Abstract:
A video imaging device includes a light source, a detector, and an optical polarization system for video imaging of superficial biological tissue layers. The device relies on taking a set of measurements at different polarization orientations so as to render a new image that is independent of the light reflected from the surface of a tissue sample and that is independent of the light scattered from deep tissue layers.

Description:
TECHNICAL FIELD 
     The present invention relates to a video camera whose images are based on polarized light to generate images from the first several hundreds of micrometers of superficial tissue layers below a tissue surface. This superficial region is where diseased tissue (pathology) usually arises in many tissues such as the skin, gastrointenstinal tract, lungs, reproductive tract, urinary tract, biliary tract, and inner lumen of blood vessels. 
     BACKGROUND OF THE INVENTION 
     The use of light in the ultraviolet-visible-near infrared wavelength range to image and characterize biological tissues is being widely pursued. These efforts have relied on several techniques. A first technique is absorption spectroscopy in which molecules electronically absorb certain wavelengths of light and hence attenuate the transmission or reflectance of that light to yield characteristic “absorption spectra”. A second technique is Raman spectroscopy in which molecules vibrationally absorb certain wavelengths of light, more in the infrared, and hence attenuate transmission yielding “Raman spectra”. A third technique is fluorescence spectroscopy in which molecules absorb certain wavelengths of light and re-emit longer wavelengths of fluorescence yielding characteristic “fluorescence spectra”. A fourth technique is scattering spectroscopy, in which photons of different wavelengths are scattered differently by cells yielding “scattering spectra”. 
     Motivated by a desire to better exploit scattering spectroscopy, this method of imaging concentrates the image contrast mechanism into the upper couple hundred micrometers of tissue. This superficial layer of tissue is the region where tissue pathology arises in many tissues. 
     One type of light used for imaging of materials is polarized light. Polarized light is strongly reflected off the surface of a material at the air/material interface. This reflectance depends on whether the polarized light is aligned “parallel” or “perpendicular” to the plane of the material. “Parallel” polarized light bounces off the material surface. “Perpendicular” polarized light penetrates into the material. This distinction between parallel and perpendicular alignment of polarized light is the basis of polarized lens in sunglasses which reject the parallel light reflected off a road surface. 
     Two approaches toward using this distinction between parallel and perpendicular light have been practiced. The first approach involves imaging material surfaces by selective acceptance of parallel polarized light. For example, polarized light has been used to detect “man-made” materials such as glass and metal within a field of “natural” materials such as trees, foliage, and organic soil. The second approach involves imaging material depths by selective rejection of parallel polarized light. For example, polarized light has been used to discriminate the skin surface from the skin depth. Illuminating the skin surface with parallel polarized light and viewing the skin by eye through glasses which are polarized parallel will emphasize the skin surface. Illuminating with parallel polarized light while viewing with glasses that are perpendicular polarized light will emphasize the tissue depth. In the latter case, there is always some parallel light which enters the skin but this light becomes randomly polarized by scattering within the tissue. Hence, viewing through perpendicular polarized glasses essentially rejects the surface reflectance and views the tissue depth with randomly polarized light. Imaging has been described that illuminates with perpendicular polarized light to achieve penetration of light into a tissue, then uses two wavelengths of light to enhance the contrast of a buried vessel based on absorption spectroscopy. Again, the image is based on light that penetrates deeply into the tissue and hence becomes randomly polarized. Viewing through an optical element which selects perpendicular polarized light offers a means of rejecting the glare of surface reflectance. 
     The task of identifying tissue pathology in the superficial tissue layers, however, is not served by either of the above. About 2-4% of the parallel polarized light is reflected by the surface. Such light does not interrogate the inner tissue where the pathology is located. About 91-93% of the reflected light is randomly polarized and is comprised of light that has penetrated deeply and been multiply scattered by the tissue. Such light is only a blinding artifact while attempting to observe the superficial tissues where pathology arises. Even observing the perpendicularly polarized light component of such multiply scattered deeply penetrating randomly polarized light does not discriminate light that scatters superficially from light that penetrated deeply. Only about 5% of the reflected light is not randomly polarized but is back-scattered by the superficial couple hundred micrometers of tissue. This invention provides a device to image based solely on that 5% of light that has penetrated the surface but not penetrated the tissue depth. 
     SUMMARY OF THE INVENTION 
     The present invention relies on taking a set of measurements using a broad illumination beam of light circularly polarized or linearly polarized at different angles of alignment and observing the tissue with a system that discriminates circularly polarized light and the various alignments of linearly polarized light. Also, a number of wavelengths of light are used to acquire images. The choice of wavelength may be made by the choice of light source or by including filters at either the source or camera detector. The wavelength dependence of polarized light scattering depends on the size distribution of tissue ultrastructure, i.e., cell membranes, protein aggregates, nuclei, collagen fibers, and/or keratin fibers. A set of images is taken with different combinations of source and collector polarization and wavelength. The images are then recombined to yield an image which rejects surface reflectance, rejects deeply penetrating light, and is optimally sensitive to just the light reflected from the superficial layer of the tissue. 
     The invention may include an optical element in contact with the tissue surface (e.g., a glass flat), an oblique angle of source illumination, and an angle of camera observation which differs from the angle of surface reflectance. The glass flat provides a tissue/glass interface that is well coupled and smooth such that oblique incidence of illumination light will cause surface reflectance to reflect at an oblique angle opposite the incident angle of illumination. The camera views the surface at an angle different from this angle of surface reflectance and hence no surface reflectance enters the camera. 
     For example, consider a system where linearly parallel polarized light is used for illumination and two images are acquired, one image selecting linearly parallel (Par) polarized light and one image selecting linearly perpendicular (Per) polarized light. The two images are recombined using the following expression: 
     
       
         New image=Par−Per  (Equation 1)  
       
     
     Each Par and Per image includes about 90% of the corresponding parallel or perpendicular component of randomly polarzied light from deeper tissue layers and these component are equal in magnitude. Hence, the difference Par−Per subtracts these common contributions from deep tissue layers. The surface reflectance (or glare) is rejected by the strategy of oblique incidence of illumination and the optical element in contact with the tissue to ensure glare is diverted from the camera. Hence the Par−Per image is based on the 5% of the total reflected light which is back-scattered from only the superficial tissue layer. 
     Another example of how to recombine polarized light images to achieve optimal sensitivity to the scattering by the superficial tissue layer is to reject any interference due to superficial pigmentation that absorbs light. For example, a doctor cannot see the superficial tissue layer beneath a freckle or beneath (or within) a pigmented nevus. The following expression is useful: 
     
       
         New image=(Par−Per)/(Par+Per)  (Equation 2)  
       
     
     The numerator as before selects the light scattered from the superficial tissue layer. The denominator provides a means of rejecting the influence of a superficial layer of absorption such as the melanin in the epidermis of skin. Melanin is the absorbing pigment of skin. Such melanin acts as a filter on the tissue surface. All light must pass this filter twice, once on entry and once on exit. This filter attenuation is a common factor in all images acquired. Hence, by taking the ratio in Equation 2, the common factor cancels. In the image, the melanin disappears. For example, a pigmented freckle will disappear or the pigment of nevi will disappear. Hence, one can visualize the polarized light scattered from the superficial tissue layer without interference from superficial pigmentation. 
     The present invention has also found that using incoherent light, as opposed to coherent laser light, allows images which are free from “laser speckle” which is the interference of scattered coherent light. Such speckle is an interference that confuses the imaging of the superficial tissue layer. Lasers with very short coherence lengths (&lt;&lt;100 μm) qualify as an “incoherent” light source for such imaging. 
     Accordingly, an object of the present invention is to provide a video imaging device capable of generating an image using light scattered only by the superficial layer of a tissue. 
     Another object of the present invention is to provide a video imaging device capable of rejecting light reflected from the surface (surface glare). 
     Yet another object of the present invention is to provide a video imaging device capable of rejecting light reflected from deep tissue layers (randomly polarized light). 
     Still another object of the present invention is to provide a video imaging device capable of using oblique illumination through an optical element in contact with the tissue surface and light collection at an angle that avoids surface reflectance at the air/element interface in order to achieve the rejection of surface glare. 
     Another object of the present invention is to provide a video imaging device capable of acquiring a set of images based on different combinations of circularly and linearly polarized light for illumination and collection. 
     Another object of the present invention is to provide a video imaging device capable of acquiring a set of images based on different choices of wavelength of light for either illumination or collection. 
     Another object of the present invention is to provide a video imaging device capable of recombining the acquired set of images. 
     Another object of the present invention is to provide a video imaging device capable of recombining acquired images in order to cancel the influence of absorbing superficial pigmentation. 
     Another object of the present invention is to provide a video imaging device capable of using incoherent light (or low coherence light such as light having a coherence length &lt;&lt;100 μm) for illumination to avoid laser speckle in images. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a schematic of the device of the present invention for use in topical imaging of the superficial layers of a tissue sample. 
     FIG. 2 is a flowchart of the process and calculations conducted by the device of the present invention. 
     FIG. 3 is a schematic of the device of the present invention using an imaging fiber bundle for use in internal imaging of the superficial layers of a tissue sample wherein the fiber bundle is positioned generally perpendicularly to a tissue surface. 
     FIG. 4 is a schematic of the device of the present invention using an imaging fiber bundle for use in internal imaging of the superficial layers of a tissue sample wherein the fiber bundle is positioned generally parallel to a tissue surface. 
     FIG. 5A is an image of a freckle seen with the naked eye. 
     FIG. 5B is an image of the freckle of FIG. 5A as created by the device of the present invention. 
     FIG. 6A is an image of a nevus seen with the naked eye. 
     FIG. 6B is an image of the nevus of FIG. 6A as created by the device of the present invention. 
     FIG. 7 is a photograph of a clinical prototype of the device of the present invention. 
    
    
     DETAILED DESCRIPTION 
     Referring to FIG. 1, a light source  2  is used to illuminate the tissue surface  12 . The preferred light source is an incoherent light source or a low-incoherence light source (coherence length less than 100 μm) generating the illumination light  4 . The light source  2  can generate light at one or more single wavelengths or bands of wavelengths either sequentially or simultaneously. The illumination light  4  passes through an optical element  6  which can filter or retard the light so as to modify the polarization of the transmitted light and/or can filter the light to pass a band of wavelengths. The preferred light source is an incoherent white light source such as a tungsten lamp. The optical element  6  is a combination of linear polarization filters and optical retarders, such as a quarter-wave plate or an electrically controlled thin-film liquid crystal retarder, which are aligned such that one of at least 7 types of polarized light are transmitted: randomly polarized light, horizontal or parallel or 90° linearly polarized light, vertical or perpendicular or 0° linearly polarized light, diagonal 45° linearly polarized light, diagonal −45° linearly polarized light, circularly left polarized light, and circularly right polarized light. All of these options are known descriptions of types of polarized light used in measuring the various elements of the Mueller matrix for describing how light transmits through a generic optical element which is well known in optics. It is believed that optical element  6  may also include a lens system. It is believed that optical element  6  can be implemented using holographic technology. The preferred embodiment of element  6  is a linear polarizer oriented parallel to the tissue surface  12 . 
     The light  8  that has transmitted through element  6  follows a direction  10  and illuminates the surface  12  of the tissue  14  at an oblique angle  16 . An optical element  18  in contact with the tissue provides good optical coupling to the tissue and a smooth element/tissue interface  20  which directs specularly reflected light  22  from the element/tissue interface away from the tissue at a new oblique angle  23 . Such specularly reflected light  22  has not entered the tissue and has not interrogated the subsurface tissue layers and is not used for imaging in this invention. The light that is not specularly reflected and enters the tissue is denoted as  24 . One portion  28  of the light  24  that enters the tissue is scattered by the superficial tissue layer  26 . The remaining portion  30  of the light  24  penetrates deeply into the deeper tissue layer  32 . The deeply penetrating light  30  is multiply scattered and becomes randomly polarized. A portion  34  of light  30  can scatter back up toward the camera system  36  but this light  34  is not used for imaging in this invention and will be rejected by subsequent algorithmic and arithmetic computations described later with regard to FIG.  2 . The superficially scattered light  28  is used for imaging because its interaction with the superfical tissue layer  26  provides optical image contrast optimally localized in layer  26  which is the site where tissue pathology often arises. The light  28  scattered from layer  26  escapes the tissue and propagates toward the detection camera system  36 . Both the light  28  and the light  34  pass through an optical element  38  before reaching the camera system  36 . This optical element  38  is the same as optical element  6  in terms of the variety of types of polarized light and band of wavelengths that can be selected for transmission, which was described above for element  6 . The choice of type of polarization for element  38  is independent of the choice of type of polarization for element  6 . The preferred embodiment of optical element  38 , which can be aligned in either a parallel or a perpendicular orientation, is a tunable liquid-crystal filter which can be electronically switched to pass different narrow bandwidths of light selected from the ultraviolet-visible-near infrared spectral range. The light  28  which transmits through element  38  is denoted  40  and the light  34  which transmits through element  38  is denoted  42 . The light  40  and the light  42  reach the camera system  36  to form an image. The algorithmic and arithmetic combination of a set of images can yield a new image (referred to as reference numeral  56  in FIG. 2) which is based on light  40  and rejects light  42 . The camera system  36  is described in FIG.  2 . The light denoted as  4 ,  8 ,  22 ,  24 ,  30 ,  28 ,  34 ,  40 , and  42  is illustrated as single dashed lines in FIG. 1 but the intention is to denote beams of light with some width and some degree of divergence or convergence. 
     Referring to FIG. 2, a flowchart describes the camera system  36  of FIG. 1 which consists of a camera  50  for detecting images, computer acquisition of a set of images  52 , schematically depicted as images  1  to n where n is greater than one, each made with different combinations of polarization settings for optical elements  6  and  38  and/or selections of wavelength for the light source  2  or the filter function of optical element  6  or  38 , image processing software  54  for algorithmic and arithmetic recombination of the image set  52  to yield a new image  56 , which is displayed on a video display  58 . The preferred embodiment would use two images in the image set  52 : (1) a parallel image (Par) based on a selection of parallel linearly polarized light by element  6  and parallel linearly polarized light in element  38  in FIG. 1, and (2) a “perpendicular” image (Per) based on a selection of parallel linearly polarized light by element  6  and perpendicular linearly polarized light in element  38  in FIG.  1 . This image set  52  is passed to the imaging process software  54  which computes pixel by pixel the following arithmetic combination of the two images: New image=(Par−Per)/(Par+Per), which is Equation 2 from above. This new image  56  is then displayed on a video display  58 . Other choices of images for the image set  52  and for the arithmetic operations  54  to yield a new image  56  are desirable and easily implemented. 
     In FIG. 3, an alternative embodiment is shown which is appropriate for endoscopic and laparoscopic applications. The light source  2  delivers light  4  which passes through an optical element  6  which is identical to element  6  in FIG.  1  and transmits a type of light  8  that has a selected type of polarization. Either the source  2  or the element  6  may have a selected choice of wavelength band or bands. The transmitted light  8  is coupled by a coupling system  68 , which may be a single lens or a lens assembly or some combination of lenses and mirrors or holographic device, into an optical fiber device  70  which is constructed with one or more optical fibers which are polarization-maintaining optical fibers that are common and commercially available. The light  8  that is coupled by coupling system  68  into fiber bundle  70  is denoted as  66  and is delivered by fiber bundle  70  to an optical element  72  in contact with the tissue surface  74 . 
     The element  72  consists of a means of directing illumination light  66  into a new direction  76  and the light in this new direction is denoted as  78  which obliquely illuminates the element/tissue interface  80  at an angle  82 . Element  72  may include an optical lens  84  to focus the light  66  from the fiber device  70  to yield light  88  which is deflected by a mirror  89  to yield light  78  at the desired direction  76  for illuminating the element/tissue surface  80 . It is believed that other embodiments using lens, mirrors and/or holographic devices can achieve the same purposes served by element  72  and its associated components  84  and  89  which are to obliquely deliver illumination light  66  along the direction  76  to the element/tissue interface  78  at angle  82 . The optical element  72  establishes an element/tissue interface  80  which specularly reflects light  86  at a new angle  93  and light  86  does not enter the tissue and is not used for imaging. The light not specularly reflected as  86  is denoted as  91  and enters the tissue. A portion of light  91  scatters from the superficial tissue layer  92  back toward the camera system  36  to yield scattered light  94  that is used for imaging. A portion of light  91  penetrates into the deeper tissue layer  96  and is denoted as  98  and becomes randomly polarized. A portion of light  98  is scattered back toward the camera system  36  and this portion is denoted as  100 . Light  100  is not used for imaging. The scattered light  94  and  100  are coupled by the optical element  101  into a second optical fiber bundle device  102 . The fiber bundle device  102  is an imaging optical fiber bundle composed of polarization-maintaining fibers which map the image entering the bundle to the an identical image exiting the bundle. Imaging optical fiber bundles are commercially available and can be implemented using polarization-maintaining optical fibers. 
     The optical element  101  may consist of a single lens, a lens assembly, or a holgraphic device in order to achieve proper focusing and coupling of the image from the scattered light  94  and  100  into the fiber bundle  102 . The image based on the scattered light  94  and  100  is carried by the fiber bundle  102  to a lens assembly  103  that focuses the light from fiber bundle  102  through an optical element  38  onto the camera system  36  to form an image. The optical element  38  which is the same as element  38  in FIG.  1  and selects one type of polarization for transmission. The light  94  that passes through element  38  has been filtered or retarded and is denoted as  40 , as in FIG.  1 . The light  100  that passes through element  38  has been filtered or retarded and is denoted as  42 , as in FIG.  1 . The amounts of light  40  and  42  that reach the camera system  36  depends on the choices of wavelength for the light source  2  or for the optical elements  6  and  38  and on the choices of types of polarization for optical elements  6  and  38 . The algorithmic and arithmetic combination of a set of images can yield a new image (referred to as reference numeral  56  in FIG. 2) which is based on light  40  and rejects light  42 . The camera system  36  was described in FIG.  2 . 
     FIG. 4 shows a system identical to FIG. 3 however the orientation of the fiber bundle devices  70  and  102  are oriented parallel to the tissue surface  74  and optical element  72 . All aspects of FIG. 4 have the same labeling as in FIG.  3 . The figure is drawn with a three-dimensional aspect to illustrate the parallel orientation of fiber bundles  70  and  102 , however the drawing is schematic in nature and the tissue  90  is shown two-dimensionally, exactly as in FIG.  3 . The coupling system  84  accomplishes the task of redirecting the illumination light  66  down onto the issue/element interface  80  at an oblique angle  82 , as in FIG. 3, coupling system  101  collects light  94  and  100  for return to the camera system (referred to as reference number  36  in FIG.  2 ). Such a configuration (fiber bundles  70  and  102  parallel to tissue surface  74  and optical element  72 ) is important when requiring side viewing of a tissue surface while the total system is inserted into narrow internal spaces of the body. FIG. 4 is in contrast to FIG. 3 which showed the fiber bundle devices  70  and  102  to be oriented perpendicular to the tissue surface  74  and optical element  72 . Such perpendicular configuration is often important when viewing a tissue surface for example when viewing the skin, the oral cavity, the stomach, and other surfaces best viewed from a perpendicular orientation. 
     FIG. 5A shows an image  104  of a freckle  106  on the skin  108  using randomly polarized light. FIG. 5B shows an image  110  of a freckle  112  on the skin  114  using the preferred embodiment described in FIG.  2 . FIGS. 5A and 5B show images of the exact same skin site. The melanin pigment of the freckle  112  appears to disappear in image  110  and shows nothing abnormal underlying the freckle. 
     FIG. 6A shows an image  116  of a pigmented nevus  118  on the skin  120  using randomly polarized light. FIG. 6B shows an image  122  of a pigmented nevus  124  on the skin  126  using the preferred embodiment described in FIG.  2 . The melanin pigment of the nevus  124  appears to disappear in image  122  and reveals a distinctive tissue structure in the superficial tissue layer. A doctor&#39;s eye cannot see the structure shown in image  122 . 
     FIG. 7 shows a clinical prototype  128  which was prepared and tested in a pilot clinical trial. The entire light source and camera assembly as described in FIG. 1 is denoted as  130  which is held on a universal joint  132  supported by a counter-balanced levered arm  134 . The entire system ( 130 ,  132 ,  134 ) along with the computer data acquisition and display system  136  is placed on a cart  138  which allows the prototype  128  to be mobile in the clinic.