent applications entitled “Method and Solution for Correlating Image and Tissue Characteristic Data” and “Blood Content Detecting Capsule” co-filed herewith and incorporated by reference herein. Such devices enable doctors and clinicians to detect EIBS for screening of lesions or tumors or when combined with image capture devices within the capsules facilitate the location of cancerous and pre-cancerous lesions or tumors. 
     Exemplary configurations for such capsule include, for example, a light source that emits polarized light onto a region of the superficial mucous membrane and a light detector that receives light interacted with that tissue and the hemoglobin contained therein. The interacted light from the tissue is returned at a different polarization angle than the emitted light. This return angle and magnitude of the detected interacted light can be measured and is indicative of the blood content in that mucus tissue. Thus, the information relative to the blood content can be transmitted by the capsule to a receiving instrument external of the patient so that the physician can monitor the blood content in the tissue and use that information in determining the existence or proximate location of a lesion. A technique for the measurement of Hb through the use of polarized light has been disclosed in Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and V. Backman,  Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer , IEEE J. Sel. Top. Quant. Elec., Vol. 9, 243-256 (2003) and M. P. Siegel, Y. L. Kim, H. K. Roy, R. K. Wali, and V. Backman,  Assessment of blood supply in superficial tissue by polarization - gated elastic light - scattering spectroscopy , Applied Optics, Vol. 45, 335-342 (2006) and the entirety of those articles are incorporated herein by reference. 
     However, one issue confronted by such a capsule is that it is necessary for the capsule to be in direct contact with the tissue, or at least in extremely close proximity thereto for the light source and light detector to accurately detect blood content. As such, because the capsule itself is not readily maneuverable within the patient, there must be system that enables the capsule to be positioned in the proper orientation with respect to the tissue. Another issue with the use of such a capsule is that it is further important that there be some system that verifies the existence of the contact so that the capsule can actually obtain valid information as to the blood content in that tissue. Also, it is important that there be some calibration system for the blood content detection system of the capsule that is extremely reliable and that can be used on site prior to use with a patient. 
     The present invention provides methods and capsule devices that overcome these issues. In accordance with the present invention, a capsule is provided that is small enough to be swallowed by a patient and it has a blood content detector contained therein. The blood content detector includes a light source and a light detector oriented such that polarized white light from the light source travels through a measurement widow formed in the capsule to impinge upon living tissue of the patient where interacted light from the tissue and hemoglobin contained therein is detected by the light detector. The angle of the reflected light is analyzed as indicative of blood content in that tissue and generates signals representative of that blood content that are transmitted to a data processing means, such as a computer, where the information as to the blood content is processed and made available to a user. 
     As such, the present invention includes various means to orient the capsule so that it is in actual contact with the tissue being analyzed and the light impinges upon the tissue. To that end, one embodiment uses the shape of the capsule to achieve the desired orientation. Another embodiment provides weights strategically located within the capsule to bring about the desired orientation and yet another embodiment has the blood content detector mounted within a inner module that is movable within an outer capsule. In one exemplary embodiment, mirrors are provided to direct the light from the illuminating means to the light receiving means in order to further miniaturize the capsule. 
     The present invention also includes a proximity detector that detects the proximity of the capsule detector to the living tissue and, in particular, to verify when there is an actual contact between the capsule and that tissue. The proximity detector can be of various types and may include a distance detection system that determine the distance between the capsule and the living tissue so that a signal can be provided as that actual contact is imminent so that a blood content measurement can be taken at the time of contact. 
     Finally, there is a calibration system that can be used to calibrate the capsule easily and accurately just prior to the time of use. 
     These and other features and advantages of the present invention will become more readily apparent during the following detailed description taken in conjunction with the drawings herein. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic view of an exemplary in vivo sensing system in accordance with the present invention; 
         FIG. 2  is a cross sectional diagram showing an exemplary capsule constructed in accordance with the present invention; 
         FIG. 2  is a schematic view of an exemplary embodiment of the capsule; 
         FIG. 3  is block diagram illustrating the functions carried out within an exemplary processing apparatus of the present invention; 
         FIG. 4  is a cross sectional schematic showing an exemplary shape of a capsule in accordance with the present invention; 
         FIG. 5  is cross sectional schematic showing a further exemplary embodiment of the invention; 
         FIG. 6  is a cross sectional diagram showing another exemplary embodiment of the present invention; 
         FIGS. 7A-7B  are cross sectional diagrams illustrating the exemplary use of weights to position a blood content detector of the present invention; 
         FIG. 8  is a cross sectional diagram illustrating an alternate orientation system of the present invention relative to that shown in  FIGS. 7A-7B ; 
         FIGS. 9A-9D  are cross sectional diagrams illustrating a further orientation system of the present invention; 
         FIG. 10  is a schematic view of an alternate embodiment of the present invention using mirrors to guide the light traveling to and from the tissue of the patient; 
         FIG. 11  is a schematic view of a further exemplary embodiment utilizing mirrors in the light path; 
         FIG. 12  is a cross sectional diagram of the present capsule having various proximity detecting systems; 
         FIG. 13  is a graph plotting time vs. distance between a capsule and the living tissue of a patient; 
         FIG. 14  is a cross sectional diagram illustrating a calibration system usable with the present invention; and 
         FIG. 15  is a cross sectional diagram illustrating an alternate calibration system usable with the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring first to  FIG. 1 , there is shown a schematic view of an in vivo sensing system illustrating the use of the present invention. In  FIG. 1 , therefore, there can be seen a capsule  10  that is moving slowly in the colon  12  of a patient  14  and an external processing unit  16  that receives data sent from the capsule  10 , analyzes that data and displays the result. The stream of data and information can be, for example, communicated wirelessly along the path  18  to the external processing unit  16 . 
     In an exemplary configuration of the capsule  10 , two pieces of spectrum information of body living tissue are acquired to obtain information about the blood content in the superficial portion of the mucous membrane or other living tissue. This embodiment uses a polarization spectrum of a first orientation having the same polarization direction as incident light from a capsule light source, referred to as a horizontal polarization and a corresponding orthogonal polarization spectrum which has the polarization direction perpendicular to incident light from the capsule light source. As stated, a technique for determining the hemoglobin content of tissue through the use of polarized light has been disclosed in Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and V. Backman,  Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer , IEEE J. Sel. Top. Quant. Elec., Vol. 9, 243-256 (2003) and M. P. Siegel, Y. L. Kim. H. K. Roy, R. K. Wali, and V. Backman,  Assessment of blood supply in superficial tissue by polarization - gated elastic light - scattering spectroscopy , Applied Optics, Vol. 45, 335-342 (2006) and the entirety of those articles are incorporated herein by reference. 
     In this embodiment, a difference operation between the first or horizontal polarization spectrum and the perpendicular polarization spectrum is performed in the capsule  10  and the result is transmitted to the processing unit  16 . It is alternatively suitable in accordance with the invention for the difference operation to be carried out in the processing unit  16  or other external device whereby data indicative of the horizontal polarization spectrum and the perpendicular spectrum are sent to the processing unit  16  by the capsule  10 . 
     Referring now to  FIG. 2 , there is shown a cross sectional diagram showing the construction of an exemplary capsule  10  of the present invention. As can be seen, the capsule  10  comprises an enclosure  20  with the components of the device encased within the enclosure  20 . The enclosure  20  is designed to be of a size that is relatively easy for a patient to swallow and can generally have a diameter of approximately 10 mm. 
     Contained within the enclosure  20 , there can be seen a blood content detector  22  which includes various components used to determine the blood content of living tissue by means of an optical detector. There is, therefore a light detector  28  and a light source  24  including, for example a white LED  26 . The path of the light travels in the direction of the arrows A, where the wide angle light is absorbed by light absorbing member  30  so that only a narrow angle of light (close to parallel light) can pass through an opening  32  after passing through a linear polarizing element  34  where the light is polarized. By reducing the size of the opening  32 , the illuminated region of tissue can likewise be reduced. A suitable size of an illumination region can be, for example, in the range of approximately 0.1 mm 2  and 100 mm 2 . 
     The polarized light thereafter passes through a lens  36  and opening  32  and the linear polarizing element  34  are disposed along the location of the focal length of the lens. As such, the light coming for the light source  24  and is a narrow-angle light that impinges on a small region of tissue. Furthermore, it is possible to alter the direction in which the parallel light travels by using lens to direct through a measurement window  38  to impinge upon living tissue  40  of the patient in vivo. 
     Interacted light from living tissue  40  and the hemoglobin contained therein returns along the direction of the arrows B to the light detector  28  as light with a specific reflection angle. As can be seen, the return interacted light passes again through the optical light path converter  36  where the light thereafter passes through two linear polarizing elements, that is, a first linear polarizing element  42  and a second linear polarizing element  44  that are orthogonal to each other. By that means, the linear polarizing elements  42  and  44  transmit beams of polarized light perpendicular to each other and the polarization direction of the first linear polarizing element  42  of the light receiving means  28  is the same as that of the linear polarizing element  34  of the illuminating means  24 , and the second linear polarizing element  44  passes through the polarization spectrum orthogonal thereto. Beams of light that have been transmitted through each of the linear polarizing elements  42 ,  44  are passed on by a transmissive grating  46  in the directions with the different diffusion angles for each wavelength of light. That light then is sensed by a light sensor  48 . 
     By doing so, each wavelength component of light can reach different locations on a light sensor  48  which enables spectroscopy in two kinds of polarization states; the horizontal polarization spectrum and the perpendicular polarization spectrum. Measured spectrum data is then sent to a data transmitter  50  where it is transmitted to the processing unit  16  of  FIG. 1 . A power supply  52  powers the components of the capsule  10 . 
     Turning now to  FIG. 3 , there is shown a block diagram illustrating the functions carried out within the processing unit  16 . Initially there is a data receiving means  54  that receives the information and data from the capsule  10  ( FIG. 1 ) via an antenna  56 . In the embodiment, although wireless radio transmission is expected, data transmission using alternative techniques such as acoustic or infrared schemes are likewise useable in accordance with the invention. In such case, a data transmitter in the capsule and a data receiver in the processing unit would be provided that conform to another&#39;s technology, accordingly. 
     The data received by the data receiver  54  is provided to a data preprocessor  58 . The data preprocessor  58  executes white correction. Equation (1) shows an example of white correction.
 
Δ Ic (λ)=Δ I (λ)/Δ Iw (λ)=( I   II (λ)− I ⊥(λ))/( Iw   II (λ)+ Iw ⊥(λ))  (1)
 
     In equation (1), λ represents wavelength. ΔI(λ) indicates the measured difference polarization spectrum. ΔIw(λ) is a spectrum measured by using what is known as a standard white plate and is calculated by summing the white horizontal polarization spectrum Iw II (λ) and the white perpendicular polarization spectrum Iw ⊥ (λ) as shown in the denominator of equation (1). In the numerator of equation (1), the difference between the horizontal polarization spectrum I II (λ) and the perpendicular polarization spectrum I⊥(λ) is calculated in data transmitter  50  and a signal indicative of ΔI(λ) is transmitted by data transmitter  50  to the processing unit  16 . 
     The blood content estimator  60  calculates the blood content by using equation (2) below, which is shown in, for example, M. P. Siegel, Y. L. Kim, H. K. Roy, R. K. Wali, and V. Backman,  Assessment of blood supply in superficial tissue by polarization - gated elastic light - scattering spectroscopy , Applied Optics, Vol. 45, 335-342 (2006).
 
Δ I (λ)=Δ I   scattering (λ)exp[−α A   PG (λ)]  equation (2)
 
     As stated, the blood content estimator  60  calculates the blood quantity by using a model equation, such as equation (2), and provides a corresponding blood content value to an indicator such as, for example, display  62 . The corresponding blood characteristic information can then be displayed to the user by display  62 . In addition there is a power supply  64  to power the processing unit  16  and a controller  66  to carry out the various control functions needed to process and display the information. 
     Turning now to  FIG. 4 , there is shown a schematic view of exemplary embodiment of the capsule  10  wherein cross section of enclosure  20  is a substantially elliptical shape. Because enclosure  20  has the substantially elliptical shape, the elongated regions along larger curvature B will more likely be positioned along tissue as it traverses the digestive tract than the region of smaller curvature A. Thus, measurement window  38  is located in the region along the larger curvature B. 
     Returning briefly to  FIG. 2 , it can be seen that the measurement window  38  is disposed in that downward location. The measurement window  38  is disposed in such location in  FIG. 2  and the lens  36 , the light source  24  and the light detector  28  are disposed on the device facing the measurement window  38  in order to direct the illumination light on a desired location of the living tissue  40 . 
     While the capsule  10  in the prior exemplary embodiment is based upon orienting the measurement window by the characteristic shape of the capsule enclosure  20 , a further exemplary embodiment achieves the proper orientation by means of the weight balance of the capsule enclosure  20 . 
     Accordingly, turning to  FIG. 5 , there is shown a capsule  10  where the enclosure  20  itself is circular in cross section and weights  68  are provided proximate the measurement window  38 . The weights  68  are provided at a location away from the center of the capsule  10 . When the center of gravity deviates from the center of the enclosure  20 , the outer surface of the enclosure  20  in the deviated direction is likely to come into contact with the living tissue  40  of the patient as shown in  FIG. 5 . 
     As such, the measurement window  38  in this embodiment is located along the outer surface of the capsule enclosure  20  in the deviated direction, thus locating the measurement window  38  in the desired position contacting the living tissue  40  so as to attain the same effect as the embodiment of  FIG. 4 , the difference being that with this embodiment, the orientation of the capsule  10  is achieved by the addition of weights  68 , whereas with the prior embodiment, the desired orientation was achieved by the shape of the capsule  10  itself. 
     Turning now to  FIG. 6 , there is shown a cross sectional diagram showing the exemplary embodiment of  FIG. 2  using the same identification numbers as were used in  FIG. 2  for corresponding features. As can be seen in  FIG. 6 , however, there has been added the weights  68  that are located at the sides of the measurement window  38  so as to orient the capsule  10  in contact with the living issue  40  in order to properly direct the light toward the living tissue  40  and to receive the return reflected light. 
     The weights  68  can be made of metal such as stainless steel or glass with a relatively high specific gravity. Even when the shape of the capsule  10  is of an elliptical shape as shown in  FIG. 4 , the measurement window  38  may be located in any given position by means of a weight. As can be seen in  FIGS. 7A and 7B , even if the measurement window cannot be disposed or located in the desired position as shown in  FIG. 7A , a measurement can be made as shown in  FIG. 7B . As can be seen, the weight of the weight  68  is not specified and may vary according to the design of the capsule. It is established so that the measurement window faces downwardly when the capsule  10  is disposed on a flat panel set perpendicular to the vertical direction. 
     Turning next to  FIG. 8 , there is shown a cross sectional diagram showing another exemplary embodiment of the present invention. In this embodiment, instead of the use of weights, the desired orientation of capsule  10  is achieved by deviating the center of gravity from the center of the capsule  10 , i.e., that is, by changing the layout within the capsule  10 . In  FIG. 8 , the center of gravity can be made to deviate by partially placing a hollow or lightweight part  46  in the upper position so that the measurement window  38  faces downwardly to contact the living tissue  40 . 
     Turning now to  FIGS. 9A-9D , there is shown a still further exemplary embodiment of the present invention. In this embodiment there is an outer capsule  72  that is comprised of a transparent material to allow the transmission of light therethrough. Within that outer capsule  72 , there is disposed a moveable inner module  74  having mounted therein, the blood content detector  22 . As such, in  FIG. 9A , there is a cross sectional diagram of the inner module  74  and in  FIG. 9B , there is a cross sectional diagram of the outer capsule  72 . In  FIG. 9C , there can be seen the inner module  74  movably mounted within the outer capsule  72 . The movement of the inner module  74  can be accomplished by, for example, a gimbal arrangement, not shown, that can be a conventional mounting mechanism that permits the blood content detector  22  to move therein. 
     In  FIG. 9D , there is shown a cross sectional diagram taken along the line  9 D- 9 D of  FIG. 9C  illustrating the movement of the inner module  74  from its position at location X to its position at location Y. Accordingly, at position X, it can be seen that the measurement window  38  is located to the side and not facing the living tissue  40  where it must be to take a reading of the blood flow in that living tissue  40 . The weights  68  thus operate to bring the inner module  74  to its position at location Y where the free movement of the inner module  74  within the outer capsule  72  repositions the measurement window  38  to the desired position contacting the living tissue  40  for a blood content reading. In this embodiment, the outer capsule  72  can have a substantially circular cross-section ellipsoidal shape as well as other possible shapes. 
     Turning now to  FIG. 10 , there is shown a schematic view of the present invention where the lens ( FIG. 2 ) has been replaced with a mirror arrangement in order to result in further miniaturization of the capsule  10 . As such, with this embodiment, the light emitted by the light source  24  is reflected by two mirrors, a first mirror  76  and a second mirror  78  as that light passes through the window  38  to reach the living tissue  40 . In a similar manner, the interacted light from the living tissue  40  is reflected off of two mirrors, the common, second mirror  78 , and a third mirror  80  prior to reaching the photodetector  82 . As can be seen the optical axis to the mirrors is inclined or at a non-90 degree angle with respect to the measurement window  38  so as to eliminate reflections from surfaces of the measurement window  38 . In this embodiment, a spectroscope is suitable for the photodetector  82 . 
     In the  FIG. 10  embodiment, the illuminating light (polarized light) is emitted from the light source  24  so as to be parallel with the rotation symmetry axes of the first mirror  76  and the second mirror  78  (corresponding to the optical axes). Emitted light passes through a hole formed at the center of the first mirror  76  and reaches the surface of the living tissue  40 . The light interacted with the living tissue  40  is reflected by the second mirror  78  and the third mirror  80  and reaches the spectroscope (photodetector  82 ). The surface of the living tissue  40  is positioned at the combined focus of the first and second mirrors  76 ,  78  so that the position of the spectroscope of the scattered light reaches varies depending on the scattering angle. Furthermore, the scattered light becomes in parallel with the optical axis near the spectroscope. 
     The mirrors should be arranged so that the image point (of the virtual image) of the first mirror  76  when the object point is the combined focus coincides with the “focal point of the second mirror  78 ”. Where the first mirror  76  is a hyperboloid mirror and the second mirror  78  is a parabaloid mirror, optical aberrations may be reduced. 
     Turning now to  FIG. 11 , there is shown a schematic view similar to that of the  FIG. 10  embodiment, however, the optical axes of the mirrors are perpendicular to the outer layer of the capsule  10  and the measurement window  38  is a wedge-shaped transparent member. This embodiment enables the reduction of stray light coming through the measurement window  38  and eliminates the need for inclining the optical axes of the mirrors as in the  FIG. 8  embodiment, thereby simplifying the structure of the capsule  10 . 
     Turning now to  FIG. 12 , there is shown a simplified cross sectional diagram of the capsule  10  of the present invention and, to explain this embodiment,  FIG. 12  has been simplified with respect to  FIG. 2  for example, it being understood that the  FIG. 12  capsule  10  can have the similar components as described with respect  FIG. 2 . As such, the capsule  10  of  FIG. 12  includes the capsule  20 , the blood content detector  22 , the illuminating means  16 , the light receiving means  28  and the measurement window  38  that is shown to be contacting the living tissue  40 . 
     As explained, with the capsule, it is important that the device be in actual contact with the living tissue  40  in order to obtain a valid reading of the blood content in that tissue. In this embodiment, there is a contact detector that alerts the user when there has been actual contact between the capsule  10  and the living tissue  40  of the patient. As an alternative, there can be a proximity detector that senses the approach of the capsule  10  to the living tissue  40  and which includes a contacting predicting means that sends a command to the overall system to commence a measurement of the blood content in the living tissue  40  when the actual contact is imminent. As used herein the term “proximity detector” will refer to a detector that senses the nearing and imminent proximity of the capsule to the living tissue as well as where the proximity is to the point where there is actual contact between the capsule and the living tissue. 
     Accordingly, in  FIG. 12 , in one exemplary embodiment, there is a proximity detector that comprises a image sensor  84  such as a camera, and which is directed toward the living tissue  32  along a path that is generally proximate to the path of the illuminating directed toward that living tissue  32  by the illuminating means  16 . The image sensor  84  can receive the image of the living tissue  40  through the measurement window  38  or through an alternate window. The image sensor  84  includes an image analysis  86  that analyzes the image from the image sensor  84 . 
     Basically, when an image sensor gets too close to a target so as to contact that target, the entire captured image takes on a substantially single color range. In the case of living tissue, that color range is typically a red color and the phenomenon is referred to as “redout”. That image can, therefore, be analyzed in the image analysis  86  by comparing the signal value with the threshold for the average color of red. By such means, the system can detect the contact between the capsule  10  and the living tissue  40  of the patient. A signal can then be sent by the image analysis  86  wirelessly to enable the capsule  10  so that the light intensity of the illuminating means  24  can be intensified in order to obtain a reading of the blood content in that tissue, the actual contact having been verified. 
     As stated, when the redout condition is sensed, the light intensity of the illuminating means  24  is immediately increased so as to be a level sufficient for spectrometry and the measurement of the blood performed. After the measurement, the light intensity of the illuminating means  24  is rapidly returned to the pre-measurement value. 
     In another exemplary embodiment, the proximity detector may be a mechanical detector  88  located on the external contacting surface of the capsule  10  and the mechanical detector  88  can be sensitive to the mechanical contact between the capsule  10  and the living tissue  40 . Further alternative embodiments of a proximity sensor include an electromagnetic signal sensor  90 , a laser  92  and laser detector  94 , a piezoelectric device  96 , and an optical detector  98 . 
     As an alternate embodiment of an intensity detector, there can be a system for detecting the distance between the capsule  10  and the living tissue  40  such that the distance determination means can predict how long the capsule  10  will take to come into actual contact with the living tissue and the system can signal the measurement system to start the onset of a measurement at the moment of contact. 
     Turning to the graph of  FIG. 13 , taken along with  FIG. 12 , signals transmitted from the distance sensor are continuously monitored for determining the distance between the capsule and the living tissue. The graph plots distance (D) between the capsule  10  and the living tissue  40  versus time (t). As can be seen, as the time progresses, the distance is narrowed to the time t 1  which is the point that a distance-detecting processor has determined that the actual contact is imminent. Thus, at t 1 , the distance-detecting processor determines that the capsule will likely contact the living tissue before the next measurement of the distance according to the trend in the time axis, the processor commands the measurement system to start a measurement of the blood flow. Accordingly at time t 2 , the actual measurement is taken. 
     The timeline of all system operations can be adjusted so that the time for that command to the actual start of a measurement is completely equivalent to the expected time until the contact of the capsule with the living tissue. Controlling the measurement system in such manner enables the accurate measurement even while a capsule is in contact with the living tissue. 
     In fact, the experienced time of contact does not always match the time of actual contact. The system may therefore have a means of monitoring the measurement results and evaluating the measurement results for their applicability in subsequent steps based on the fluctuation among different sets of measurement data or by comparing the final results with a predetermined threshold. 
     When considering the degree of invasion and acceptability by a patient, a capsule measurement type of device is highly desirable, however, it must be accurate at the time it is used. It is possible to correct a spectroscopic error due to a production error in the production process (which means storing correction data in the capsule). However, it is not possible to cope with an error of spectroscopic measurement value due to an optical element caused by vibration during transportation and changes of spectroscopic characteristics of illumination over time. Therefore, it is of great importance that the capsule be capable of easily being calibrated right before use. 
     Turning, therefore, to  FIG. 14 , there is shown a schematic view of a calibration system that meets those requirements. In particular, the capsule  10  is covered by a protective cap  100  so as to maintain the sterile conditions of the capsule  10 . The protective cap  100  can be made of a transparent material that allows sterilizing gas to pass through but does not allow bacteria to penetrate. The protective cap  100  includes a white diffuser plate  102  that is disposed inside of the protective cap  100  so as to function as a calibration means. As can be seen, a beam of light emitted from the illuminating means  24  is diffused and reflected by the white diffuser plate  102  and directed to the light receiving means  28  and the Iw(λ) is measured and transmitted to the data processing means  58  ( FIG. 1 ) where it is used in the equations carried out therein. 
     Accordingly in this embodiment because the capsule  10  maintains the sterile condition with the protective cap  100  affixed thereto, a user can conduct calibration before using the device and then remove the protective cap  100  from a notch  104 , and can use the capsule  10  in a condition that is both sterilized and calibrated. 
     In addition, since a calibration means is provided inside the protective cap  100 , calibration can be carried out near the outer surface of the capsule  10 . Accordingly, because the quantity of the blood can be measured by making the outer surface of the capsule  10  come in contact with the living tissue of the patient, calibration can be carried out almost in the same state as an actual use thereof, thereby achieving highly accurate calibration. Furthermore, since a protective cap  100  and the white diffuser plate  102  are integrated into one unit, a user does not have to align the position of the calibration means with that of the capsule  10  so as to enable simple, easy operation. 
     Turning, finally to  FIG. 15 , there is shown a further exemplary embodiment of the calibration system of the present invention. In this embodiment, there is a container  105  that contains the capsule  10  and a white diffuser plate  102  is disposed within the container  105 . The container  105  is shown in the open position in  FIG. 13 . The container  105  has a recess  106  shaped like the outer shape of the capsule  10  and positioning can be accomplished by placing the capsule  10  within the recess  106 . 
     At least a portion of the protective cap  100  reached by the light emitted from light source  24  is made of a material that is transparent with respect to the wavelength of the illuminating light. As with the  FIG. 12  embodiment, calibration is carried out by use of the white diffuser plate  102 . 
     In this embodiment, the user carries out calibration before using the capsule  10  and, by removing the protective cap  100  from the notch  104  ( FIG. 14 ), and again the user has a capsule  10  that is both sterile and calibrated. 
     In addition, when compared to the  FIG. 14  embodiment, because the white diffuser plate  102  is disposed inside the container  104 , the material for that white diffuser plate  102  can be more widespread, thereby reducing the cost of the calibration system. A further advantage is that calibration can be carried out before the container  104  is opened which makes it possible that the effect of outside lights including room light, can be eliminated. 
     Those skilled in the art will readily recognize numerous adaptations and modifications which can be made to the of the present invention which will result in an improved device and method of using the same, yet all of which will fall within the scope and spirit of the present invention as defined in the following claims. Accordingly, the invention is to be limited only by the following claims and their equivalents.