US20020007123A1 - Method and system for characterization and mapping of tissue lesions - Google Patents
Method and system for characterization and mapping of tissue lesions Download PDFInfo
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- US20020007123A1 US20020007123A1 US09/739,089 US73908900A US2002007123A1 US 20020007123 A1 US20020007123 A1 US 20020007123A1 US 73908900 A US73908900 A US 73908900A US 2002007123 A1 US2002007123 A1 US 2002007123A1
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Definitions
- the present invention is directed to a method and apparatus for the in vivo, non invasive detection and mapping of the biochemical and/or functional pathologic alterations of human tissues.
- Cancer precursors signs are the so called pre-cancerous states, which are curable if they are detected at an early stage.
- the lesion can progress in depth, resulting in the development of invasive cancer and metastases.
- the possibilities of successful therapy are dramatically diminished. Consequently, the early detection and the objective identification of the severity (stage) of the precancerous lesion are of crucial importance.
- biopsy samples are obtained from suspicious areas, which are submitted for histological examination.
- biopsy sampling poses several problems, such as : a) risk for sampling errors associated with the visual limitations in detecting and localizing suspicious areas; b) biopsy can alter the natural history of the intraepithelial lesion; c) mapping and monitoring of the lesion require multiple tissue sampling, which is subjected to several risks and limitations; d) the diagnostic procedure performed with biopsy sampling and histologic evaluation is qualitative, subjective, time consuming, costly and labor intensive.
- Dombrowski in U.S. Pat. No. 5,424,543 describes a multi-wavelength, imaging system, capable of capturing tissue images in several spectral bands. With the aid of such a system it is possible in general to map characteristics of diagnostic importance based on their particular spectral characteristics. However, due to the insignificance of the spectral differences between normal and pathologic tissue, which is in general the case, inspection in narrow spectral bands does not allow the highlighting of these characteristics and even more so, the identification and staging of the pathologic area.
- D. R. Sandison et al in U.S. Pat. No. 5,920,399 describe an imaging system, developed for the in vivo investigation of cells, which combines multi-band imaging and light excitation of the tissue.
- the system also employs a dual fiber optic bundle for the transferring of the emitted from the source light onto the tissue and the remitted light from the tissue to the optical detector. These bundles are placed in contact with the tissue, and various wavelengths of excitation and imaging are combined in attempt to enhance the spectral differentiation between normal and pathologic tissue.
- the conventional (non-spectral) imaging techniques provide the capability of mapping characteristics of diagnostic importance in two or three dimensions. They are basically used for measuring morphological characteristics and as clinical documentation tools.
- the optics used for the imaging of the area of interest are of general purpose and are not comply with the special technical requirements for the clinical implementation of the method.
- Clinical implementation of the presented system is also hindered by the fact that it does not integrate appropriate means for ensuring the stability of the relative position between the tissue surface and image capturing module, during the snapshot imaging procedure. This is very important since small movements of the patient (i.e. breathing) are always present during the examination procedure. If micro-movements are taking place during successive capturing of images, after application of the agent, then the spatial features of the captured images are not coincide. This reduces substantially the precision in the calculation of the curves in any spatial point, that express the kinetics of marker-tissue interaction.
- the present invention provides, at least in part, a method for monitoring the effects of a pathology differentiating agent on a tissue sample by applying a pathology differentiating agent, e.g., acetic acid, on a tissue sample and monitoring the rate of change of light reflection from the tissue sample over time, thereby monitoring the effects of a pathology differentiating agent on a tissue sample.
- a pathology differentiating agent e.g., acetic acid
- the tissue may be a cervical, ear, oral, skin, esophagus, or stomach tissue.
- the pathology differentiating agent provokes transient alterations in the light scattering properties of the tissue, e.g., the abnormal epithelium.
- the present invention features a method for the in vivo diagnosis of a tissue abnormality, e.g., a tissue atypia, a tissue dysplasia, a tissue neoplasia (such as a cervical intraepithelial neoplasia, CINI, CINII, CINIII) or cancer, in a subject.
- a tissue abnormality e.g., a tissue atypia, a tissue dysplasia, a tissue neoplasia (such as a cervical intraepithelial neoplasia, CINI, CINII, CINIII) or cancer
- the method includes contacting a tissue in a subject with a pathology differentiating agent, e.g., an acetic acid solution or a combination of solutions selected from a plurality of acidic and basic solutions, exposing the tissue in the subject to optical radiation; and monitoring the intensity of light emitted from the tissue over time, thereby diagnosing a tissue abnormality in a subject.
- a pathology differentiating agent e.g., an acetic acid solution or a combination of solutions selected from a plurality of acidic and basic solutions
- the optical radiation may be broad band optical radiation, preferably polarized optical radiation.
- the non-invasive methods of the present invention are useful for the in vivo early detection of tissue abnormalities/alterations and mapping of the grade of these tissue abnormalities/alterations, caused in the biochemical and/or in the functional characteristics of epithelial tissues, during the development of tissue atypias, dysplasias, neoplasias and cancers.
- the tissue area of interest is illuminated with a broad band optical radiation and contacted with a pathology differentiating agent, e.g., an agent or a combination of agents which interact with pathologic tissue areas characterized by an altered biochemical composition and/or cellular functionality and provoke a transient alteration in the characteristics of the light that is re-emitted from the tissue.
- a pathology differentiating agent e.g., an agent or a combination of agents which interact with pathologic tissue areas characterized by an altered biochemical composition and/or cellular functionality and provoke a transient alteration in the characteristics of the light that is re-emitted from the tissue.
- the light that is re-emitted from the tissue may be in the form of reflection, diffuse scattering, fluorescence or combinations or subcombinations thereof.
- the intensity of the light emitted from the tissue may be measured, e.g., simultaneously, in every spatial point of the tissue area of interest, at a given time point or over time (e.g., for the duration of agent-t
- a diagnosis may be made based on the quantitative assessment of the spatial distribution of alterations in the characteristics of the light re-emitted from the tissue at given time points, before and after the optical and chemical excitation of the tissue and/or based on the quantitative assessment of the spatial distribution of parameters, calculated from the characteristic curves that express the kinetics of the provoked alterations in the characteristics of the light re-emitted from the tissue, which characteristic curves are simultaneously measured in every spatial point of the area under examination during the optical and chemical excitation of the tissue.
- the step of tissue illumination comprises exposing the tissue area under analysis to optical radiation of narrower spectral width than the spectral width of the light emitted by the illumination source.
- the step of measuring the intensity of light comprises measuring the intensity of the re-emitted light in a spectral band, the spectral width of which is narrower than the spectral width of the detector's sensitivity.
- the step of measuring the intensity of light comprises measuring simultaneously the intensity of the re-emitted light in a plurality of spectral bands, the spectral widths of which are narrower than the spectral width of the detector's sensitivity.
- the present invention features an apparatus for the in vivo, non-invasive early detection of tissue abnormalities/alterations and mapping of the grade of these tissue abnormalities/alterations, caused in the biochemical and/or in the functional characteristics of epithelial tissues, during the development of tissue atypias, dysplasias, neoplasias and cancers.
- the apparatus includes optics for collecting the light re-emitted by the area under analysis, selecting magnification and focusing the image of the area; optical imaging detector(s); means for the modulation, transfer, display and capturing of the image of the tissue area of interest; a computer which includes data storage, processing and analysis means; a monitor for displaying images, curves and numerical data; optics for the optical multiplication of the image of the tissue area of interest; a light source for illuminating the area of interest; optionally, optical filters for selecting the spectral band of imaging and illumination; means for transmitting light and illuminating the area of interest; control electronics; and optionally, software for the analysis and processing of data, which also enables the tissue image capturing and storing in specific time points and for a plurality of time points, before and after administration of the pathology differentiating agent.
- an image or a series of images may be created which express the spatial distribution of the characteristics of the kinetics of the provoked changes in the tissue's optical characteristics, before and after the administration of the agent, with pixel values corresponding with the spatial distribution of the alterations in the intensity of the light emitted from the tissue, in given time instances, before and after the optical and chemical excitation of tissue and/or with the spatial distribution of parameters derived from the function: pixel gray value versus time.
- the foregoing function may be calculated from the captured and stored images and for each row of pixels with the same spatial coordinates.
- the step of optical filtering the imaging detector comprises an optical filter that is placed in the optical path of the rays that form the image of the tissue, for the recording of temporally successive images in a selected spectral band, the spectral width of which is narrower than the spectral width of the detector's sensitivity.
- the image multiplication optics comprise light beam splitting optics that create two identical images of the area of interest, which are recorded by two imaging detectors, in front of which optical filters are placed, with in general different transmission characteristics and capable of transmitting light of spectral width shorter than the spectral width of the detector's sensitivity, so that two groups of temporally successive images of the same tissue area are recorded simultaneously, each one corresponding to a different spectral band.
- the image multiplication optics comprise more than one beam splitter for the creation of multiple identical images of the area of interest, which are recorded by multiple imaging detectors, in front of which optical filters are placed, with, preferably, different transmission characteristics and capable of transmitting light of spectral width shorter than the spectral width of the detector's sensitivity, so that multiple groups of temporally successive images of the same tissue area are recorded simultaneously, each one corresponding to a different spectral band.
- the image multiplication optics comprise one beam splitter for the creation of multiple identical images of the area of interest, which are recorded by multiple imaging detectors, in front of which optical filters are placed with, preferably, different transmission characteristics and capable of transmitting light of spectral width shorter than the spectral width of the detector's sensitivity, so that multiple groups of temporally successive images of the same tissue area are recorded simultaneously, each one corresponding to a different spectral band.
- the image multiplication optics comprise one beam splitter for the creation of multiple identical images of the area of interest, which are recorded in different sub-areas of the same detector, and in front these areas optical filters are placed with, preferably, different transmission characteristics and capable of transmitting light of spectral width shorter than the spectral width of the detector's sensitivity, so that multiple groups of temporally successive images of the same tissue area are recorded simultaneously in the different areas of the detector, each one corresponding to a different spectral band.
- the step of filtering the light source comprises an optical filter, which is placed in the optical path of an illumination light beam, and transmits light of spectral width shorter than the spectral width of sensitivity of the detector used.
- the step of filtering the light source comprises a plurality of optical filters and a mechanism for selecting the filter that is interposed to the tissue illumination optical path, thus enabling the tuning of the center wavelength and the spectral width of the light illuminating the tissue.
- the mapping of the grade of the alterations to the biochemical and/or functional characteristics of the tissue area of interest is based on the pixel values of one image, from the group of the recorded temporally successive images of the tissue area of interest.
- the mapping of the grade of the alterations to the biochemical and/or functional characteristics of the tissue area of interest is based on the pixel values belonging to plurality of images, which are members of the group of the recorded temporally successive images of the tissue area of interest.
- the mapping of the grade of the alterations to the biochemical and/or functional characteristics of the tissue area of interest is based on numerical data derived from mathematical operations and calculations between the pixel values belonging a plurality of images, which are members of the group of the recorded temporally successive images of the tissue area of interest.
- a pseudo-color scale which represents with different colors the different pixel values of the image or of the images used for the mapping of abnormal tissue areas, is used for the visualization of the mapping of the grade of the alterations to the biochemical and /or functional characteristics of the tissue area under examination.
- the image or images which are determined for the mapping of the grade of the alterations in biochemical and/or functional characteristics of tissue are used for the in vivo detection, mapping, as well as for the determination of the borders of epithelial lesions.
- the pixel values of the image or of the images which are determined for the mapping of the grade of alterations in biochemical and/or functional characteristics of tissue are used as diagnostic indices for the in vivo identification and staging of epithelial lesions.
- the image or the images which are determined for the mapping of the grade of the alterations in biochemical and/or functional characteristics of tissue can be overimposed onto the color or black and white image of the same area of tissue under examination displayed on the monitor, so that abnormal tissue areas are highlighted and their borders are demarcated, facilitating the selection of a representative area for taking a biopsy sample, the selective surgical removal of the abnormal area and the evaluation of the accuracy in selecting and removing the appropriate section of the tissue.
- the image or the images which are determined for the mapping of the grade of alterations in biochemical and/or functional characteristics of tissue are used for the evaluation of the effectiveness of various therapeutic modalities such as radiotherapy, nuclear medicine treatments, pharmacological therapy, and chemotherapy.
- the optics for collecting the light re-emitted by the area under analysis comprises the optomechanical components employed in microscopes used in clinical diagnostic examinations, surgical microscopes, colposcopes and endoscopes.
- the apparatus may comprise a speculum, an articulated arm onto which the optical head is attached, which optical head comprises a refractive objective lens, focusing optics, a mechanism for selecting the magnification, an eyepiece, a mount for attaching a camera, and an illuminator, where the speculum is attached in a fixed location onto the system articulated arm-optical head, in such a way such that the central longitudinal axis of the speculum is perpendicular to the central area of the objective lens, so that when the speculum is inserted into the vagina and fixed in it, the relative position of the image-capturing optics and of the tissue area of interest remains unaltered, regardless of micro-movements of the cervix, which are taking place during the examination of the female subject.
- the apparatus may further comprise an atomizer for delivering the agent, where the atomizer is attached in a fixed point onto the system articulated arm-optical head of the apparatus and in front of the vaginal opening, where the spraying of the tissue may be controlled and synchronized with a temporally successive image capturing procedure, with the aid of electronic control means.
- the image capturing detector means and image display means comprise a camera system with detector spatial resolution greater than 1000 ⁇ 1000 pixels and a monitor of at least 17 inches (diagonal), so that high magnification is ensured together with a large field of view, while the image quality is maintained.
- microscopes used in clinical diagnostic examinations comprise an articulated arm onto which the optical head is attached, which optical head comprises an objective lens, focusing optics, a mechanism for selecting the magnification, an eyepiece, a mount for attaching a camera, an illuminator and two linear polarizers, where the two linear polarizers are attached, one at a point along the optical path of the illuminating light beam and the other at a point along the optical path of the rays that form the image of the tissue, with the capability of rotating the polarization planes of these light polarizing optical elements, so that when these planes are perpendicular to each other, the contribution of the tissue's surface reflection to the formed image is eliminated.
- the endoscope may comprise optical means for transferring light from the light source onto the tissue surface and for collecting and transferring along almost the same axis and focusing the rays that form the image of the tissue, and two linear polarizers, where the two linear polarizers are attached, one at a point along the optical path of the illuminating light beam and the other at a point along the optical path of the rays that form the image of the tissue, with the capability of rotating the polarization planes of these light polarizing optical elements, so that when these planes are perpendicular to each other, the contribution of the tissue's surface reflection to the formed by the endoscope image is eliminated.
- surgical microscopes and colposcopes may additionally comprise a reflective objective lens, where the reflective objective replaces the refractive one, which reflective objective is devised so that in the central part of its optical front aperture the second reflection mirror is located, and in the rear part (non-reflective) of this mirror, illumination means are attached from which light is emitted toward the object, so that with or without illumination beam zooming and focusing optics the central ray of the emitted light cone is coaxial, with the central ray of the light beam that enters the imaging lens, and with the aid of zooming and focusing optics of illumination beam that may be adjusted simultaneously and automatically with the mechanism for varying the magnification of the optical imaging system, the illuminated area and the field-of-view of the imaging system, are varying simultaneously and proportionally, so that any decrease in image brightness caused by increasing the magnification, is compensated with the simultaneous zooming and focusing of the illumination beam.
- the reflective objective replaces the refractive one, which reflective objective is devised so that in the central part of its optical
- FIG. 1 is a schematic representation of the present method's basic principle.
- FIG. 2 illustrates an embodiment of the invention comprising a method for capturing in two spectral bands simultaneously and in any spatial point of the area under analysis, the kinetics of the alterations in the characteristics of the remitted from the tissue light, before and the after the administration of the contrast enhancing agent
- FIG. 3 illustrates another embodiment of the invention comprising a method for capturing in different spectral bands simultaneously and in any spatial point of the area under analysis, the kinetics of the alterations in the characteristics of the remitted from the tissue light, before and the after the administration of the contrast enhancing agent.
- FIG. 4 illustrates a schematic diagram of a medical microscope comprising a light source (LS), a magnification selection mechanism (MS), an eyepiece (EP) and a mount for attaching the image capturing module (CA), (detector(s), readout electronics etc).
- LS light source
- MS magnification selection mechanism
- EP eyepiece
- CA image capturing module
- CA image capturing module
- FIG. 5 illustrates an endoscope comprising an eyepiece (EP), which can be adapted to an electronic imaging system, optical fibers or crystals for the transmission of both illumination and image rays, optics for the linear polarization of light, one interposed to the optical path of the illumination rays (LE) and one to the path of the ray that form the optical image of the tissue (II).
- EP eyepiece
- optical fibers or crystals for the transmission of both illumination and image rays
- optics for the linear polarization of light one interposed to the optical path of the illumination rays (LE) and one to the path of the ray that form the optical image of the tissue (II).
- FIG. 6 depicts a colposcopic apparatus comprising an articulated arm (AA), onto which the optical head (OH) is affixed, which includes a light source (LS), an objective lens (OBJ), an eye-piece (EP) and optics for selecting the magnification (MS).
- AA articulated arm
- OH optical head
- LS light source
- OBJ objective lens
- EP eye-piece
- MS magnification
- FIG. 7 illustrates an optical imaging apparatus which comprises a light source located at the central part of its front-aperture.
- the present invention is directed to a method and system for the in-vivo, non-invasive detection and mapping of the biochemical and or functional alterations of tissue, e.g., tissue within a subject.
- tissue e.g., tissue within a subject.
- this agent is administered, e.g., topically to the tissue.
- the tissue (T) is sprayed using an atomizer (A), which contains the agent, e.g., acetic acid.
- the tissue is illuminated with a source that emits light at a specific spectral band, depending on the optical characteristics of both the agent and the tissue.
- Illumination and selection of the spectral characteristics of the incident to the tissue light can be performed with the aid of a light source (LS) and a mechanism for selecting optical filters (OFS).
- LS light source
- OFS optical filters
- images can be captured and used as reference.
- the detector (D) captures images of the tissue, in successive time instances, which are then stored in the computer's data-storage means.
- the capturing rate is proportional to the rate at which the tissue's optical characteristics are altered, following the administration of the agent.
- FIG. 1 images of the same tissue area are schematically illustrated, which have been stored successively before and after administering the agent (STI).
- the black areas represent tissue areas that do not alter their optical characteristics (NAT), while the gray-white tones represent areas which alter their optical characteristics (AT), following the administration of the agent.
- NAT tissue areas that do not alter their optical characteristics
- AT optical characteristics
- FIG. 1 two curves are illustrated: pixel value in position xy (Pvxy), versus time t.
- the curve ATC corresponds to an area where agent administration provoked alterations (AT) in the tissue's optical characteristics.
- the curve (NATC) corresponds to an area where no alteration took place (NAT).
- the pseudocolor image of the phenomenon's kinetics (KI), which expresses the spatial distribution of one or more parameters, can be overimposed (after being calculated) on the tissue image, which is displayed in real-time on the monitor.
- the using the overimposed image as a guide facilitates substantially the determination of the lesion's boundaries, for successful surgical removal of the entire lesion, or for locating suspicious areas in order to obtain a biopsy sample(s).
- the measured quantitative data and the parameters that derive from them can constitute quantitative clinical indices for the in vivo staging of the lesion or of sub-areas of the latter.
- the simultaneous imaging in more than one spectral bands can assist in minimizing the contribution of the unwanted endogenous scattering, fluorescence and reflection of the tissue, to the optical signal captured by the detector.
- the captured optical signal comprise the optical signal generated by the marker-tissue interaction and the light emitted from the endogenous components of the tissue.
- the recorded response of the components of the tissue constitute noise, since it occludes the generated optical signal, which caries the diagnostic information. Therefore, separation of these signals, based on their particular spectral characteristics, will result in the maximization of the signal-to-noise ratio and consequently in the improvement of the obtained diagnostic information.
- FIG. 2 illustrates a method for capturing in two spectral bands simultaneously and in any spatial point of the area under analysis, the kinetics of the alterations in the characteristics of the remitted from the tissue light, before and the after the administration of the contrast enhancing agent.
- the remitted from the tissue light is collected and focused by the optical imaging module (L) and passes through a beam splitting (BSP) optical element.
- BSP beam splitting
- two identical images of the tissue (T) are generated, which can be captured by two detectors (D 1 , D 2 ).
- appropriate optical filters (Of ⁇ 1 ), (Of ⁇ 2 ) can be placed, so that images with different spectral characteristics are captured.
- the detectors (D 1 ), (D 2 ) are synchronized so that they capture simultaneously the corresponding spectral images of the tissue (Ti ⁇ 1 ), (Ti ⁇ 2 ) and in successive time-intervals, which are stored in the computer's data storage means.
- multiple spectral images can be captured simultaneously by combining multiple splitting elements, filters and sources.
- FIG. 3 illustrates another method for capturing in different spectral bands simultaneously and in any spatial point of the area under analysis, the kinetics of the alterations in the characteristics of the remitted from the tissue light, before and the after the administration of the contrast enhancing agent.
- MIP prism
- imaging optics it is possible to form multiple copies of the same image onto the surface of the same detector (D).
- Various optical filters OF ⁇ 1 ),(OF ⁇ 2 ),(OF ⁇ 3 ),(OF ⁇ 4 ), can be interposed along the length of the optical path of the rays that form the copies of the object's image, so that the captured multiple images correspond to different spectral areas.
- the different implementations of image capturing module described above can be integrated to conventional optical imaging diagnostic devises.
- Such devises are the various medical microscopes, colposcopes and endoscopes, which are routinely used for the in vivo diagnostic inspection of tissues. Imaging of internal tissues of the human body requires in most cases the illumination and imaging rays to travel along the same optical path, through the cavities of the body. Due to this fact, in the common optical diagnostic devises the tissue's surface reflection contributes substantially in the formed image. This limits the imaging information for the subsurface characteristics, which are in general of great diagnostic importance.
- FIG. 4 illustrates a schematic diagram of a medical microscope consisted from a light source (LS), a magnification selection mechanism (MS), an eyepiece (EP) and a mount for attaching the image capturing module (CA), (detector(s), readout electronics etc).
- LS light source
- MS magnification selection mechanism
- EP eyepiece
- CA image capturing module
- CA image capturing module
- TS surface reflected light
- the other linear polarizer By interposing the other linear polarizer to the optical path of the rays that are remitted from the tissue and form the optical image of the object, with its polarization plane perpendicular to the polarization level of the incident to the tissue light (IPO), the contribution of the surface reflection to the image of the object is eliminated.
- the light which is not surface-reflected enters the tissue, where due to multiple scattering, light polarization is randomized.
- a portion of the re-emitted light passes through the imaging polarization optics, carrying improved information for the subsurface features.
- FIG. 5 illustrates an endoscope consisted of an eyepiece (EP), which can be adapted to an electronic imaging system, optical fibers or crystals for the transmission of both illumination and image rays, optics for the linear polarization of light, one interposed to the optical path of the illumination rays (LE) and one to the path of the ray that form the optical image of the tissue (II).
- the polarization plane of the polarizing optics which are adapted to the exit of light from the endoscope (LPO), is perpendicular to the polarization plane of the polarizer, which is adapted to the point where the light enters the endoscope (IL).
- the polarization optics of the incident to the tissue light could also be adapted at the point where the light enters the endoscope (IL) but in this case, the endoscope has to be constructed using polarization preserving crystals or fiber optics for transferring the light. If polarization preserving light transmission media are used, then the polarizing optics of the imaging rays can be interposed in their path and before or after the eyepiece (EP).
- a problem for the effective clinical implementation of the described method herein is the micro-movements of the patient, which are always present during the snapshot imaging of the same tissue area. Obviously this problem is eliminated in case that the patient is under anesthesia (open surgery). In most cases however the movements of the tissue relative to the image capturing module, occurring during the successive image capturing time-course, have the consequence that the image pixels, with the same image coordinates, do not correspond to exactly the same spatial point x,y of the tissue area under examination.
- FIG. 6 A colposcopic apparatus is illustrated in FIG. 6, consisted of an articulated arm (AA), onto which the optical head (OH) is affixed, which includes a light source (LS), an objective lens (OBJ), an eye-piece (EP) and optics for selecting the magnification (MS).
- AA articulated arm
- OBJ objective lens
- EP eye-piece
- MS magnification
- the image capturing module is attached to the optical head (OH), through an opto-mechanical adapter.
- the speculum enters the vagina and its blades are opened up compressing the side walls of the vagina.
- the Speculum (KD) been mechanically connected with the optical head (OH), transfer any micromovement of the patient to the optical head (OH), which been mounted on an articulated arm (AA), follows these movements.
- the relative position between tissue and optical head remains almost constant.
- FIG. 6 illustrates an atomizer (A) attached to the optical head of the microscope.
- the unit (MIC) is comprised of electronics for controlling the agent sprayer and it can incorporate also the container for storing the agent.
- the unit (MIC) receives the proper command from the computer it sprays a predetermined amount of the agent onto the tissue surface, while the same or another command initiates the snapshot image capturing procedure.
- the illuminator of the imaging apparatus emits linearly polarized light
- the multiple reflections are randomizing the polarization plane of the incident light.
- the incident to the tissue under analysis light is not linearly polarized, then the elimination of the contribution of the surface reflection to the captured image can not be effective.
- FIG. 7 illustrates an optical imaging apparatus which comprises a light source located at the central part of its front-aperture.
- the central ray of the emitted light cone is coaxial, with the central ray of the light beam that enters the imaging apparatus.
- a reflective-objective lens is used, consisted at least of a first reflection ( 1 RM) and a second reflection ( 2 RM) mirror, where at the rear part of the first reflection mirror ( 2 RM), a light source (LS) is attached together (if required) with optics for light beam manipulation such as zooming and focusing (SO).
- the reflective objective lens by replacing the common refractive-objective, which is used in conventional microscopes, provides imaging capability in cavities of small diameter, with freedom in choosing the working distance.
- the zooming and focusing optics of the light beam can be adjusted simultaneously with the mechanism for varying the magnification of the optical imaging system, so that the illumination area and the field-of-view of the imaging system, are varying simultaneously and proportionally. This has as a result, the preservation of image brightness regardless of the magnification level of the lens.
- the imaging-illumination geometry embodied in this optical imaging apparatus among with the light beam manipulation options, enable the efficient elimination of the contribution of the surface reflection to the captured image and consequently the efficient clinical implementation of the method described herein.
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Priority Applications (25)
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US10/240,367 US7515952B2 (en) | 2000-03-28 | 2001-03-28 | System for characterization and mapping of tissue lesions |
EP09001994.4A EP2057936B1 (fr) | 2000-03-28 | 2001-03-28 | Procédé et système pour la caractérisation et la cartographie des lésions de tissu |
ES09001994.4T ES2464718T3 (es) | 2000-03-28 | 2001-03-28 | Método y sistema para caracterización y cartografía de lesiones tisulares |
AU4442301A AU4442301A (en) | 2000-03-28 | 2001-03-28 | Method and system for characterization and mapping of tissue lesions |
RU2002128728/14A RU2288636C2 (ru) | 2000-03-28 | 2001-03-28 | Способ и системы для определения параметров и картографирования поражений ткани |
DE60137914T DE60137914D1 (de) | 2000-03-28 | 2001-03-28 | Verfahren und vorrichtung zur charakterisierung und abbildung von gewebeläsionen |
EP01917343A EP1267707B1 (fr) | 2000-03-28 | 2001-03-28 | Procede et systeme de caracterisation et de cartographie de lesions de tissu |
AT01917343T ATE424757T1 (de) | 2000-03-28 | 2001-03-28 | Verfahren und vorrichtung zur charakterisierung und abbildung von gewebeläsionen |
BRPI0108944A BRPI0108944B8 (pt) | 2000-03-28 | 2001-03-28 | método para monitoramento dos efeitos de um agente diferenciador na patologia de uma amostra de tecido e sistema para caracterização e mapeamento de lesões do tecido. |
CNB018073522A CN100413460C (zh) | 2000-03-28 | 2001-03-28 | 组织病灶的表征和绘图的方法和系统 |
CA2400702A CA2400702C (fr) | 2000-03-28 | 2001-03-28 | Procede et systeme de caracterisation et de cartographie de lesions de tissu |
PCT/GR2001/000017 WO2001072214A1 (fr) | 2000-03-28 | 2001-03-28 | Procede et systeme de caracterisation et de cartographie de lesions de tissu |
JP2001570178A JP4217403B2 (ja) | 2000-03-28 | 2001-03-28 | 組織病巣の特徴付けおよびマッピングのためのシステム |
ES01917343T ES2322235T3 (es) | 2000-03-28 | 2001-03-28 | Metodo y sistema para caracterizacion y cartografia de lesiones tisulares. |
PT01917343T PT1267707E (pt) | 2000-03-28 | 2001-03-28 | Método e sistema para caracterização e mapeamento de lesões de tecido |
PT90019944T PT2057936E (pt) | 2000-03-28 | 2001-03-28 | Método e sistema para caracterização e mapeamento de lesões de tecido |
DK01917343T DK1267707T3 (da) | 2000-03-28 | 2001-03-28 | Metode og system til karakterisering og kartografi af vævslesioner |
FI20021477A FI20021477A (fi) | 2000-03-28 | 2002-08-14 | Menetelmä ja järjestelmä kudosleesioiden karakterisoimiseksi ja kartoittamiseksi |
US10/346,338 US20030163049A1 (en) | 2000-03-28 | 2003-01-16 | Method and system for characterization and mapping of tissue lesions |
HK03108410.2A HK1056108A1 (en) | 2000-03-28 | 2003-11-19 | Method and system for characterization and mapping of tissue lesions |
US10/850,955 US20050054936A1 (en) | 2000-03-28 | 2004-05-21 | Method and system for characterization and mapping of tissue lesions |
US10/978,101 US8173432B2 (en) | 2000-03-28 | 2004-10-29 | Method and system for characterization and mapping of tissue lesions |
US11/266,021 US7598088B2 (en) | 2000-03-28 | 2005-11-03 | Optical imaging method and system for characterization and mapping of tissue lesions |
JP2008115094A JP2008220977A (ja) | 2000-03-28 | 2008-04-25 | 組織病巣の特徴付けおよびマッピングのための方法およびシステム |
CY20091100583T CY1109134T1 (el) | 2000-03-28 | 2009-06-01 | Μεθοδος και συστημα χαρακτηρισμου και χαρτογραφησης αλλοιωσεων των ιστων |
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US10/240,367 Expired - Lifetime US7515952B2 (en) | 2000-03-28 | 2001-03-28 | System for characterization and mapping of tissue lesions |
US10/346,338 Abandoned US20030163049A1 (en) | 2000-03-28 | 2003-01-16 | Method and system for characterization and mapping of tissue lesions |
US10/850,955 Abandoned US20050054936A1 (en) | 2000-03-28 | 2004-05-21 | Method and system for characterization and mapping of tissue lesions |
US10/978,101 Expired - Fee Related US8173432B2 (en) | 2000-03-28 | 2004-10-29 | Method and system for characterization and mapping of tissue lesions |
US11/266,021 Expired - Fee Related US7598088B2 (en) | 2000-03-28 | 2005-11-03 | Optical imaging method and system for characterization and mapping of tissue lesions |
US12/368,647 Expired - Fee Related US7974683B2 (en) | 2000-03-28 | 2009-02-10 | Method and system for characterization and mapping of tissue lesions via light and special chemical agents |
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US10/240,367 Expired - Lifetime US7515952B2 (en) | 2000-03-28 | 2001-03-28 | System for characterization and mapping of tissue lesions |
US10/346,338 Abandoned US20030163049A1 (en) | 2000-03-28 | 2003-01-16 | Method and system for characterization and mapping of tissue lesions |
US10/850,955 Abandoned US20050054936A1 (en) | 2000-03-28 | 2004-05-21 | Method and system for characterization and mapping of tissue lesions |
US10/978,101 Expired - Fee Related US8173432B2 (en) | 2000-03-28 | 2004-10-29 | Method and system for characterization and mapping of tissue lesions |
US11/266,021 Expired - Fee Related US7598088B2 (en) | 2000-03-28 | 2005-11-03 | Optical imaging method and system for characterization and mapping of tissue lesions |
US12/368,647 Expired - Fee Related US7974683B2 (en) | 2000-03-28 | 2009-02-10 | Method and system for characterization and mapping of tissue lesions via light and special chemical agents |
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EP (2) | EP2057936B1 (fr) |
JP (2) | JP4217403B2 (fr) |
CN (1) | CN100413460C (fr) |
AT (1) | ATE424757T1 (fr) |
AU (1) | AU4442301A (fr) |
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CA (1) | CA2400702C (fr) |
CY (1) | CY1109134T1 (fr) |
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DK (1) | DK1267707T3 (fr) |
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GR (1) | GR1004180B (fr) |
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PT (2) | PT2057936E (fr) |
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