MXPA01004555A - Method and apparatus for providing high contrast imaging - Google Patents
Method and apparatus for providing high contrast imagingInfo
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- MXPA01004555A MXPA01004555A MXPA/A/2001/004555A MXPA01004555A MXPA01004555A MX PA01004555 A MXPA01004555 A MX PA01004555A MX PA01004555 A MXPA01004555 A MX PA01004555A MX PA01004555 A MXPA01004555 A MX PA01004555A
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Abstract
An in vivo imaging device having an illumination system that creates a virtual source within a tissue region of a subject in a non-invasive manner. The illumination system transforms a maximum amount of illumination energy from a light source into a high contrast illumination pattern. The illumination pattern is projected onto the object plane in a manner that maximizes the depth to which clear images of sub-surface features can be obtained. The high intensity portion of the illumination pattern is directed onto the object plane outside the field of view of an image capturing device that detects the image. In this configuration, scattered light from within the tissue region interacts with the object being imaged. This illumination technique provides for a high contrast image of sub-surface phenomena such as vein structure, blood flow within veins, gland structure, etc.
Description
METHOD AND APPARATUS FOR PROVIDING HIGH-CONTRAST IMAGE FORMATION
BACKGROUND OF THE INVENTION
FIELD OF THE INVENTION The present invention is concerned with the image formation analysis. More particularly, the present invention is concerned with the use of imaging to perform non-invasive spectral imaging analysis of the vascular system of a subject.
RELATED TECHNIQUE The most widely accepted methods of blood tests and blood tests require invasive and in vitro techniques. For example, a conventional whole blood count that includes the differential test of white blood cells (CBC + Dif) is done in an "invasive" manner in which a venous blood sample is drawn from a patient by means of a needle and submitted to a laboratory for analysis. Alternatively, it is often necessary to measure other types of blood components, such as non-cellular constituents (eg, blood gases and bilirubin) present in the plasma component of the blood. The most common method for bilirubin analysis is through an in vitro process. In such an in vitro process a blood sample is extracted invasively to the patient.
REF: 129314 The elements formed (red blood cells and other cells) are separated by centrifugation and the remaining fluid is chemically reacted and analyzed spectrophotometrically. Invasive techniques, such as for testing
CBC + conventional Diff and bilirubin analysis, pose particular problems for newborns, elderly patients, patients with burns and patients in special care units. Thus, it is desirable to use a device that is capable of rapidly and quantitatively measuring invasively a variety of blood and vascular characteristics. Such a technique will eliminate the need to draw a venous blood sample to determine the characteristics of the blood. A device of this type will also eliminate the delay by the results of the laboratory in the evaluation of the patient. Such a device also has the added comfort advantage of the patient. Soft tissues, such as mucous membranes or unpigmented skin, do not absorb light in the visible and near infrared, that is, they do not absorb light in the spectral region where the hemoglobin absorbs light. This allows the vascularization to be differentiated by spectral absorption of the surrounding soft tissue fundus. However, the surface of the soft tissue strongly reflects the light and the soft tissue itself effectively disperses the light after a penetration of only 100 microns. Therefore, in vivo visualization of circulation is difficult due to poor resolution and in general not practical due to the complexities involved to compensate for the multiple dispersion and specular reflection of the surface. The resolution of such images is limited due to scattering of light and the calculations to compensate for scattering are complex. Spectrophotometry involves analysis based on the absorption or attenuation of electromagnetic radiation by matter at one or more wavelengths. The instruments used in this analysis are called spectrophotometers. A simple spectrophotometer includes: a radiation source such as, for example, a light bulb; a spectral selection means such as a monochromator containing a prism or grid or a colored filter and one or more detectors, such as, for example, photocells, which measures the amount of light transmitted and / or reflected by the sample in the spectral region selected In opaque samples, such as solids or highly absorbent solutions, the radiation reflected from the surface of the sample can be measured and compared with the reflected radiation from a non-absorbent or white sample. If this intensity of reflectance is plotted as a function of wavelength, it provides a spectrum of reflectance.
Reflectance spectra are commonly used to match colors of dyed fabrics or painted surfaces. However, due to its limited dynamic range and inaccuracy, reflection or reflectance spectrophotometry has been used mainly in qualitative analysis instead of quantitative analysis. On the other hand, transmission spectrophotometry is conventionally used for quantitative analysis because Beer's law (which is inversely related to the logarithm of the intensity measured linearly with the concentration) can be applied. Reflectance spectrophotometry is not a primary choice for quantitative analysis because specularly reflected light from a surface limits the available contrast (white to black or signal-to-noise ratio) and consequently, the range of measurement and linearity. Due to the surface effects, measurements are usually made at an angle with respect to the surface. However, only in the case of a Lambertian surface will the reflected intensity be independent of the viewing angle. The light reflected from a Lambertian surface appears equally bright in all directions (cosine law). However, good lambertian surfaces are difficult to obtain. The conventional reflectance spectrophotometry presents an even more complicated relationship between the intensity of reflected light and the concentration than that which exists for the transmission spectrophotometry that follows Beer's law. Under the Kubelka-Munk theory applicable in reflectance spectrophotometry, the intensity of the reflected light can be indirectly related to the concentration through the absorption to dispersion ratio. Several devices for in vivo analysis based on reflectance spectrophotometry have been developed recently. However, these conventional reflectance-based devices are less than optimal for several reasons. For example, one such device uses image analysis and reflectance spectrophotometry to measure parameters of individual cells such as the size of the cell. The measurements are taken only in small containers, such as capillaries, where individual cells can be visualized. Because this device takes measurements only in capillaries, the measurement made by the device will not accurately reflect measurements for larger vessels. Other devices use light application means that focus a source of illumination directly on a blood vessel in a detection region. As a result, these devices are extremely sensitive to the movements of the device with respect to the patient. This increased sensitivity to the device or movement of the patient can lead to inconsistent results. To counteract this sensitivity to movement, these devices require means of stabilization and fixation. Other conventional devices will do. been developed based on traditional dark champion lighting techniques. As understood in traditional microscopy, dark field illumination is a method of illumination that illuminates a sample but does not admit light directly to the objective. For example, a method of traditional dark field imaging is to illuminate an image plane in such a way that the angular distribution of illuminating light and the angular distribution of light collected by a lens for image formation are mutually exclusive. However, these devices are subject to the dispersion of the optically active tissue in the image path which creates a backscattering dependent on the orientation or image glare that reduces the image contrast. In addition, the rotation of these devices causes a change in contrast. Thus, there is a need for a device that provides an in vivo, non-invasive, complete analysis of the vascular system with high image quality. There is a need for a device that provides high resolution visualization of: cellular components of the blood (red blood cells, white blood cells and platelets); blood rheology; the vessels in which blood travels and vascularization throughout the vascular system. There is also a need for a device that can minimize glare and other detrimental artifacts that arise in conventional reflectance spectrophotometric systems.
BRIEF DESCRIPTION OF THE INVENTION The present invention is concerned with a method and apparatus for the analysis of a sub-surface object, such as blood or tissue beneath the skin of a patient, by the use of a high-contrast illumination technique. In one embodiment, the device includes a light source, a lighting system and an image forming system. The light source provides a beam of illumination that propagates along a path of illumination between the light source and the plane on which the object is located (the plane of the object). The lighting system transforms the illumination beam into a high contrast lighting configuration and projects the configuration or pattern of illumination onto the subsurface object. The lighting pattern or configuration has a high intensity portion and a low intensity portion. The image formation system includes ur. image capture device that detects an image of the sub-surface object. In accordance with the present invention, the image of the object is formed by the scattered illumination of the high contrast illumination pattern which is transmitted through the sub-surface object and propagates along an image path to the capture device. image. In addition, the high intensity portion of the illumination pattern is incident on the plane of the object to the outside of a display field of the image capture device. In a preferred embodiment, the device further includes a lighting pattern generator that transforms the illumination beam into a high contrast illumination pattern. In this mode, a relay lens projects the lighting pattern onto the plane of the object. In a further embodiment of the present invention, concealment is used to block a portion of illumination beam. Alternatively, a conical lens (also referred to as an axicon or truncated-conical mirror), a conical grid or a holographic optical element is used to generate a high-contrast illumination pattern. In a further aspect of the present invention, the apparatus includes crossed polarizers which act to prevent any polarized light reflected from the surface of the sub-surface object or reflected from the layer of birefringent tissue in the near field reaching the device for capturing image. A further aspect of the present invention provides a method for forming a light source in a sub-surface tissue region that contains an object of interest in a non-invasive manner. The object is illuminated around a plane of the object where the object is located and is detected by an image capture device. In a first step, a light source is provided. Next, the light from the source is transformed into a pattern or high-contrast lighting configuration that has a high-intensity portion and a low-intensity portion. The illumination pattern is directed onto a surface of the tissue region such that the high intensity portion of the illumination pattern is incident on the plane of the object to the outside of a display field of the image capture device. In accordance with the present invention, the high intensity portion of the illumination pattern suffers one or more scattering events in the tissue region. Next, the scattered light that interacts with the object is detected by the image capture device. In accordance with the present invention, a substantial portion of the scattered light is transmitted through the object thus providing an image of the object that is detected by the image capture device.
BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated in the present and form part of the specification, illustrate the present invention and together with the description, serve to explain the principles of the invention and to enable a person skilled in the relevant art to make and use the invention. In the drawings, similar reference numbers indicate identical or functionally similar elements. Additionally, most of the digits on the left of a reference number identify the drawing in which the reference number appears for the first time. Figure IA illustrates scattering events in the near field with standard reflectance spectrophotometry. Figure IB illustrates the lighting technique of the present invention; Figure 2 shows an image forming device having concealment according to an embodiment of the present invention;
Figure 3 shows a lighting profile in cross section in the plane of the object according to an embodiment of the present invention; Figure 4 shows an image forming device having a conical slow in accordance with one embodiment of the present invention; Figure 5A shows a detailed view of an axicon or frustoconical mirror; Figure 5B shows a detailed view of a conical diffraction grating; Figure 5C shows a conical grid having a diffraction surface profile; Figure 6 shows a pattern or configuration of annular image on the surface / field lens; Figure 7 shows a trace of rays of a light beam in an image beam according to an embodiment of the present invention; Figure 8A shows an image forming device having an improved collapsible mirror according to an embodiment of the present invention; Figure 8B shows an approaching view of the improved folding mirror according to the present invention; Figure 8C shows exemplary measurements for the folding mirror of the present invention;
Figure 8D shows an exemplary incident lighting pattern on the plane of the object according to the present invention; Figure 9 shows an exemplary image of the vascular region of a patient taken by a device of the present invention; Figure 10 shows an exemplary image analysis method of the present invention; Figure 11 shows a block diagram of a computer system suitable for use in the present invention and Figure 12A and 12B show embodiments of the present invention suitable for use with a subject.
DETAILED DESCRIPTION OF THE MODALITIES General Description The present invention is concerned with a method and apparatus for the analysis, in particular for the non-invasive in vivo analysis of the vascular system of a subject. In particular, the device and method of the present invention provide a means for creating a virtual illumination source from within the region of the living tissue surrounding ur. Blood vessel or tissue area that is imaged, resulting in the present invention uses transmission, rather than reflection, for the images that are analyzed.
Terminology In order to form an image, two criteria must be met. First, there must be an image contrast resulting from a difference in the optical properties, such as absorption, refractive index c dispersion characteristics, between the subject to be formed in the image and its surroundings or background. Second, the light that is collected from the subject must reach an image capture medium without substantial distortion, that is, the image must be captured from a depth that is less than the multiple scattering length. As used herein, "image" refers to any image that satisfies the two above criteria. The resolution required to capture the image is determined by the spatial homogeneity of the portion formed in the image. For example, an image of individual cells requires high resolution. An image of large vessels can be made with low resolution. An appropriate image to make a value-based determination requires very low resolution. The tissue covering the portion formed in the image is thus preferably light-transparent and relatively thin, such as the mucosal membrane inside the iaeics of a human subject. As used herein, "light" generally refers to electromagnetic radiation of any wavelength, in which the infrared, visible and ultraviolet portions of the spectrum are included. A particularly preferred portion of the spectrum is that portion where there is relative transparency of the tissue, such as in the visible and near infrared wavelengths. It will be understood that for the present invention, light can be coherent light or incoherent light and illumination can be stable or in pulses of light. The present invention utilizes a lighting technique to transform a lighting beam into a pattern or configuration of high contrast illumination. This pattern or configuration of illumination is one in which the illuminated region of the image plane formed each time completely out of the field of view of a target of the image formation system. In a preferred embodiment, the illumination pattern has both a low intensity region (preferably in its central region) and a high intensity region (preferably in its external region (where the high intensity region makes an impact with the plane) of the object to the outside of the objective display field of the image forming system A ring or light ring is an exemplary high contrast illumination pattern described herein The device of the present invention can be attached to the formation of image and analysis of large vessels, small vessels and capillary plasma As used herein, "large vessel" refers to a vessel in the vascular system of sufficient size such that a plurality of red blood cells flow side to side through it, "small vessel" refers to a vessel in the vascular system of a size such that the red blood cells flow substantially in "a single f ila "through it. To implement the method of the present invention, a light source is used to illuminate the region surrounding the portion of the vascular system of the subject to be imaged, such as a blood vessel or tissue sample. The light emanating from the image is captured by means of image capture. "Image capture means" means a device capable of capturing an image as defined herein. Suitable image capture means include, but are not limited to, a camera, a film medium, a photosensitive detector, a photocell, a photodiode or a camera with charge coupled device
(CCD). A means of image correction and analysis, such as a computer, is coupled to the image capture means for carrying out image correction, scene segmentation and analysis of the characteristics of the image. The "depth of penetration" or length of the path for the illumination light is controlled by at least three parameters: (1) the wavelength of light;
(2) the size and density of the particles with which the light interacts and (3) the Refractive Index. Normally, if the wavelength of the light, the particle size and density and the refractive index are constant, then the depth of penetration is constant. Therefore, a measurement made per unit area in such an image is proportional to a measurement per unit volume because the depth of penetration is constant. An area measurement is a volume measurement with a third dimension
(depth) constant. Note that the depth of penetration may vary locally with the structure of the tissue, based on the above parameters. Crossed polarizers are also preferably used to implement the present invention. A polarizer is placed in the path of light between the light source and the illuminated portion of the subject's vascular system. A second polarizer or "analyzer" is placed in the image light path between the illuminated portion and the image capture means. The second polarizer has a polarization plane substantially orthogonal to the polarization plane of the first polarizer. The cross-paired configuration improves the collection of light that has interacted with the illuminated portion of the vascular system and tissue of the subject to eliminate the light that has simply been reflected and has not fully interacted with the patient. illuminated Therefore, the light that has no information concerning the illuminated subject is eliminated. In this way, the image contrast is extensively increased, thereby improving the visualization in the illuminated portion.
SPECTROPHOTOMETRY OF REFLECTANCE As mentioned above, several conventional in vivo imaging devices have been developed based on reflectance spectrophotometry. Conventional reflectance spectrophotometric imaging devices are frequently based on Lohler type illumination (see W. Smith, Modern Optical Engineering, Me Graw Hill, Inc. 2nd Ed., Especially page 229 (1990), incorporated by reference in the The Kohler illumination comprises a light source that is imaged by a high numerical aperture condenser lens to an aperture stopper or obstacle of an objective lens.The illumination propagates through the objective to the plane of the object in question. This is due to the fact that this plane is the location or location of the pupil to the lighting system, commonly a polarizing beam splitter or a folding mirror with half Silver is used to bring the matching illumination to the optical axis of the image forming lens after being reflected from the splitter. az, the light from the source of illumination propagates along the same optical path as the light that forms the image. The light of the optical illumination elements propagate to a region of tissue that is visualized, while the image-forming light is scattered from the region of the tissue and propagates outwardly towards an image capture medium. In order to provide high quality images, the illumination light, which is reflected specularly from intermediate optical surfaces due to Fresnel reflection can be extinguished from the image formation path by the use of a cross-polarizer analysis in front of the means of image capture. Nevertheless, diffusely scattered light of for example, the walls of the lens case and optical assemblies, is not completely extinguished. This is due to the fact that diffusely scattered light is randomly or randomly polarized, 50% is aligned to pass through the scanning polarizer in front of the image capture means. Another source of dispersion originates in the region of the living tissue that is visualized. Living tissue is highly dispersing, structured, inhomogeneous and non-uniform. This non-uniformity in the tissue structure leads to birefringence. The birefringent nature of the tissue may interfere with the optimal performance of conventional in vivo imaging devices based on reflectance spectrophotometry. In these devices, the tissue covering the image forming portion must be traversed by the light to obtain a reflected image without multiple scattering. Then the reflected image is obtained from a single scattering of the reflected light. As such imaging devices using crossed polarizers, such as the "brightfield" image forming device described in the co-pending US patent application and assigned in common, serial No. 08 / 860,363 (filed on June 5, 1996) (hereinafter referred to as the '363 application and incorporated by reference herein in its entirety) may still provide less than optimal image quality due to the birefringent nature of the fabric. In addition, living tissue contains optically active substances such as glucose and collagen which causes a rotation of the polarization axis of incident light. The angle through which the polarization vector is rotated is a function of the propagation length in the optically active tissue.
The light that is incident on the tissue is dispersed when there are surfaces and diffuse substances such as pigment in the skin, hemoglobin in the cells of the blood, nucleus of cells, ligaments and muscles. Particularly suitable tissues are mucous membranes entrained in a variety of places in a human subject, such as the larynx, mouth, conjunctiva, rectum and vagina. Alternatively, for a premature baby, the skin itself is appropriately transparent to light. The tissue under the tongue and in the lip area has less dispersion and has more blood veins near the surface than most other parts of the body. Therefore, the region of the lip and tissue under the tongue are ideal areas for observing sub-superficial vascular phenomena. However, even in these areas, the depth at which they can make subsurface observations is limited due to the large number of structures and inhomogeneous nature of the tissue. It is generally difficult to image at depths greater than 400 microns (mm) in any tissue, even under the tongue or lip with any system. When used for in vivo imaging, the Kohler illumination system undergoes changes in contrast and changes in backlight levels caused by the rotation of the instrument with respect to the region of the tissue that is observed. The depth at which the instrument observes or "sees" in the tissue varies, with the site and with the orientation of the sample. These effects are caused by the distributed polarization rotation caused by glucose, protein and collagen and birefringence in the tissue. The nature of the illuminator axis also tends to allow "glare" light and direct specular reflections back to the image capture device. The tissue is birefringent due to the fact that living cells are not symmetric spheres or rectangles, uniformly packed. The birefringence represents a net difference in the refractive index in different directions. This is due to the difference in the refractive indices of cell walls, the cytoplasm and any interstitial fluids and the asymmetric nature of living cells. The effective refractive index is weighted by the propagation light in the medium and the refractive index of each component as follows:? Eff =? ru * Lx / S L? where r |? = index of refraction of the ies? m component length of the ies? mo component The cellular structure varies throughout the body and locally in areas such as the underside of the tongue.
Some areas have long thin muscle cells, which tend to be birefringent since the refractive index of the cell walls is different from that of the cytoplasm and interstitial fluids. In one direction, the electric field vector of the incident light is aligned with the long axis of the cell walls (and the effective refractive index is closer to the refraction limit of the cell wall) while in the other direction the vector The electric field spends a larger fraction of its time in the cytoplasm in the cell and in the interstitial fluids as they propagate. The amount of birefringence varies as a function of position in the tissue since the cellular structure varies with function. The birefringence may vary both in the phase and in the direction of the incident light. Another factor that contributes to poor image quality is the optical activity dependent on the propagation length of certain biological molecules such as glucose, collagen and certain proteins. These biological molecules cause a rotation of the electric field vector that is proportional to the propagation length in the media and to the concentration of the molecules. This length-dependent rotation of polarization allows some light that is subject to specular reflection of features to the interior (such as cell walls) to be transmitted through the image plane, since at some penetration depth, the incident light polarization vector will be rotated by 90 ° as it is in the tissue thereby allowing it to pass through the analysis polarizer. These two effects combine to allow any reflected light of arbitrary and varying depths within the tissue to propagate to a detector plane of the image capture means without being dispersed within the tissue. The variation in the amount of reflected light image and the depth from which it is reflected causes a change in contrast of the images that is directly related to the orientation of the sample. In accordance with the present invention, a system that is insensitive to the rotation of the instrument and the angle of incidence of the illumination will be more accurate and will provide more repeatable reading of any parameters that are measured.
Dispersion in the Fabric The interaction of light with matter is characterized by scattering theory. When an electromagnetic wave hits an atom or molecule it interacts with the electron bond cloud, imparting energy to the atom. The removal of energy from an incident wave (that is, incident light) and the subsequent re-emission of some portion of that energy is known as scattering. This fundamental physical mechanism operates in reflection, refraction and diffraction. For a general discussion of scattering, see Hecht and Zajac, Optics, 4th Ed., Addisson and Welsey (1979), especially chapter 8 (incorporated herein by reference). For example, reflected light can be characterized as having three distinct components. The first component is a "mirror or specular reflection" that presents the image of the source in a reflection. The second component is a "rough surface dispersion" component. The rough surface dispersion component is scattered light that is scattered by a rough surface and does not preserve the image of the source. However, both the mirror reflection component and the rough surface dispersion component retain the polarization. The third component is a "small particle dispersion" component commonly known as a "Raleigh dispersion" component. The Raleigh scattering component is light that is scattered by particles that are small compared to the wavelength of the illuminated light. The Raleigh scattering depolarizes the light. Accordingly, the Raleigh scattering component is the only component of reflected light that is depolarized in such a way that the original polarization is lost. Commonly, the light must undergo more than one scattering event (usually at least three) to completely change the polarization. For in vivo systems, depolarized light is used to form images, such as the device described in the '363 application, the birefringent nature of tissues can lead to less than optimal images. Figure IA is a simplified illustration of how the dispersion of an optically active or birefringent tissue layer can interfere with the optical quality of an image. In this illustration, an image forming device involves forming the image of a blood vessel of interest that is located within a region of tissue beneath the skin of a subject. The blood vessel of interest is shown as a cross section of the blood or capillary vessel 106. En. this system based on conventional reflectance, the illumination beam is directly incident on the capillary 106 and is within the display field 116 of a detector 114. For example, a lighting source (not shown) provides a light beam, illustrated by the light beam 102, to illuminate the capillary 106. The light beam 102 is polarized in the S direction. When the light beam 102 strikes the surface 104 of the skin, one or more of the interactions of the skin may be presented. dispersion mentioned above. For example, if the light beam 102 is subjected to a single specular reflection or rough surface dispersion, the reflected beam will maintain its polarization in the S direction and be extinguished by the analyzer 112, which only passes the polarized light P. other words, any polarized light S reflected from the skin layer 104 will not reach the detector 114. If the light beam 102 is not absorbed by or reflected by the skin layer 104, the light beam 102 will probably suffer one or more events of dispersion within the tissue region. For example, Figure IA illustrates the transmitted light beam that undergoes three scattering events (events (1), (2) and (3)). As mentioned in the previous section, there may be a dentrp layer of the tissue region that is weakly birefringent or diatenuating. This can be especially problematic if the superficial birefringent layer, such as layer 108, is located between capillary 106 and detector 114. In other words, the birefringent layer is located in the near field, which is the region directly in front of the blood vessel. of interest
(for example capillary 106) that lies within the image path. In general, when polarized light passes through a birefringent material the polarization vector is rotated through some angle? F.
For purposes of this description, the trajectory of the image is defined by the path that originates in the blood vessel of interest and ends in the detector. Note also that for this example, optical collection elements, such as objective lenses, are not illustrated in Figure IA for simplicity. In this example, the light beam 110, which is at least partially polarized in the P direction, will be reflected from the layer 108, transmitted through the analyzer 112 and detected by the detector 114. This type of reflected light signal acts as "glare" and impacts the quality of the image obtained by the detector 114. According to the present invention, this type of parasitic "dazzling" signal is greatly reduced (and the image contrast greatly improved) if the blood vessel of backlit interest instead of directly illuminated. In addition, according to the present invention, this feedback can be created by the non-invasive means. Figure IB is a simplified illustration of how the method and device of the present invention create a virtual source force of depth within living tissue. In this way, light is diffused through the blood vessel or tissue region of interest. The blood vessel is in turn backlit effectively, providing a maximum contrast of the image to the detector. In addition, the amount of light emanating from the near field is greatly reduced. Figure IB illustrates an environment similar to figure 1A. An important change is that the illumination beam, characterized in that the light beam 103, is incident on the surface 104 of the skin to the outside of the display field (FOV) 116 of the detector 114. In addition, the illumination beam is not directly incident on capillary 106. Even if there is a birefringent layer 108 in the near field of the tissue region, it is unlikely that the scattered and reflected light from layer 108 will depolarize. This is shown by the light beam 113. The light beam 103, which is initially polarized in the S direction, is directed to a region outside the display field of the detector 114. As the light passes through the layer 108, loses its pure polarization S and gains a polarization component P. As it disperses from the deeper areas of the tissue region, the illumination beam inevitably becomes a random mixture of polarization S and P. , the illumination light can be scattered or reflected from the depth inside the region of the tissue (that is, to a depth greater than the depth of the blood vessel that is formed in the image). Inevitably, a portion of this light represented by the light beam 111 is transmitted through the capillary 106. The polarization component P of the light beam 111 is transmitted by the analyzer 112 and is captured by the detector 114.
High Contrast Illumination Device and Method The present invention consists of a device and method that provides a high efficiency illuminator for in vivo investigations of the function of blood vessels and tissue. The ability to form an optically deep image to living tissue allows applications such as the measurement of blood parameters, counts of red and white blood cells, platelet counts, hemoglobin and hematocrit concentration. The present invention uses an illumination technique which depends on a maximum amount of illumination energy from a light source to an object plane in such a way that clear images of the subsurface characteristics can be obtained. The device of the present invention forms a high contrast lighting pattern or pattern, wherein the illumination dispersed in a ring of light around the region of the tissue under test that is outside of the field of view of a CCD camera or detector (or its objective lens). Other lighting patterns or configurations, such as non-annular configurations, may also be used to form the image of the tissue region or test as would be apparent to those of skill in the art given the present disclosure. The high contrast lighting configuration pattern of the present invention can be created in several different ways. First, a concealment can be placed in the path of the illumination beam. Secondly, an optical element, referred to as "axicon" or "truncated cone-shaped mirror" can be placed in the path of the illuminating beam. An "axicon" or truncated-conical mirror is an optical element that collects all the light that emanates from the light source and directs the light to a ring configuration in the far field. Third, in a similar way, a conical diffraction grating or a hologram can also be used instead of the truncated-conical mirror. Due to the multiple scattering events encountered by the illumination beam as it propagates through the region of tissue under test, the diffuse light from the outside of the field of view (FOV) of the image capture means of the present invention will illuminate the region of tissue under test (which is inside the FOV of the image capture means). According to the present invention, the scattered illumination will be evident from above and below the area of interest since the scattering 1
it is presented in the whole illuminated volume. Accordingly, the distribution of image intensity on the image forming means will have both scattered light has been reflected from the deeper (ie, backscattered) layers and transmitted through the blood vessels as well as scattered light reflected from the upper surface of blood vessels. Also, when using the device and method of the present invention, undispersed, unreflected light is incident on the image capture means because all of the reflected light directly is outside the FOV of the image capture means and its corresponding objective and thus can not be captured within the numerical aperture of the objectives of the image capture means.
PREFERRED MODALITIES OF THE PRESENT INVENTION The present invention is described in terms of several exemplary embodiments. The description in these terms is provided for convenience only. The invention is not intended to be limited to the application in these embodiments. Indeed, after reading the present description, it will be evident to a person experienced in the relevant technique (s) how to implement the present invention in alternative modalities.
to. First Mode The first embodiment of the present invention is a device (or in vivo apparatus) provides a high contrast illumination pattern or pattern is projected onto a tissue region of a subject in order to provide an image of blood vessels , blood flow or the tissue contained in it. The live apparatus comprises a light source, a lighting system and an image forming system. The image formation system includes an image formation detector and its objective. The illumination system provides a beam of illumination is used to illuminate a particular blood vessel or tissue area (referred to as the "object") of a patient or subject. The beam of illumination propagates along a path or segment called the path of illumination. The detector receives the light emanating from the object. This light is also referred to as the image beam. The path or segment the image beam travels is referred to as the image path. According to the present invention, the in vivo apparatus can be designed in such a way the illumination beam and the image beam share a common optical axis through a single objective, thus forming a coaxial system. Their axes can be combined using a beam splitter. In a preferred embodiment, an annular, linearly polarized illumination source is projected onto the objective plane of an image forming reflection spectrophotometer. It is only necessary the extension of the projected source completely fall outside the clear FOV of the image capture means along the image path or segment of the apparatus in vivo. The annular light source can be produced by the image formation of a circular seal placed in the path of a Kohler lighting system since all the incident light is outside the FOV, the light formed in the image must proceed from the depth inside of the tissue as discussed above in the dispersion section. In a preferred embodiment when using cross polarization in illumination and image formation, the image beam must come from multiple scattering events. The effect of this arrangement on this system is to produce true background illumination: the light source is effectively moved to a region behind the plane of the object in a non-invasive way. Figure 2 shows a block diagram illustrating one embodiment of an apparatus 200 for non-invasive in vivo analysis of the vascular system of a subject. The apparatus 200 includes a light source 202, a relay lens 208, a detector 260 and a target 217. The light source 202 illuminates a tissue region of a subject (generally shown as 223). Although a light source is shown in Figure 2, it will be understood that the present invention is not limited to the use of a light source and more than one light source can be used. In a modality where more than one light source is used, each light source can be monochromatic or polychromatic. The light source 202 may be a light capable of being pulsed, a non-pulsed light source that provides continuous light or a capable one of either type of operation. The light source 202 may include for example a light or pulsed xenon arc lamp, a light or mercury arc lamp, a light or halogen lamp, a light or tungsten lamp, a laser, a laser diode or a light-emitting diode (LED). The light source 202 can be a source for coherent light or a source for incoherent light. The light source 202 is collimated by a collimator lens or capacitor 204. The optical and physical characteristics of the collimator lens 204 depends on the type of light source that is used and the type of image to be projected onto an object 224. The Optical characteristics of the collimator lens 204 include its length 5
focal, numerical aperture and number f (f / #). The physical characteristics of the collimator lens 204 include its type of material (glass, plastic, etc.) and shape. Appropriate parameters will be apparent to one of skill in the art based on the present disclosure. For example, if a halogen lamp is used as a light source 202, the collimator lens 204 may comprise a spherical lens Fl with a focal length of the order of 5 millimeters (5 mm). The lens can be made of standard BK7 glass, which is transparent in the visible region of the electromagnetic spectrum, in addition if a lamp is used as the light source 202, a retroreflector (not shown) can be used to collect and reflect the light that emanates the rear portion of the lamp towards the collimator lens 204. In accordance with this embodiment of the invention (also referred to herein as "concealment mode"), a high contrast illumination pattern is projected onto the object 224 as follow. An occultation 205 is placed in the illumination path to transform the illumination emanating from the light source 202 into a high contrast illumination pattern. The illumination path, represented in the present as trajectory 206, is the light path that originates in the light source 102 and continues over the object 224.
In a preferred embodiment, the concealment 205 is located in the opening or obstacle 221. In this embodiment, a circular concealment is used. The concealment 205 blocks a predetermined portion of the incident light beam. The portion of the illumination beam not blocked by the concealment 205 continues to propagate along the illumination path. The remaining illumination beam 206 resembles an angle or ring of light with a dark central region. This configuration has its darkest point (that is, lower intensity) in its central region and higher intensity near the edges or edges of the configuration or pattern. Other appropriate types of concealments, in which. non-circular occultations are included, will be evident to those of experience in the art given the present description. A lens 208 (also referred to as relay lens 208) projects the high contrast illumination configuration onto a plane 219 of the object. The plane of the object in the present is the plane that is perpendicular to the image path, shown in the present as path 207, while the object 224 is located. In Figure 2, the plane of the object is illustrated by the plane 219. In a preferred embodiment, the optical parameters that define the. Projection lens 208 can be chosen according to those used in a Kohler lighting system. In the Kohler illumination, the opening of the source (in the present obstacle or retainer 221) is formed in image or projected onto the plane of the object. In this embodiment of the present invention, since the obstacle 221 is projected onto the plane 219 of the object, the high-contrast lighting pattern or pattern is also projected onto the plane of the object. In the apparatus 200, the projection lens 208 is designed to form the image of the high contrast illumination configuration on the plane 219 of the object and to form the image of the light source 202 between the objective of the image forming system , shown herein as the target 217. Thus, in a preferred embodiment, the apparatus 200 provides for a collimated light ring to be incident on the skin surface 222. For example, Figure 3 shows a measured illumination profile for a configuration of exemplary lighting projected on the plane of an object. The graphic illumination profile the relative intensity of the illumination signal as the function of the distance of the image axis. Thus, the high-contrast illumination pattern of this modality has its lowest intensity at the medium and highest intensity near the edges of the pattern. For example, the device of the present invention produces a merit figure of about 400 to 1. This merit figure represents the illumination intensity ratio of the outer portion of the annular pattern compared to the dark dot in the central region. Referring again to Figure 2, a folding mirror or beam splitter 218 is used to form a light path-between the light source 202 and the subject 224. In accordance with one embodiment of the present invention, the light splitter beam 218 is a coated plate having 50% reflection of the illumination beam 206. Other beam splitter modes 218 are discussed later herein. In a preferred embodiment, a first polarizer 210 can be placed between the light source 202 and the subject 224. The first polarizer 210 polarizes the light from the light source 202. A second polarizer or analyzer 220 can be placed between the object 224 and the image capture means 260 along the image path 207. The polarizers 210 and 220 preferably have polarization planes oriented substantially orthogonally (or 90 °) to each other. Polarizers, such as polarizers 210 and 220, which have polarization planes oriented 90 ° to each other are referred to herein as "crossed polarizers". As mentioned above, when the polarized light passes through a birefringent material, the polarization vector is rotated through an angle? F. In a cross polarizer system, as described in this preferred embodiment, the change in intensity is proportional to cosine2 (? F). The efficiency of a polarizer is a function of the percentage of the light introduced that is transmitted through the polarizer. For each unit of unpolarized (randomly polarized) light introduced to a polarizer, a perfectly efficient polarizer would transmit 50% of the light introduced. When randomly polarized light is introduced to two perfect polarizers (regardless of efficiency) configured as crossed polarizers, all light is extinguished, that is, no light is transmitted through the second polarizer. The more light that is extinguished by the crossed polarizers (that is, less randomly polarized light that is transmitted through the crossed polarizers), the greater the extinction of the crossed polarizers. Cross polarizers that have an extinction coefficient of at least 10"3 (for each unit of polarized light randomly introduced to cross polarizers, 1/1000 is transmitted through the crossed polarizers) are suitable for use in the present invention Appropriate cross polarizers are available as laminar polarizers from Polaroid Corp., Massachusetts.
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In one embodiment of the present invention, the light source 202 is itself a source of polarized light, for example, a laser or a laser diode, such that a separate first polarizer 210 is not required. The second polarizer 220 has a polarization plane oriented 90 ° in relation to the polarization plane of the source 202 of polarized light. In another embodiment, the beam splitter 218 is a polarized beam splitter. For example, in this mode, a divider cube of polarizing has been used in conjunction with a linear polarizer at the source. A polarizing beam divider cube transmits almost all of a polarization and reflects almost all of the polarization oriented at 90 ° to it. Polarization beam splitters are known in the art and can be purchased from various vendors of commercial optical components. This polarizing beam splitter can be aligned to ensure that all the light incident on the beam splitter cube is of the same polarization that will be reflected. This minimizes the lost light in the apparatus, which would pass through the beam splitter cube and finally degrade the signal to noise figure in the captured image. However, the selectivity of the polarizing beam splitter cube is a function of the angle of incidence of light at the interface and the numerical aperture of the optical components. As the illuminating beam converges or diverges, the reflectance of the beam splitter over the full aperture decreases. Similarly as the field angle increases the reflectivity found by the displaced portions of the beam axis also decreases. Preferably, the image of the object 224 emanates from a depth less than a multiple scattering length and travels along an image path 207 to the image capture means 260. However, the image forming system of the present invention can also capture images formed of a depth greater than a multiple scattering length. In target 217 it is used to amplify the image of object 224 on image capture means 260. The objective 217 is placed coaxially in the illumination path 206 and the image path 207. Image capture means 260 are placed in an amplified image plane of the objective 217. The objective 217 may comprise one or more optical elements or lenses, depending on the space requirements and image formation of the apparatus 200, as will be apparent to one skilled in the art based on the present description. Suitable image capture means 260 include those devices suitable for capturing a high resolution image as defined above. The image capture means capture all or part of an image for analysis purposes. Associated image capture means include, but are not limited to, a camera, a film medium, a photosensitive detector, a photocell, a photodiode, a photodetector or a charge device camera. For example, video cameras and cameras with charge-coupled devices (CCD) that have a resolution of 640 x 480 pixels and a frame rate of 300 Hz can be used. A particularly preferred image capture means is a Sony ICXL model CCD camera. Image capture means 260 can be coupled to image correction and analysis means 280 to perform image correction and analysis (explained later in the image analysis section). The resolution required for the image capture means may depend on the type of measurement and the analysis that is carried out by the in vivo apparatus. For example, the image resolution required to determine the concentration of hemoglobin (Hb) is less than the image resolution required to make cellular measurements, such as MCV or cell count. For example, measurements of hemoglobin concentration can be carried out using photocells, such as a red filter photocell and a green filter photocell, as the image capture medium.
Preferably, objective 217 may be one or more lenses that are selected with the lowest amplification level required to display the illuminated object. The required magnification is a function of the size of the object in the illuminated tissue that is to be displayed, along with the size of the pixels used for the image. For example, low amplification provides a high depth of field, but more imperfection to the image. High amplification provides low depth of field, but is more susceptible to blurring caused by movement. Blood vessels in the microvascular system are commonly 10-40 microns (μm) in diameter. From 10 to 20 (10-20) pixels per diameter of blood vessel provide an adequate image with a 10X lens. Less amplification can be used with pixels of smaller size. As mentioned above, according to a preferred embodiment, the illumination path 206 and the image path 207 share a common axis. The coaxial nature allows objective 217 to be used for more than one purpose. First, the target 217 acts as the target for the image capture means 260. In other words, it picks up the image beam exiting the object 224 on the image capture means 260. Second, the objective 217 acts to focus the image. High-center lighting pattern on the plane of the object. As mentioned above, the high intensity portion of the illumination beam 206 is directed to the outside of the FOV of the image capture means 260. The combination of the optical characteristics of the objective 217 and the image capture means 260 determine the FOV of the device 200. The FOV of the image capture means can be limited by many parameters including the numerical aperture of its objective (here the objective 217), the entrance pupils, the exit pupils and the area of the detector comprising the means of image capture 260. In objective 217 may comprise a single lens or multiple lenses. The physical and optical parameters of the objective 217 (e.g., lens material, numerical aperture, focal length, etc.) can be selected according to the desired image formation parameters. Normal targets are available from most commercial optical component vendors, which include Melles Griot and Newport Corp., both from California. The optical and physical characteristics, specific to objective 217 will be apparent to those of ordinary skill in the art, given the present disclosure. In another embodiment, the image separation means, such as a second beam splitter (not shown) can be used to separate the image of the object 224 into two or more image portions. Each image portion can be captured by a respective image capture means, such as image capture means 260. In addition, a spectral selection means such as a grid, filter and / or monochromator (not shown), is also it can be placed in the image path 207 between the second polarizer 220 and the image capture means 260. The spectral selection means can be, for example, a monochromator, a spectral filter, prism or grid. For example, if the hemoglobin concentration is to be determined, then a spectral selection means is centered, preferably at approximately 550 nanometers (nm). As another example, if the bilirubin concentration is to be determined, then a spectral selection means is centered, preferably at about 450 nm. The image capture means 260 is coupled to the image correction and analysis means 280 in a conventional manner. The image correction and analysis means 280 can be a computer or other type of processing. The image correction and analysis means 280 can be configured to carry out the image correction steps by means of physical elements, programming elements or a combination of physical elements and programming elements. These image correction steps will be described in detail later herein.
In still a further embodiment, the light source 202 is configured as a plurality of LEDs each LED emits a different wavelength of light. For example, three LEDs can be used to provide a green, blue and red light source. The use of a light source 202 that is configured to emit a particular wavelength or wavelengths of light, such as by means of one or more LEDs, can eliminate the need for a separate spectral selection means. An individual image capture means 260 can be used to capture the image of each of the three LEDs. For example, a single color camera sensitive to multiple wavelengths (green, blue and red) can be used to capture the image of each of the three LEDs (green, blue and red). In a further embodiment of the present invention, a light source can be optically coupled to a light tube, a single optical fiber or a bundle or bundle of optical fibers (not shown). Various light tubes and optical fibers are well known in the art and are available from many commercial optics. For example, a first end of a light tube (i.e., the near or extreme end of entry) can receive light emitted from the source of light. The second end of the light tube (i.e. the distal or far end) can be placed in the entrance pupil of the imaging device, such as the obstacle or stop 221. In this modality, an occultation, such as concealment 205 is designed in such a way that its diameter is smaller than the outside diameter of the light tube, to thereby create a high contrast illumination pattern that is projected onto the plane of the object. Other implementations of fiber coupled light sources will be apparent to those of skill in the art, given the present disclosure.
b. Second Mode According to a second embodiment of the present invention, illumination of the tissue region that is displayed can be provided in a more efficient manner. For example, devices 200 shown in Figure 2 project a high contrast illumination pattern over the region of tissue that is visualized, to thereby provide a low rotational effect due to the birefringence of the near field tissue. Still, the apparatus 200 requires a substantial amount of energy from the light source 202. The high output intensity could be necessary, in order to achieve providing enough illumination to saturate the annular ring out of the FOV of the detector 260, which produces enough light in the limiting numerical aperture of the objective lens of the detector. A relatively greater amount of energy is required because approximately 50% of the aligned illumination beam, collected by the collimator lens 204 is completely blocked by the concealment 205. For example, assume that the illumination source 202 is a tungsten filament, which is an emitter is i-Lambertian. Lambertian emitters have a radiant output distribution that varies as the cosine of the angle from the surface normal. Therefore, the concealment of the light emitted in the axis of the collimating lens (condenser) greatly reduces the radiant energy that is incident in the plane of the object. The amount of attenuation is greater than the ratio of the area hidden to the total area of the illumination beam. The amount of illumination (transmission or
"T") that is lost to an occultation in relation to the non-hidden value, can be determined by evaluating the following equation:
_ a cos (?) ci? or T = sin (ß) - sin (a) in 'where:
a = tan "(r.:/f) ri = clear aperture radius of the lens r: = radius of concealment f = distance from the condenser to the concealment For example if the clear aperture of the collimator lens has a subtended string or Angular amplitude of 30 degrees from the source and hiding has an angular subtended string of 14.5 degrees from the source, then the ratio of the areas from the clear opening to the concealment diameter is 40%, while the fraction of intensity loss emitted is approximately 50%. For example, a device similar to that shown in Figure 2 was modeled (that is, including an occultation) the model device engages approximately 38% of the light emitted on the axis and 28% from the points offset from the axis to the plane of the object. According to a second embodiment of the present invention, substantially, all the illumination collected or collected by the condenser from a small source, can be redistributed in an annular pattern or ring of light in an intermediate image plane, to transform in this way the lighting in a high-contrast lighting pattern. This "non-hidden" ring of illumination is then de-amplified and formed in image on the plane of the object by objective lens. This embodiment of the present invention eliminates the need to obscure a portion of the aligned illumination. Thus, no lighting is wasted from the source, in addition, the change in image contrast due to the angular orientation of the test and the alignment relative to the surface is minimized. According to this modality, the redistribution of the intensity of the light source can be carried out by means of the use of a frusto-conical mirror, a conical grid (a fixed, glowing, diffraction perimeter hole) or a hologram generated by computer. Figure 4 shows a block diagram of this embodiment (also referred to herein as the "frusto-conical mirror modality") of an image forming apparatus 400. The image forming apparatus 400 comprises a lighting system and an image formation system. The lighting system includes a light source 400, a conical lens, here shown as a frusto-conical mirror 405, and a field lens or relay 408. The image forming system includes an image capture means 460 and a target 417. Light source 402 illuminates a tissue region of a subject (shown in general, such as region 423). Similar to the light source 202 (described above with respect to Figure 2), the light source 402 may include, for example, a pulse-modulated xenon light arc or lamp, a mercury light arc or lamp, a halogen light or lamp, a tungsten light or lamp, a laser beam, a laser diode, or a light-emitting diode (LED). A collimator lens or capacitor 404 collects and collimates the illumination beam that leaves the light source 402 in a manner similar to that described above for the collimator lens 202 in FIG. 2. The illumination beam is propagated to a region of tissue 423 along a lighting path 406. Instead of blocking a portion of the illumination beam with a concealment, the apparatus 400 uses an optical element referred to as an "axicon" or truncated cone to generate a high contrast illumination pattern. it is projected onto the tissue region 423. A frusto-conical mirror is a cone-shaped optical element (also referred to as a conical lens) with a fixed apex angle that is symmetrical at approximately 360 degrees. This unique shape allows the frusto-conical mirror 405 to produce an annular pattern (or ring of light) in the distant field, such as the region of tissue 423. Figure 5A shows a detailed view of the frusto-conical mirror 405. A beam collimated light 502 is incident on surface 504 (here, the entrance surface). The propagation direction of the beam 502 is normal to the output surface 508. The beam is refracted around the conical axis 506 of the frusto-conical mirror. Unlike a typical curved lens, the input surface of the frusto-conical mirror 504 reaches a point at a vertex 507. This pointed apex causes the output beam, shown here as beams 510 and 512, arise at a constant angle. The angle by which the beam emerges from the frusto-conical mirror 405 is provided at a corner angle 509 and can be determined in accordance with Snell's law. In addition, only a minimum portion (approximately 1% or less) of the transmitted beam propagates parallel to the conical axis 506. An annular pattern or ring of light is formed in the 408 relay lens by the combination of the frusto-conical mirror 405 and a lens collimator, such as capacitor 404. The position of the collimating lens is preferably located such that the incident light in it is focused at infinity. Therefore, light from a point on the shaft, in general, arises from the collimator lens in parallel and propagates to infinity with little or no change in beam diameter. This light can be incident on the frusto-conical mirror 405 and then focused with an additional lens. In a preferred embodiment, the capacitor 404 is focused on the relay lens 408 and the frusto-conical mirror 405 is inserted in front of it. The focused image is then in the form of a ring of light on the relay lens. This ring of light can then be re-formed by the objective lens, such as objective 417, as the plane of the object, where it forms a smaller ring of light with a dark central region.
In a preferred embodiment, the outer diameter of the frusto-conical mirror 405 is large enough to receive the complete collimated beam of illumination. A frusto-conical mirror, such as the frusto-conical mirror 405 can be a molded element of plastic or glass molding. Trunk-conical mirrors are reliable to manufacture and simple enough to line up. Trunk-cone mirrors are available from several commercial lens vendors, such as Optics for Research, of New Jersey. Note that the selection of the entrance and exit surfaces is for description purposes only, a light beam can be incident on any surface 504 or surface 508 and be refracted in a similar manner. Alternatively, in accordance with this embodiment of the present invention, a conical grid or a computer generated hologram (ie, a holographic conical grid) can be used in place of the frusto-conical mirror 405 to achieve the same lighting pattern desired in the tissue region. A conical grid is a divergent, bright grid of fixed period. Conical grids are known in the art. The conical grids can be used as alignment accessories and to generate a diffraction-free propagation beam. For example, a front view of a conical grid 555 is shown in FIG. 5B. Preferably, the conical grid 555 has ring of equal spacing, shown by the spacing distance d, to thereby form a "bull's eye" pattern on the front surface of the conical grid 555. A side view corresponding to the conical grid 555 is shown in Figure 5C, which shows the conical grid, which has a birefringent surface profile. Since a beam of light is normally incident on the grid, the beam of light is diffracted at a constant exit angle. The transmitted beam output angle is proportional to the wavelength of the incident light, the spacing distance d and the angle of incidence of the light beam. After the encounter with a conical grid, only a minimum portion of the incident beam is transmitted parallel to its optical axis. A conical grid, with a spacing pattern specified by the user, can be made from glass or plastic elements according to the known photoprotective or injection molding method. For example, grids can be formed in photoprotective layer from interference patterns recorded in the combination of two or more laser beams. The diffraction characteristics are then coated with a metal, such as nickel for use in molding. Alternatively, a main metal can be precision machined using known diamond lathe technology. These main metals can then be used as mold surfaces for the injection or compression molding of plastics. In addition, an optical element that has a hologram (also referred to as a conical, holographic grid) can also be used to achieve a similar effect. The hologram is a product based on emulsion film that is coated on a glass substrate (or other suitable material). Methods of forming a hologram are known in the art. For example, holographic conical grids are generally produced by recording interference patterns generated by the combination of two or more laser beams, where these patterns are registered as main grids. The production versions can be formed as main grids or copied from main holograms. When used in the lighting system of the present invention, the combination of a conical grid and a field lens or a holographic conical grid and a field lens projects an annular pattern in the far field. With respect to the present invention, a conical grid or holographic element may be placed in the illumination path such as the illumination path 406 of FIG. 4. For example, the 555 conical grid can be placed in the lighting path, such as the top of a Kohler lighting system. An appropriately designed conical grid placed in a similar location to that of the frusto-conical mirror 405 diffracts the illuminated beam of illumination in a manner similar to that shown in Figure 4. The optical and physical parameters of the conical grid 555 or a holographic element , will be apparent to those skilled in the art based on the present disclosure. Returning to Figure 4, the projection or field lens 408 is used to collect and project the annular pattern formed in image onto the tissue region 423, in a capillary 424. The field lens 408 can be placed along the length of the illumination path 406 in an intermediate image plane 407. When a lamp having a filament as the light source 402 is used the placement of field lens 408 in the intermediate image plane 407 can prevent vignetting and loss resulting from light for points offset from the axis in the filament of the lamp, by bending the rays displaced from the axis towards the optical axis, such that they pass within the clear aperture of objective 417. Figure 6 represents an annular image pattern on the surface of a field lens, such as field lens 408. As a representative example, the lighting system comprises a light source, a collimator lens and a frusto-conical mirror. The truncated-conical mirror has a diameter of 6 millimeters (mm) with a collapse in the surface of approximately 0.75 mm and an apex angle of approximately 13 degrees. The field lens has a diameter of approximately 10 mm. This results in an annular pattern that is incident in the plane of the object having a diameter of approximately 1.8 mm. Preferably, the focal length of the field lens 408 is selected to form the image of the exit pupil of the frusto-conical mirror over the aperture stop (not shown) of the objective 417. This configuration couples most or all of the light collected by the capacitor 404 on the plane of the object 419. The image forming system of the apparatus 400 operates in a manner similar to that described above with reference to figure 2. In general, if the exit face of the frusto-conical mirror 405 and an inlet pupil 416 of objective 417 are of the same size, and the filament is quite small (e.g. about 1 mm in length), apparatus 400 can provide as much as 2.5 times more light to tissue region 423 than the apparatus 200. It is important to note that if a lamp is used as the light source 402, there is a greater opportunity for the collimated light beam to enter the frusto-conical mirror 405 at an angle. The resulting illumination beam will be offset from the axis with respect to. optical axis 406. In turn, the intensity transmitted through the frusto-conical mirror 405 and reaches the plane of the object can be reduced by as much as 50%. This illumination "displaced from the axis" is an exchange to consider when using a lamp as the light source which will lead to the ring illumination pattern being slightly off center (or slightly truncated). Thus, care must be taken when colliding the light source 402. Alternatively, if a laser or LED is used as the light source 402, the alignment is more direct since the emitted light emanates from a substantially individual point ( a point source). In a preferred embodiment, a concealment 409 may also be used to minimize any beam of illumination on the axis transmitted through the frusto-conical mirror 405 from the range tissue region 423 that is within the FOV of the image capture means 460 According to this embodiment, concealment 409 is placed in the illumination path between field lens 408 and tissue region 423. Since the intensity pattern in the relay lens is in the form of a ring with a dark center, an occultation can be placed in the center of the relay lens without blocking the desired lighting pattern, thus, only aberrant and deflected light will be blocked. For example, as shown in Figure 4, the concealment 409 is placed just after the field lens 408. The outer diameter of the concealment 409 is smaller than the inner diameter of the annular illumination pattern. Preferably, the concealment diameter 409 may be the same size as the FOV of the image capture means 460. In this manner, the entire annular pattern will reach the region of tissue 420 outside the FOV of the detector 406. Any light transmitted to Through the vertex of the vertex of the frusto-conical mirror 405 along the optical axis 406 will be blocked by the concealment 409, thereby improving the image contrast visualized by the detector 460. Other block means of any illumination on the axis will be apparent to those skilled in the art, given the present disclosure. Fig. 7 illustrates a ray pattern trace of the illumination and image beams for an experimental device 700. Similar to the device 400 shown in the figure, the device 700 comprises a light source 702, a capacitor 704, a truncated mirror conical 705 and a field lens 708, a beam splitter 718, a lens 717 and an image capture means 760. The illumination emanating or leaving the light source 702 is collimated by the capacitor 702 and then polarized by a polarizer 710. The frustoconical mirror 705 diffracts the illumination beam in a manner similar to that described above with reference to FIG. 4 for the frusto-conical mirror 405. In this example, the frusto-conical mirror 405 has a conical constant of approximately -19.0. The diffracted illumination beam, represented by the light rays 706, is aligned by the field lens 708. The illumination beam is redirected out of the beam splitter 718 through the objective 717 on a plane of the object (not shown), which is located just below the surface of film 724. The illumination beam has the general appearance of a light ring, similar to the pattern shown in figure 6. The combination of the field lens 708 and the objective 717 also act to focusing the annular illumination ring, however, according to the present invention, the illumination beam can be focused on an exit window 724, which corresponds to the film surface, outside the track field of the image capture means 760. For a preferred embodiment of the present invention, a sheet of optical formula (or optical prescription) corresponding to the ray trace and the device of figure 7, is listed below in the T abla 1. Note that the optical characteristics of each surface found by the illumination beam are listed below? Table 1
Table 1
The first column lists the number of surfaces that interact with the light that leaves source 702. Columns 2-5 list the optical and physical characteristics of each element. In practice, the control of spacings and curvatures is important to obtain a good performance. The tolerances in the spacings may vary, but preferably they are controlled to be within 0.1 mm. The numerical openings of the items listed are also important. For example, the numerical aperture size of any given element controls how much light is obtained through the image formation system. This can be taken into account by the clear aperture (diameter of the lens that is used to transmit light) of the lens elements. In addition, the focal length of each element is also important. The focal length of a given lens element is a function of the radius of curvature of each surface and the refractive index of the material used to make each element. In this example, objective 717 comprises two achromatic double lenses, with each double lens having two lenses attached to a common surface. However, a single lens lens can also be used to achieve similar results as will be apparent to one skilled in the art, given the present disclosure. The objective 717 focuses the illumination beam on the window 724, precisely outside the field of view of the image capture means 760. The image beam is propagated from a blood vessel (capillary vessel or tissue sample) 725, through the target 717, through beam splitter 718, towards image capture means 760, along an image path 707. Note that the illumination beam is incident on the film surface outside the FOV of the capture medium of image 760.
The coupling efficiency of the illumination intensity of this example is about 98% on the axis and 95% off the axis. In accordance with this embodiment of the present invention, this higher coupling efficiency allows the use of a lower power bulb for the light source 702. Furthermore, this embodiment of the present invention also has the advantages of reduced heat dissipation, required and lower power consumption for the light source 702. For example, using a 5 Watt lamp as the light source 702, the device 700 generates a virtual source of illumination within the tissue region, which has intensity of approximately 0.6. milliwatts (mW) (over the area of the illumination ring) that reaches the blood vessel or capillary vessel that is imaged with the image capture means 760. An additional advantage of this mode is that increased illumination can be used to achieve a higher signal-to-noise ratio for the image capture means 760. This increased signal-to-noise ratio provides results of an more accurate and stable lysis. If a CCD camera is used as the image capture means 760, this increased signal-to-noise ratio allows the application of the self-obturation for the exposure control. Self-sealing requires that the CCD camera is receiving enough illumination to saturate the detector even for the darkest conditions of use. If the illumination level is quite high, the self-sealing function can decrease the shutter exposure time to prevent saturation and achieve an optimal exposure level. In general, the modality of the frusto-conical mirror can provide more illumination in the plane of the object for a radiating output of given light source, while eliminating the angular orientation variations caused by the birefringence of the tissue in the background intensity and the contrast. The modality of the truncated-conical mirror, as well as the concealment modality, each reduces the contrast effects that reduce brightening in the captured image. The modality of the truncated-conical mirror allows reduced power consumption of the lamp, higher levels of illumination in the plane of the camera detector, reduced heat dissipation and the potential use of smaller lamps. Having higher illumination levels in the detector plane provides higher signal-to-noise ratios in a CCD camera or other detector, which allows more accurate determination of measurable image characteristics such as image intensity distributions and feature profiles. below the surface such as the width and density of blood veins and glands.
c. Third, Modality According to a third embodiment of the present invention, an image forming system comprises an improved folding mirror or beam splitter. Recall that Figure 2, a folding mirror or beam splitter 218 is used to redistribute light from the illumination system to the blood vessel as well as to the capillary vessel to the tissue sample that is imaged in the plane of the object. According to this modality, rather than using an occultation or conical lens in combination with a beam splitter of 50% reflection / 50% transmission, normal, an improved folding mirror can transform the illumination beam and project a lighting pattern high contrast on the plane of the object. The improved folding mirror or beam splitter can be designed as a mirror having a fully transmitting center (i.e. having 100% wavelength transmission of the illumination and / or image beam). With this method, a high-contrast illumination pattern is formed in the image on the plane of the object and almost 100% of the intensity of the image beam that reaches the folding mirror will be captured by the image capture means. The application of the improved folding mirror in this type of image forming system eliminates the need for a separate concealment or other means of redistribution of the light source. In addition, this type of configuration provides complete isolation between the light source and the image signal; as such, this modality has a much improved signal-to-noise ratio. Furthermore, in a preferred embodiment, the improved folding mirror can also be incorporated in the concealment mode in the concealment mode device and / or the frusto-conical mirror mode device discussed above. Thus, the intensity of the incident light beam in the region of the tissue and the intensity of the image beam reaching the image capture means can both be increased in a direct manner, thereby increasing the overall requirement in the device. in vivo image training. Figure 8A shows an arrangement of the block diagram of the in vivo imaging device 800. The device 800 uses an annular mirror as a folding mirror to provide a high contrast illumination pattern. The device 800 comprises an illumination system 803 and an image capture means or detector 860 that shares a common axis 807 through a single objective 817. A lighting axis 806 and the image axis 807 are combined along the axis 807 using a folding mirror 818 as shown in figure 8B as a 100% reflection mirror with an elliptical hole in its central region. Thus, a high contrast illumination pattern is reflected displaced from the folding mirror 818 and propagates along the path 807, which passes through the objective 817 before reaching a region of the fabric 824. In a preferred embodiment, the In vivo imaging device 800 comprises a lighting system 803, an image forming lens 817 and a detector 860. The lighting system 803 comprises a light source 802 and a collimating lens 804, together with the folding mirror 818 and objective 817. As shown in detail in Figure 8B, the folding mirror 818 is an annular mirror having a reflective surface of almost 100% (depending on the coating) around an elliptical ring 817 and a clear opening or central region 820 which is 100% transparent to the image beam and the illumination beam. The specific dimensions of the elliptic annulus and the central regions will depend on the angle of the folding mirror with respect to the image and illumination trajectories. In a preferred embodiment, the angle of the folding mirror 818 with respect to the illumination path 806 and the image path 807 is about 45 °. For example, Figure 8C shows exemplary dimensions for the folding mirror 818 based on a 45 degree inclination. Other dimensions of the folding mirror and of the angles of incidence will be apparent to those skilled in the art given the present disclosure.
Alternatively, the folding mirror 818 can be a flatter glass or plastic optical element, having a first surface that is coated with a dichroic coating, having 100% transmission in the center region 820 and 100% reflection the annular outer portion 819. This implementation allows a nearly 100% reflection of the illumination beam to the plane of the object, while allowing almost 100% of image transmission to the detector plane (excluding the mirror and Fresnel losses). Dichroic coatings are well known in the art and can be provided by many commercial coating vendors. In yet another embodiment, the folding mirror 818 may be a transparent glass plate having a aluminized, etched surface corresponding to the annular outer portion 819. In addition, a second non-reflective surface (not shown) of the folding mirror 818 It can be coated with an antireflection coating to minimize the loss of image signal that reaches the detector. Another advantage of this foldable mirror implementation is that the folding mirror 818 does not have to be bias sensitive. Thus, the image forming device uses the entire potential image beam. Other modifications to the foldable mirror 818 will be apparent to those skilled in the art, given the present disclosure. To further improve the image quality, crossed polarizers can be used in the device 800, in a similar manner as described above for the other embodiments of the present invention. As mentioned above, in a preferred embodiment, the folding mirror or beam splitter can also be incorporated in the concealment mode and in the beam mode device discussed above. For example, the folding mirror 818 can be replaced by the beam splitter 818 (see figure 2), beam splitter 218 (see figure 2), beam splitter 418 (see figure 4) or beam splitter 718 (see figure 7). ). For example, the folding mirror 818 was replaced in a device similar to the device 200. The predicted lighting pattern produced by this device is shown in Figure 8D. The incident illumination in the plane of the object is similar to the lighting patterns described above, in which all the illumination is incident on the plane of the object outside the FOV of the image capture means. In Figure 8D, the lighting pattern 850 is annular, where the inner diameter is approximately 1.5 mm. Thus, the complete illumination pattern incident on the plane of the object is located outside the FOV of the image capture means, illustrated by the FOV 855. Furthermore, the use of the folding mirror 818 of any of the modalities described above may increase the efficiency of the image formation device, global. Assume that the normal beam splitter has 50% transmission and 50% reflection at the wavelength of interest. By replacing a normal beam splitter with the folding mirror 818, the intensity of the illumination beam available in the tissue region is increased by a factor as much as two. Furthermore, having 100% transmission of the image beam increases the intensity of the image signal that reaches the image capture medium by a factor of two. Thus, the overall efficiency of the image formation system, in terms of image intensity per illumination intensity for the same light source, is increased by a factor of approximately four. As stated above, the illumination technique of the present invention greatly improves the image quality by creating a virtual illumination source from within a subject or living patient. For example, Figure 9 shows an example image obtained as using a device based on the concealment mode of the present invention. This image was obtained in the mucosal tissue beneath the tongue of a human test subject. The capillaries are visible as they will illuminate in transmission. The visible globular structures are individual squamous cells.
d. SUMMARY An important feature of the present invention is the creation of a virtual source from within the region of tissue that when visualized by the image capture means eliminates the need to fix the image forming device in a particular position, with respect to the region of the tissue that is visualized. In other words, the device of the present invention is insensitive to angular rotations and other movements because the dispersion of the near-field birefringent tissue layers is substantially reduced. In addition, the lighting techniques discussed here allow a flexible approach in the design of the instrument. For example, the improved folding mirror discussed in the third embodiment can also be used in the concealment mode or the frusto-conical mirror mode. Different light sources can be used depending on the types of measurements that are going to be taken. Different optical elements such as condensers, relay lenses and lenses can be used, as will be apparent to one skilled in the art, given the present description.
7. Image Analysis As mentioned above, the correction and image analysis means are used to process the new signal received by the image capture means and generate an image, such as that shown in Figure 9. Various types of different Image analysis techniques can be implemented in accordance with the present invention. For example, a polychromatic correction can eliminate the effect of tissue pigmentation, through which light travels to illuminate the shaped portion of the vascular system image. The pigmentation of the tissue will affect some wavelengths of light in the same way, so that the pigmentation effect of the tissue is canceled through the use of a polychromatic correction. A velocity correction may be applied to extract moving cells from a stationary background. Speed correction can be used alone, or in conjunction with, a polychromatic correction. There are only certain wavelengths that are equally absorbed by both arterial blood and venous blood. A wavelength that is equally absorbed by both arterial blood and venous blood is called an isobestic point. Such an isobestic point for hemoglobin is located at about 546 nm. In a preferred embodiment,? I is selected so that it is located near the center of a hemoglobin absorption band and so is located near or at an isobestic point. Una?: Adequate is 550 nm. In this way, the concentration of hemoglobin can be determined from the reflected spectral image formation of a large vessel, without considering whether the large vessel is an artery carrying arterial blood or a vein carrying venous blood. For example, Figure 10 illustrates an example process used to convert an untreated image 1010 into a result 1040. By "raw image" the image is implied before the application of a correction function 1015. The correction function 1015 it is applied to the untreated image 1010 to produce a corrected image 1020. The correction fusion 1015 normalizes the untreated image 1010 with respect to the image background. In one embodiment, the correction function 1015 is implemented by means of a bichromatic correction. For a bichromatic correction, two wavelengths,? I and? 2, are selected. By subtracting the image? 2 from the image? I, all the parameters that affect both? I and? 2 are canceled in the same way, and thus are eliminated in the resulting image (?? -? 2). The resulting image (? X-? 2) incorporates the effect of only those parameters that affect? I and? 2 differently. In another embodiment, the correction function 1015 is implemented by means of a speed or speed correction. For a speed correction, the corrected image 1020 is formed by taking the difference between the new image 1010 at a time tO and at a time ti. For this purpose, means for pressing the light and / or sealing an image capture means such as a camera can be provided, so that two different images are obtained at the same time. A velocity correction allows a portion of movement of the new image 1010 that is drawn from a stationary portion of the new image 1010. In this manner, the corrected image 1020 is formed to contain either the moving portion or the stationary portion of the image. the new image 1010. A segmentation function 1025 is applied to the corrected image 1020 to form an analysis image 1030. The segmentation function 1025 segments or separates a scene of interest from the corrected image 1020 to form the analysis image 1030. An analysis function 1035 is applied to analyze the image 1030 to produce the result 140. The scene of interest segmented by the segmentation function 1025 may depend on the type of analysis performed by the analysis function 1035. In this way, the corrected image 1020 can contain many interesting scenes that are segmented differently by several segmentation functions. The additional detailed description of several specific methods for performing the image analysis is provided in the '363 application mentioned above. The method illustrated in Figure 10 can be used to carry out non-invasive in vivo analysis of blood parameters for the purpose of diagnosis or monitoring. A means of image correction and analysis as exemplary as for use in the present invention, such as the image correction and analysis means 280 described above in Figure 2, is shown as a computer system 1100 in Figure 11. The computer system 1100 includes one or more processors, such as processor 1104. The processor 1104 is connected to a communication bus 1106. Several modes of programming elements are described in terms of this exemplary computer system. After reading this description, it will become apparent to a person skilled in the relevant art how to implement the invention using other computer systems and / or computer constructions. The computer system 1100 also includes a main memory 1108, preferably random access memory (RAM) and may also include a secondary memory 1110. The secondary memory 1110 may include, for example, a hard disk drive 1112 and / or a removable storage unit 1114, which represents a flexible disk unit, a magnetic tape unit, an optical disk unit, etc. The removable storage unit 1114 reads from and / or writes to a removable storage unit 1118 in a well-known manner. The removable storage unit 1118 represents a flexible disk, magnetic tape, optical disk, etc., which is read by and written to, the removable storage unit 1114. As will be appreciated, the removable storage unit 1118 includes a storage medium usable by computer, which has stored in it the programming elements and / or computer data. In alternative embodiments, the secondary memory 1110 may include another similar means for allowing computer programs or other instructions to be loaded into the computer system 1100. Such means may include, for example, a removable storage unit 1122 and an interface 1120 Examples of these may include a program cartridge and the cartridge interface
(such as that found in video game devices), a removable memory microcircuit (such as an EPROM or PROM) and the associated receptacle and other removable storage units 1122 and interface 1120 that allow the programming elements and data to be transferred from the removable storage unit 1122 to the computer system 1100. The computer system 1100 may also include a communication interface 1124. The communication interface 1124 allows the programming elements and data to be transferred to the computer system 1100 and external devices, such as the image capture means 260. Examples of communication interface 1124 may include a modem, a network interface (such as an internet card), a communications port, a PCMCIA slot and card, etc. . The programming elements and the data transferred via the communication interface 1124 are in the form of signals which can be electronic, electromagnetic1, optical or other signals capable of being received by the communication interface 1124. For example, an image signal is provided to the communication interface via a channel 1128. Channel 1128 carries the signal and can be implemented using wire or cable, optical fiber, a telephone line, a cellular telephone link, an RF link and other communication channels. In this description, the terms "computer program medium" and "computer usable medium" are generally used to refer to media such as the removable storage device 1118, a hard disk installed in the hard disk drive llll and signals provided via channel 1128. These computer program products are means for providing programming elements to computer system 1100. Computer programs (also called computer control logic) are stored in main memory 1108 and / or secondary memory 1110. Computer programs may also be received via communications interface 1124. Such computer programs, when executed, allow the computer system 1100 to perform the features of the present invention as discussed herein. In particular, computer programs when executed allow the processor 1104 to perform the image analysis features of the present invention. Accordingly, such computer programs represent controllers of the computer system 1100. In one embodiment, where the invention is implemented using programming elements, the programming elements can be stored in a computer program product and loaded into the computer system. 1100 using the removable storage unit 1114, the hard disk drive 1112 or the communication interface 1124. The control logic (programming elements), when executed by the processor 1104, causes the processor 1104 to perform the analysis functions of the invention as described herein. In another embodiment, the invention is mainly implemented in computer accessories using, for example, computer accessory components such as the application of specific integrated circuits (ASIC). The implementation of the machine established with the computer accessories to perform the functions described herein, will be apparent to those skilled in the relevant art. In yet another embodiment, the invention is implemented using a combination of both computer accessories and programming elements.
8. Applications In summary, the device and method of the present invention can also be used to determine various characteristics of a vascular system in a non-invasive manner. In a practical application of the present invention, the modalities described in detail below, can be implemented in a compact device or probe. The following description is not intended to limit the applications of the present invention. It is provided as an exemplary use of the present invention. Other alterations or modifications will be apparent to those skilled in the art based on the present invention. Figures 12A and 12B show embodiments of the present invention suitable for use with a subject to perform non-invasive in vivo analysis. Figure 12A shows a console unit 1202 containing a probe 1204, a printer 1206 and a processing and storage unit 1208. Probe 1204 is used to image the portion of the subject's vascular system, such as the inside of the lip lower. An indicator coupling medium, such as ethyl cellulose or a sugar syrup, is preferably applied to the probe 1204 to provide good optical contact or optical seal between the probe 1204 and the interior of the lower lip. Probe 1204 is preferably equipped with the elements shown in Figures 2, 4, 7 and / or 8A (or any combination thereof). For example, with respect to Figure 2, the probe 1204 is equipped with a light source 202 through one or more image capture means. To ensure optimum effectiveness of the apparatus of the present invention, there should be nothing in the light path between the polarizer 210 and the polarizer 220 that depolarizes the light. For example, the presence of dust in the light path between polarizer 1510 and polarizer 1520 will degrade the effectiveness of the apparatus. In addition, the components of the probe 1204 are preferably made of non-depolarizing material so that the materials will not depolarize the light. A particularly preferred material for the components of probe 1204 in the light path is a non-depolarizing non-birefringent plastic material available from Kodak under the tradename KODACEL. Other suitable materials for the components in the light path are glass or quartz. In addition, the interior of the probe 1204 can be coated with an anti-scatter coating such as Martin Black or Orlando Black, which are available from commercial coatings vendors. These anti-dispersion coatings can be used to further reduce the internal dispersion of probe 1204. A preferred material for the imaging end of probe 1204 is glass. The image signal is transmitted from the probe 1204 to the processing and storage unit 1208 for processing and storage. Fig. 12B shows a mobile unit 1222. Mobile unit 1222 includes a probe 1224 and a band unit 1226. Probe 1224 can be configured in a manner similar to probe 1204 shown in Fig. 12A. The band unit 1226 includes a data storage and transmission unit 1228. The data storage and transmission unit 1228 receives the signals from the probe 1224. These signals can be stored by the data storage and transmission unit 1228 for the processing at a later time. Alternatively, these signals can be transmitted by the data storage and transmission unit 1228 to a central processing station (not shown) for processing and storage. The central processing station can be configured to provide permanent storage for the processed data as well as to print and display the results in a well-known manner. The band unit 1226 also includes a location 1229 for batteries or other appropriate power source. The in vivo apparatus of the present invention can be used to carry out the method of the present invention discussed above. In particular, the in vivo apparatus can be used to determine hemoglobin and bilirubin concentrations per unit volume of blood. The in vivo apparatus can also be used to determine the hematocrit and the mean cell volume. The in vivo device can also be used to determine the number of white blood cells and the number of platelets per unit volume of blood. To determine the number of cells such as • white blood cells or platelets, the light source is configured as a pulsed light source or light signal to "stop the action" in the analysis image so that the counting can be done. The stopping action achieved with the pulsed light source avoids the blur associated with the movement of the analysis image. The pulsed light source is synchronized, preferably, with the frame rate of the image capture means. The detection action can also be achieved by controlling the closure in the image capture medium. A stop action image is preferred at the time that a cell count is to be made in the analysis image. A stop action image may also be used to determine other parameters that are not cell counts, such as Hb or Hct. However, other parameters such as Hb and Hct can also be determined with an action image without stopping. Other types of image analysis consistent with the examples discussed above will be apparent to those skilled in the art based on the present disclosure. By using the device and method of the present invention to provide a spectral image of large vessels, the parameters of hemoglobin (Hb), hematocrit (Hct) and white blood cell count (WBC) can be determined directly. By using the device and method of the present invention to provide a spectral image of small vessels, the average cell volume (MCV), the average cell hemoglobin concentration (MCHC) and platelet count (Plt) can be determined directly. ).
9. Conclusion While 'that several modalities of the present! invention have been described above, it should be understood that these have been presented by way of example only and not limitation. The illumination techniques of the present invention can be used in any analytical application, i in vivo or in vitrb which optically requires the measurement or I I visually the measurement of the characteristics of an object.
Thus, the scope and scope of the present invention should not be limited by any of the exemplary embodiments! described above, but should be defined only in accordance with the following claims and their equivalents. It is noted that, in relation to this date, the best method known to the applicant to carry out said invention is that which is clear from the present description of the invention.
Claims (24)
- CLAIMS Having described the invention as above, it is claimed as property, contained in the following claims: 1. An apparatus for detecting the optical characteristics of a sub-surface object located in a plane of the object, which has a light source to provide a beam of illumination that propagates along a path of illumination defined by the light source and the object, characterized in that it comprises: a lighting system that transforms the beam of illumination into a configuration or pattern of high contrast illumination and projects such a configuration or pattern of illumination on the sub-surface object substantially outside of a desired portion of the sub-surface object to be imaged and an image formation system that includes an image capture device for detecting an image of the desired portion of the sub-surface object, the image is formed by scattered illumination With the high contrast illumination pattern that is transmitted through the sub-surface object and propagates along an image path to the image capture device, the image path is defined by the object and the capture means of image.
- 2. The apparatus in accordance with the claim 1, characterized in that the high contrast illumination pattern has a high intensity region and a low intensity region and wherein the illumination system projects the high intensity region out of a field of view of the image capture means in the plane of the object.
- 3. The apparatus in accordance with the claim 2, characterized in that it further comprises: a condenser arranged between the light source and the plane of the object to collimate the illumination beam, the collimated illumination beam is propagated to the illumination system.
- The apparatus according to claim 2, characterized in that the lighting system comprises: a folding or folding mirror disposed between the light source and the plane of the object, the folding mirror includes a surface having a substantial external portion reflective body and a substantially transmitting internal portion, wherein the folding mirror transforms the illumination beam to the high contrast illumination pattern and directs the high contrast illumination pattern onto the plane of the object and wherein the image is substantially transmitted through the inner portion along the image path to the image capture device.
- The apparatus according to claim 2, characterized in that it further comprises: a target placed between the object plane and the image capture device along the image path, the objective also directs the high light pattern contrast on the plane of the object and the objective amplifies the image on the image capture device.
- The apparatus according to claim 5, characterized in that the illumination system comprises: a generator of the illumination pattern, placed between the light source and the plane of the object to transform the illumination beam into the high illumination pattern contrast; a projection lens placed between the generator of the illumination pattern and the plane of the object projecting the high-contrast illumination pattern onto the plane of the object; and a folding mirror, placed between the optical element and the plane of the object and placed between the plane of the object and the image capture device, to direct the high contrast illumination pattern, projected along the image path over the plane of the object.
- 7. The apparatus in accordance with the claim 6, characterized in that the illumination pattern generator comprises a concealment placed between the light source and the optical element, the concealment blocks a first portion of the illumination beam corresponding to the low intensity region of the high contrast illumination pattern and in where a second portion of the illumination beam corresponds to the high intensity portion of the high contrast illumination pattern.
- 8. The apparatus in accordance with the claim 7, characterized in that the concealment is placed along the illumination path in a first aperture, wherein an exterior diameter of the concealment corresponds to the field of view of the image capture device and wherein the projection lens and the objective forms the image of the concealment on the plane of the object.
- The apparatus according to claim 6, characterized in that the generator of the illumination pattern comprises: a conical lens positioned between the light source and the projection lens, the conical lens redistributes the illumination beam in an annular pattern, the annular pattern projected on the piano of the object through the projection lens, where the annular pattern has a central region of low intensity.
- 10. The apparatus according to claim 9, characterized in that the conical lens is a frusto-conical mirror.
- The apparatus according to claim 6, characterized in that the illumination pattern generator comprises: a conical grid positioned between the light source and the projection lens, the conical grid redistributes the illumination beam in an annular pattern, the annular pattern projected on the object of the plane by means of the projection lens where the annular pattern has a central region of low intensity.
- The apparatus according to claim 6, wherein the illumination pattern generator comprises: an optical element positioned between the light source and the projection lens, the optical element has a hologram coated with a surface of the optical element for redistributing the illumination beam in an annular pattern, the annular pattern projected onto the plane of the object by the projection lens, wherein the annular pattern has a central region of low intensity.
- The apparatus according to claim 6, characterized in that it further comprises: a first polarizer positioned between the light source and the foldable mirror to polarize the illumination beam from the light source; and a second polarizer positioned along the image path between the collapsible mirror and the image capture device, wherein a polarization plane of the second polarizer is substantially orthogonal to a polarization plane of the first polarizer.
- The apparatus according to claim 1, characterized in that the sub-surface object comprises a predetermined region of tissue and blood vessels located below the surface of a subject's skin, to allow in vivo, non-invasive analysis of a tissue and blood of the subject, the lighting system comprises: means for transforming the light that exits or emanates from the light source in a pattern of illumination having a region of low intensity and a region of high intensity, and means for projecting the low intensity region of the illumination pattern on the sub-surface object and for projecting the high intensity region of the illumination pattern on the sub-surface object substantially outside the region of interest; and the image capture means for capturing an image of the predetermined region, formed by scattered illumination of the high intensity illumination pattern that is transmitted through the object to the region of interest and propagated along an image path , formed between the object and the medium and the image capture means to the image capture device.
- 15. The apparatus in accordance with the claim 14, characterized in that the means for projection direct the high intensity region of the illumination pattern to a portion of the region of interest to the outside of a field of view of the image capture means.
- 16. The apparatus in accordance with the claim 15, characterized in that, when the illumination pattern reaches the surface, the light of the high intensity region of the illumination pattern interacts with matter within the region of interest -and is scattered by one or more scattering events, to form in this way a sub-surface lighting source to illuminate the object.
- 17. The apparatus in accordance with the claim 16, characterized in that the image is formed by a substantial portion of the sub-surface illumination source that is transmitted through the object along the image path.
- 18. A method for creating a light source in a region of sub-surface tissue containing an object of interest, wherein the object is illuminated from all directions around a plane of the object where the object is located, wherein an image of the object is detected by an image capture device, characterized in that it comprises the steps of: (a) providing a light source; (b) transforming the light from the light source to a lighting pattern having a high intensity portion and a low intensity portion; (c) directing the illumination pattern on a surface of the tissue region, such that the high intensity portion of the illumination pattern is incident in the plane of the object substantially only to the outside of a display field of the illumination capture device. image; and (d) detecting scattered light interacting with the object, with the image capture device, wherein the high intensity portion of the illumination pattern is subjected to one or more scattering events in the sub-surface tissue region .
- The method according to claim 18, characterized in that it further comprises the step of: (e) performing a transmission measurement of the sub-surface tissue region.
- The method according to claim 18, characterized in that step (b) further comprises: blocking a portion of the light from the source, the blocked portion corresponds to the low intensity portion of the illumination pattern.
- The method according to claim 18, characterized in that step (b) further comprises: providing a folding mirror having a first surface that includes a substantially reflective outer portion and an internal substantially transmitting portion, wherein the reflected light at the The outer portion of the substantially reflective outer portion corresponds to the high intensity portion of the illumination pattern.
- The method according to claim 18, characterized in that step (b) further comprises: providing an optical element for redistributing light in an annular pattern corresponding to the illumination pattern.
- 23. An apparatus for optically penetrating an object and detecting the optical characteristics of its sub-surface of an object according to claim 1, characterized in that: the light source illuminates the object at a wavelength such that the depth of dispersion Multiple is small compared to the penetration depth of the lighting light; the apparatus further comprises a first polarizer for polarizing the light from the light source; and a second polarizer placed in the image path between the object and the image forming medium through which the scattered light passes, wherein a polarization plane of the second polarizer is substantially orthogonal with respect to a plane of polarization of the first polarizing.
- 24. An apparatus according to claim 1, for quantitatively measuring the absorption properties of an object formed in image, characterized in that it further comprises: a light source for illuminating an object to be imaged; a first polarizer placed in the path of illumination between the light source and the object to polarize the light that emanates or exits from the light source; a second polarizer placed in an image path defined by the object and the image capture means, wherein a polarization plane of the second polarizer is substantially orthogonal with respect to a polarization plane of the first polarizer; and measuring means coupled to the image capture means for quantitatively measuring the differences in absorption properties between the structures formed in image, using the image.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US60/107,203 | 1999-09-22 | ||
| US09401859 | 1999-09-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA01004555A true MXPA01004555A (en) | 2002-07-25 |
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