Imaging system for combined full-color reflectance and near-infrared imaging

Information

  • Patent Grant
  • 9642532
  • Patent Number
    9,642,532
  • Date Filed
    Friday, October 2, 2015
    8 years ago
  • Date Issued
    Tuesday, May 9, 2017
    7 years ago
Abstract
An imaging system for acquisition of NIR and full-color images includes a light source providing visible light and NIR light to an area under observation, such as living tissue, a camera having one or more image sensors configured to separately detect blue reflectance light, green reflectance light, and combined red reflectance light/detected NIR light returned from the area under observation. A controller in signal communication with the light source and the camera is configured to control the light source to continuously illuminate area under observation with temporally continuous blue/green illumination light and with red illumination light and NIR excitation light. At least one of the red illumination light and NIR excitation light are switched on and off periodically in synchronism with the acquisition of red and NIR light images in the camera.
Description
FIELD OF THE INVENTION

The invention is directed to medical imaging, in particular to a system and method for obtaining visible light images and near infrared light images from an area under observation, such as living tissue, and in particular for use in endoscopy.


BACKGROUND OF THE INVENTION

Near-infrared (NIR) imaging has been described in the literature for various clinical applications. Typically such an imaging modality utilizes a contrast agent (e.g. indocyanine green) that absorbs and/or fluoresces in the NIR. Such contrast agents may be conjugated to targeting molecules (e.g. antibodies) for disease detection. The contrast agents may be introduced into tissue intravenously or subcutaneously to image tissue structure and function (e.g. flow of blood/lymph/bile in vessels) that is not easily seen with standard visible light imaging technology.


Independently of the clinical application, endoscopic NIR imaging devices typically include multiple imaging modes as a practical feature. For example, endoscopists utilize visible spectrum color for both visualization and navigation, and an endoscopic imaging device that offers NIR imaging typically provides a concurrent color image. Such concurrent imaging devices can be realized, for example, as follows:

    • One conventional configuration utilizes spectral separation of the visible and the NIR light, with full color and NIR image signals acquired using separate sensors for the different color (e.g. red, green, and blue) and NIR spectral bands or a single color sensor with an integrated filter with filter elements transparent to the different spectral bands (e.g. red, green, blue and NIR). Thus, such multi-modality color and NIR imaging devices provide dedicated sensors or sensor pixels for each of the two imaging modes. Disadvantageously, this increases the number of image sensors in multi-sensor implementations or compromises image resolution when on the same sensor, specific sensor pixels are dedicated for NIR imaging while others are utilized for color imaging.
    • Another conventional configuration utilizes a single monochrome image sensor for sequential imaging of the visible and NIR light. The object is hereby sequentially illuminated with light in the red, green, blue and NIR spectral bands, with separate image frames being acquired for each spectral band and composite color and NIR images being generated from the acquired image frames. However, this approach, where image frames are acquired sequentially at different times, can generate objectionable motion artifacts (i.e. color fringing and “rainbow effects”) in the composite color and NIR images. These artifacts can be mitigated by increasing the acquisition or frame rate to more than, for example, 15 frames/second (fps), for example to 90 fps, or even 180 fps. Because of the high data transfer rate, high frame rates are difficult to implement for high definition images (e.g. 2 million pixels), or images having a large dynamic range (>10 bits), thus limiting image size and/or resolution.


It would therefore be desirable to provide a system and a method for simultaneous acquisition of full-color visible light and NIR light images, which obviates the aforementioned disadvantages and does not compromise image resolution and/or introduce objectionable motion artifacts.


SUMMARY OF THE INVENTION

According to one aspect of the invention, a method for acquisition of NIR images and full-color images includes the steps of illuminating an area under observation with continuous blue/green light, and illuminating the area under observation with red light and NIR light, wherein at least one of the red light and NIR light are switched on and off periodically. The blue, green, red and NIR light returning from the area under observation is directed to one or more sensors which are configured to separately detect the blue light, the green light, and the combined red light/NIR light. The red light spectral component and the NIR light spectral component are determined separately from image signals of the combined red light/NIR light, in synchronism with the switched red and NIR light. A full-color reflectance image of the area under observation is rendered and displayed from the blue, green, and red light and an NIR image is likewise rendered and displayed from the NIR light.


According to another aspect of the invention, an imaging system for acquisition of NIR and full-color images includes a light source providing visible light and NIR light to an area under observation, a camera having one or more image sensors configured to separately detect blue and green light, and combined red and NIR light returned from the area under observation, and a controller in signal communication with the light source and the camera. The controller is configured to control the light source to continuously illuminate tissue with blue/green light and to illuminate the area under observation with red light and NIR light, wherein at least one of the red light and NIR light are switched on and off periodically in synchronism with the acquisition of the red and NIR images in the camera.


The controller is further configured to determine from sensor signals representing the combined red light and NIR light separately the red light spectral component and the NIR light spectral component. The imaging system further includes a display receiving image signals corresponding to the blue light, the green light, and the separately determined red light spectral component and rendering therefrom a full-color visible light image of the area under observation. The display also receives the separately determined NIR light spectral component and renders therefrom an NIR image of the area under observation.


The video imaging system may use a three-sensor color camera configured to continuously image the blue and green wavebands and intermittently image the red waveband, thus providing continuous, high quality luma information and a sufficiently continuous complete chroma to produce high quality video images of the area under observation, such as living tissue. In such a configuration, the red image sensor can be time-multiplexed to acquire both red and NIR images (i.e. the red image sensor alternately, and in rapid succession, images both red light for the color information required for the color image and NIR light for image information required for the NIR image). Such time-multiplexing may be coupled to (and synchronized with) the illumination source used to provide the NIR illumination (excitation for fluorescence) and the red light for color imaging. Image processing is then utilized to separate and process the resulting image signals appropriately.


Embodiments of the invention may include one or more of the following features. The area under observation may be alternatingly illuminated with red light and NIR light, wherein the duration of red light may be different from, preferably longer than, the duration of illumination with NIR light. The illumination may be switched at video field or frame rates.


Fields captured by the image sensor and lacking the red light spectral component or the NIR light spectral component may be interpolated from temporally adjacent image fields that include a corresponding red light spectral component or NIR light spectral component. In one embodiment, the NIR light spectral component obtained in the absence of red light may be subtracted from the combined red light/NIR light to obtain the separate red light spectral component. This is advantageous in particular when the detected NIR signal has an intensity comparable to that of the red signal.


In one embodiment, the light source may include an illuminator emitting a substantially constant intensity of visible light and NIR light over a continuous spectral range, and a plurality of movable filters disposed between the illuminator and the area under observation for transmitting temporally continuous blue/green light and temporally discontinuous red light and NIR light.


In another embodiment, the light source may include an illuminator emitting a substantially constant intensity of visible light and NIR light over a continuous spectral range, first dichroic means for separating the visible light and NIR light into blue/green and red light and NIR light, shutter means for transforming the separated red light and NIR light into temporally discontinuous red light and discontinuous NIR light, and second dichroic means for combining the blue/green light, the temporally discontinuous red light and the temporally discontinuous NIR light for transmission to the area under observation.


In yet another embodiment, the light source may include a first illuminator emitting a substantially constant intensity of green and blue light, a second illuminator producing switched red light, a third illuminator producing switched NIR excitation light, and dichroic means for combining the switched red light and the switched NIR light with the green and blue light for transmission to the area under observation. The switched red light and the NIR light may be produced by interrupting a continuous intensity light beam of the red light and the NIR light by a shutter or chopper. Alternatively, the switched red light and the NIR light may be produced by electrically switching the second illuminator and the third illuminator on and off.


The image sensors may employ an interlaced scan or a progressive scan.


The imaging system may include an endoscope.





BRIEF DESCRIPTION OF THE DRAWINGS

The following figures depict certain illustrative embodiments of the invention which are to be understood as illustrative of the invention and not as limiting in any way.



FIG. 1 shows an endoscopic system according to one embodiment of the invention;



FIGS. 2a-2d show various exemplary embodiments of a multimode light source to be used with the endoscopic system of FIG. 1;



FIG. 3a shows an exemplary dichroic prism employed by a 3-sensor color camera;



FIG. 3b shows the optical transmission ranges for the spectral components separated by the dichroic prism of FIG. 3a;



FIG. 3c shows the optical transmission range of a notch filter that blocks excitation light from entering the camera;



FIG. 4 shows a timing diagram of a first embodiment for continuous illumination with green/blue light and alternating illumination with red/NIR light;



FIG. 5 shows a timing diagram of a second embodiment for continuous illumination with green/blue light and alternating illumination with red/NIR light;



FIG. 6 shows a timing diagram of a third embodiment for continuous illumination with green/blue/NIR light and alternating illumination with red light; and



FIG. 7 shows an exemplary CMOS sensor having stacked imaging layers and the corresponding spectral sensitivity of these layers.





DESCRIPTION OF CERTAIN ILLUSTRATED EMBODIMENTS

Color video images are generally obtained with three-sensor color cameras where separate red, green and blue image sensors provide simultaneous contiguous arrays of red, green and blue pixel information. Full color video images are generated by combining the image information from all three sensors. Color fidelity (i.e. a true color rendition) is extremely important in medical imaging applications and all three sensors are used to provide complete color information.


To understand the relative importance of color and spatial information in video images of human tissue, however, it is useful to consider information in such video images in terms of luma and chroma. Luma refers to the brightness information in the image and it is this information that provides the spatial detail that enables the viewer to recognize shapes. The spatial and temporal resolution of luma is consequently crucial to the perception of video image quality. Chroma refers to the color information in the video image. It is a property of human vision that fine detail variations in the chroma of image features are not easily perceived and that such variations are consequently less critical than fine detail variations in luma, in an overall assessment of image quality. It is for this reason that video encoding of chroma information is often sub-sampled.


In video images of human tissue obtained with visible light, the structural details of the tissue are largely contained in the blue and green wavelength regions of the imaged light. Blue and green light tends to be reflected from the tissue surface, whereas red light tends to be highly scattered within the tissue. As a consequence, there is very little fine structural detail in the red light that reaches the red image sensor. It is also known from color science that human vision receives most of the spatial information from the green portion of the visible spectrum—i.e. green light information contributes disproportionately to the luma. The standard formula for calculating luma from gamma-corrected color components is Y′=0.2126 R′+0.7152 G′+0.0722 B′. For this reason, spatial and/or temporal interpolation of the red component of video images of human tissue does not significantly affect perception of fine detail in those images.


Similarly to red light, NIR light tends to be scattered in tissue causing NIR image features to be diffusely, rather than sharply defined. Furthermore, because the NIR image highlights areas of interest (i.e. the areas in which the contrast agent is localized), but does not provide the overall visualization or navigational information, it is desirable for a NIR endoscopic imaging device to provide a continuous color image and either a superimposed or side-by-side display of the NIR image information. In such a display the NIR light would also contribute less to the spatial information presented to observer.



FIG. 1 shows schematically an exemplary embodiment of a NIR endoscopic imaging system 10 which includes a multimode light source 11 that provides both visible and NIR illumination, connected to an endoscope 12 by way of an illumination guide, for example a fiber optic cable 17, suitable for transmission of both color and NIR illumination, a color camera 13, illustrated here as having three different sensors 34, 36, 38 (see FIG. 3a) for blue, green and red/NIR imaging, respectively, mounted to the endoscope image guide, and a camera controller 14 connected to the camera 13 and the light source 11 for controlling and synchronizing illumination and image acquisition. Controller 14 can also process the acquired visible and NIR images for display on a monitor 15 connected to the controller 14, for example, by a cable 19. Images can be acquired in real time at selectable frame rates, such as video rates.



FIGS. 2a-2d show schematic diagrams of exemplary embodiments of various light sources 11. The illustrated light sources are constructed to supply in normal color imaging mode visible illumination light yielding a substantially continuous spectral distribution. The light source maybe an arc lamp, a halogen lamp, one or more solid state sources (e.g. LEDs, semiconductor lasers) or any combination thereof and may be spectrally filtered or shaped (e.g. with bandpass filters, IR filters, etc.). The continuous spectrum may be produced as primary colors (RGB) either concurrently or sequentially, for example, using a rotating filter wheel.


In systems according to the present invention, light sources to be used with the system of the invention and described in detail below are configured to provide continuous, uninterrupted illumination in the blue and green parts of the visible spectrum and discontinuous red and/or NIR light. The blue and green parts of the visible spectrum may be optically filtered from the emission produced by a continuous source or produced directly by a narrow-band source (e.g. blue and green LEDs). The red and NIR light may also be produced by an arc lamp, a halogen lamp, a solid state source (e.g., red and NIR LEDs or lasers), or any combination thereof.


Turning now to FIG. 2a, in one embodiment a light source 11a includes an illuminator 202 producing visible and NIR light emission, a collimating lens 204, a filter wheel or reciprocating filter holder 208 that alternatingly transmits red and NIR light and continuously transmits green and blue light. Alternatively, a tunable electro-optic or acousto-optic filter may be used. The filtered light is focused by lens 206 onto light guide 17.


Another embodiment of a light source 11b is schematically illustrated in FIG. 2b. The light source 11b includes an illuminator 202 producing visible and NIR light emission and a collimating lens 204. A dichroic mirror 212 transmits green/blue light and reflects red/NIR light to another dichroic mirror 214 which transmits NIR light to NIR mirror 215 and reflects red light, or vice versa. The green/blue light can be further bandpass-filtered by filter 213. The reflected red and NIR light is chopped, for example, by chopper wheels 219a, 219b (which can be combined into a single chopper wheel) to produce temporally discontinuous illumination, which is then reflected by mirrors 216, 217 and combined with the green/blue light by dichroic mirror 218. The combined light is then focused by lens 206 onto light guide 17, as before.


In another embodiment of a light source 11c schematically illustrated in FIG. 2c, an illuminator 202a produces green and blue light emission which is collimated by a collimating lens 204a. Likewise, separate illuminators 202b, 202c produce respective red and NIR light emissions which are collimated by corresponding collimating lenses 204b and 204c. As in the embodiment of FIG. 2b, the red and NIR light is chopped, for example, by chopper wheels 219a, 219b (which may also be combined into a single chopper wheel) to produce temporally discontinuous illumination, which is then combined with the green/blue illumination by dichroic mirrors 222, 228. The combined light is then focused by lens 206 onto light guide 17, as before.


In yet another embodiment of a light source 11d schematically illustrated in FIG. 2d, an illuminator 202a produces green and blue light emission which is collimated by a collimating lens 204a, as before. However, unlike in the embodiment of FIG. 2c, the separate illuminators 202d, 202e are here switched electrically to produce red and NIR light emissions with controlled timing. For example, the red and NIR light sources 202d, 202e may be solid state light sources, such as LEDs or semiconductor lasers, which can be rapidly turned on and off with suitable, preferably electronic, switches. As described above with reference to FIG. 2c, the red and NIR illumination is collimated by corresponding collimating lenses 204b and 204c and combined with the green/blue illumination by dichroic mirrors 222, 228. The combined light is then focused by lens 206 onto light guide 17, as before.


The alternating red and NIR illumination is synchronized with the image acquisition of the three-sensor camera such that red and NIR images are acquired by the camera synchronously with the red and NIR illumination of the endoscope.



FIG. 3a shows in more detail the three-sensor camera 13 of FIG. 1, in particular the optical beam splitter used to direct red/NIR, green, and blue light to the three different image sensors 34, 36 and 38, respectively. For NIR fluorescence applications, the camera preferably also includes an excitation band blocking filter 32. The beam splitter may be made, for example, of a plurality of dichroic prisms, cube splitters, plate splitters or pellicle splitters. FIG. 3b shows the spectral composition of the light received from the endoscope according to FIG. 3a. FIG. 3c illustrates the spectral composition of the light transmitted through the excitation band blocking filter 32 implemented as a notch filter 31 which blocks transmission of excitation light, while transmitting the other wavelengths in the visible and NIR spectral range. The transmission characteristic of this filter 32 may be designed to also block undesired NIR wavelengths interfering with the visible spectrum that may degrade the color image.



FIG. 4 shows a timing diagram for a first exemplary embodiment of a simultaneous color and NIR imaging mode using, for example, a three-sensor camera. In this embodiment, the camera sensors utilize an interlaced read-out format which represents an advantageous combination of spatial and temporal resolution for smooth display of motion. Any of the light sources illustrated in FIGS. 2a-2d can be used with this embodiment. The light source provides continuous blue/green illumination and alternating red and NIR illumination. Half-frames are alternatingly exposed on the image sensors, i.e., a first field (half-frame) with even lines alternating with a second field (half-frame) with odd lines. In the timing diagram of FIG. 4 depicting a full frame rate of 30 fps, one field period (16.7 ms) provides NIR illumination, followed by two field periods (33.3 ms) of red illumination. Stated differently, the sample or tissue is illuminated with full-spectrum color (RGB) during two field periods (33.3 ms) and with GB and NIR during a third field period. For reconstructing the full-color visible image, the missing red information is interpolated between the fields adjacent to the field with the NIR illumination. The blue and green image information is always available, thereby providing optimum and continuous luma information. The NIR image is generated from every sixth field in each half frame, wherein the missing lines are spatially interpolated. When the fluorescence field is displayed, the image is updated every three fields, with the displayed image interpolated between even and odd lines.


In all the figures, the term “IR” is used instead of or interchangeably with “NIR.”


Once the color and NIR image data have been processed, the signal is outputted to a video monitor and may be displayed as two separate, simultaneous views (one color and one fluorescence) or as combined color and fluorescence image signals (e.g. by assigning the fluorescence signal a color that contrasts with the naturally occurring colors in the tissue).



FIG. 5 shows a timing diagram for a second exemplary embodiment of a simultaneous color and NIR imaging mode. In this embodiment, the camera sensors utilize a progressive scan sensor read-out format wherein a complete frame (G/B/R alternating with G/B/NIR) is read out during each field period. Any of the light sources illustrated in FIGS. 2a-2d can be used with this embodiment. The light source provides continuous blue/green illumination and alternating red and NIR illumination. In the timing diagram of FIG. 5, one field period (16.7 ms) provides NIR illumination, followed by one field period (16.7 ms) of red illumination. Stated differently, the sample or tissue is illuminated with full-spectrum color (RGB) during one field period (16.7 ms) and with GB and NIR during a third field period. In this case, a full visible spectrum color image is available at every pixel, in every other frame. In the alternate frames, the blue and green information is acquired directly, whereas the red information is interpolated between adjacent frames. Unlike with the embodiment of FIG. 4, no spatial interpolation is required. Further image processing and display can be implemented in a manner similar to that described in previous embodiments.



FIG. 6 shows a timing diagram for a third exemplary embodiment, wherein both the green/blue illumination and the NIR illumination are continuous, while only the red illumination is modulated. Like in the embodiment of FIG. 4, half-frames are alternatingly exposed on the image sensors, i.e., a first field (half-frame) with even lines alternating with a second field (half-frame) with odd lines. In the timing diagram of FIG. 6 depicting a full frame rate of 30 fps, one field period (16.7 ms) provides (NIR+GB) illumination (red illumination switched off), followed by two field periods (33.3 ms) of (NIR+RGB). If the NIR image signal is small compared to the red reflected signal, it will not significantly affect the overall visible (RGB) image, so that the color image may be generated by conventional color image processing without correction. Otherwise the NIR contribution obtained in the red image channel when the red illumination is switched off may be subtracted from the (NIR+R) image data by spatial and temporal interpolation to obtain the red image signal, as shown in the second to last lien in the timing diagram of FIG. 6. Alternatively, sensors with a progressive scan image sensor readout similar to those illustrated in FIG. 5 could be used with RGB and (RGB+IR) image acquisition in alternate frames.


In yet another exemplary embodiment (not illustrated in the drawings), the green/blue illumination as well as the red illumination are continuous, whereas the NIR illumination is modulated. This timing scheme can be best applied if the red and NIR image signals have approximately the same magnitude. In this embodiment, the light source provides uninterrupted illumination with full visible spectrum and intermittent illumination with NIR light. The timing diagram is essentially the same as that depicted in FIG. 6, with the NIR and the red illumination interchanged. The intermittent NIR illumination is synchronized to coincide with every 3rd field with interlaced cameras and with every other field in progressive scan cameras. For every field in which NIR illumination is provided, the red image sensor will acquire a (R+NIR) image signal. The NIR image signal can be extracted from the (R+NIR) image signal by interpolation of the red signal value from the appropriate preceding and subsequent “red only” image fields and subtracting the red image signal from the (R+NIR) signal. Since the red and NIR image signals are of similar magnitude, such interpolation and subtraction will provide a reasonably accurate NIR image signal value. The color image is processed by using the acquired and interpolated values for the red image signal in combination with the blue and green image signals. The resulting color and NIR image information can then be displayed or recorded as described before.


In any of the aforementioned embodiments, the NIR endoscopic imaging system can also be operated such that the light sources provides continuous illumination with either the full visible spectrum or the NIR spectrum and the camera acquires the corresponding color image or NIR (absorbance or fluorescence) image in a continuous fashion to provide high spatial resolution. The resulting video image of either individual illumination/imaging mode—color or NIR—can be subsequently displayed and/or recorded.


By implementing color and NIR imaging as described in the aforementioned embodiments, it is possible to acquire and display full-color visible light and NIR light images at video rates without compromising image resolution and/or introducing objectionable motion artifacts. Furthermore, should any residual color fringing occur as a consequence of sharp edges moving rapidly across the visual field (e.g. with the discontinuous acquisition of red or NIR images), these relatively minor effects can be mitigated by temporal interpolation of the missing (red/NIR) video fields with minimum additional processing time.


While the invention has been disclosed in connection with the preferred embodiments shown and described in detail, various modifications and improvements thereon will become readily apparent to those skilled in the art. For example, instead of using separate image sensors for G/B and R/NIR, or a single color sensor for RGB images and NIR fluorescence images, a single direct three-color RGB sensor image sensor with a stacked pixel design implemented in CMOS technology and commercially available from Foveon, Inc., San Jose, Calif., may be used. Such sensor is schematically illustrated in FIG. 7. It will be understood that this sensor design can be extended to four colors by adding an NIR-sensitive layer. The red, green, blue and NIR images are hereby acquired at different depths in the image sensor. With a 4-layer sensor, multiplexing of the red and NIR illumination would be unnecessary. However, with a 3-layer sensor, the red and NIR illumination would still need to be multiplexed, as described above for a 3-sensor conventional camera. An appropriate barrier filter to block the NIR excitation light would also be required for fluorescence imaging applications.


While the invention has been illustrated and described in connection with currently preferred embodiments shown and described in detail, it is not intended to be limited to the details shown since various modifications and structural changes may be made without departing in any way from the spirit and scope of the present invention. The embodiments were chosen and described in order to explain the principles of the invention and practical application to thereby enable a person skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated.

Claims
  • 1. An imaging system for acquisition of NIR images and full-color images comprising: a light source providing visible light and NIR light to an area under observation, the visible light comprising blue illumination light, green illumination light, and red illumination light, the blue illumination light being reflected from the tissue as blue reflectance light, the green illumination light being reflected from the tissue as green reflectance light, and the red illumination light being reflected from the tissue as red reflectance light;a camera having one or more image sensors;a controller in signal communication with the light source and the camera for illuminating the area under observation with the blue illumination light continuously and illuminating the area under observation with the red illumination light and the NIR illumination light, wherein at least one of the red illumination light and NIR illumination light is switched on and off periodically according to a predetermined timing scheme, and simultaneously acquiring a first image signal corresponding to the blue illumination light, a second image signal corresponding to the green illumination light, and a third image signal corresponding to the red illumination light and NIR illumination light; anddetermining the red reflectance light and detected NIR light from the third image signal, based on the timing scheme, andwherein the imaging system is configured to generate the full-color reflectance and NIR images of the area under observation.
  • 2. The imaging system of claim 1, wherein the area under observation is alternatingly illuminated by the light source with red illumination light and NIR illumination light.
  • 3. The imaging system of claim 1, wherein the light source comprises an illuminator emitting a substantially constant intensity of visible light and NIR light over a continuous spectral range, anda plurality of filters disposed between the illuminator and the area under observation for transmitting temporally continuous blue light and temporally discontinuous red light and discontinuous NIR light.
  • 4. The imaging system of claim 1, wherein the light source comprises an illuminator emitting a substantially constant intensity of visible light and NIR light over a continuous spectral range,first dichroic means for separating the visible light and NIR light into blue and red light and NIR light,shutter means for transforming the separated red light and NIR light into temporally discontinuous red light and discontinuous NIR light, andsecond dichroic means for combining the blue light, the temporally discontinuous red light and the temporally discontinuous NIR light for transmission to the area under observation.
  • 5. The imaging system of claim 1, wherein the light source comprises a first illuminator emitting a substantially constant intensity of green and blue light,a second illuminator producing switched red light,a third illuminator producing switched NIR light, anddichroic means for combining the switched red light and the switched NIR light with the green and blue light for transmission to the area under observation.
  • 6. The imaging system of claim 5, wherein the switched red light and the NIR light are produced by interrupting a continuous intensity light beam of the red light and the NIR light by a shutter or chopper.
  • 7. The imaging system of claim 5, wherein the switched red light and the NIR light are produced by electrically switching the second illuminator and the third illuminator on and off.
  • 8. The imaging system of claim 1, wherein the one or more image sensors are configured to employ an interlaced scan.
  • 9. The imaging system of claim 1, wherein the predetermined timing scheme includes alternating the red illumination light and NIR illumination light.
  • 10. The imaging system of claim 9, wherein the duration of illumination with the red illumination light is longer than the duration of illumination with the NIR illumination light.
  • 11. The imaging system of claim 1, where the controller controls the light source such that the green illumination light continuously illuminates the area under observation.
  • 12. The imaging system of claim 1, wherein the camera comprises a single sensor.
  • 13. The imaging system of claim 12, wherein the single sensor comprises a three-color RGB sensor.
  • 14. The imaging system of claim 1, wherein the light source comprises one or more solid state sources.
  • 15. The imaging system of claim 1, wherein the blue, green, and red illumination light are produced by blue, green, and red LEDs, respectively.
  • 16. The imaging system of claim 1, wherein the one or more image sensors comprise a single image sensor having pixels, each pixel responsive to one of the blue reflectance light, the green reflectance light, and the red reflectance light and NIR light returned from the area under observation.
  • 17. The imaging system of claim 16, wherein the single image sensor comprises a mosaic filter array.
  • 18. The imaging system of claim 1, wherein the imaging system is configured as an endoscope.
  • 19. The imaging system of claim 1, wherein the NIR light detected by the camera is fluorescent light.
CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation Application of U.S. application Ser. No. 12/933,512 filed on Nov. 24, 2010, now U.S. Pat. No. 9,173,554, which is a U.S. national phase application of PCT/US2009/037506, having an international filing date of Mar. 18, 2009, which claims the benefit of U.S. Provisional Application No. 61/037,514, filed on Mar. 18, 2008. The prior applications, including the specifications, drawings and abstract are incorporated herein by reference in their entirety.

US Referenced Citations (314)
Number Name Date Kind
1290744 Hollander Jan 1919 A
2453336 Orser Nov 1948 A
2857523 Corso Oct 1958 A
3215029 Woodcock Nov 1965 A
3582178 Boughton et al. Jun 1971 A
3671098 Rotter Jun 1972 A
3749494 Hodges Jul 1973 A
3790248 Kellow Feb 1974 A
3931593 Marshall Jan 1976 A
3970373 Pledger Jul 1976 A
3971068 Gerhardt et al. Jul 1976 A
4037866 Price Jul 1977 A
4066330 Jones Jan 1978 A
4115812 Akatsu Sep 1978 A
4149190 Wessler et al. Apr 1979 A
4158504 de Ponteves et al. Jun 1979 A
4200801 Schuresko Apr 1980 A
4260217 Traeger et al. Apr 1981 A
4318395 Tawara Mar 1982 A
4355325 Nakamura et al. Oct 1982 A
4378571 Handy Mar 1983 A
4449535 Renault May 1984 A
4471766 Terayama Sep 1984 A
4532918 Wheeler Aug 1985 A
4556057 Hiruma et al. Dec 1985 A
4575632 Lange Mar 1986 A
4597630 Brandstetter et al. Jul 1986 A
4611888 Prenovitz et al. Sep 1986 A
4638365 Kato Jan 1987 A
4660982 Okada Apr 1987 A
4688905 Okamura Aug 1987 A
4717952 Kohayakawa et al. Jan 1988 A
4742388 Cooper et al. May 1988 A
4768513 Suzuki Sep 1988 A
4786813 Svanberg et al. Nov 1988 A
4799104 Hosoya et al. Jan 1989 A
4806005 Schneider et al. Feb 1989 A
4821117 Sekiguchi Apr 1989 A
4837625 Douziech et al. Jun 1989 A
4852985 Fujihara et al. Aug 1989 A
4856495 Tohjoh et al. Aug 1989 A
4895145 Joffe Jan 1990 A
4930516 Alfano et al. Jun 1990 A
4930883 Salzman Jun 1990 A
4951135 Sasagawa et al. Aug 1990 A
4953539 Nakamura et al. Sep 1990 A
4954897 Ejima et al. Sep 1990 A
4974936 Ams et al. Dec 1990 A
5001556 Nakamura et al. Mar 1991 A
5007408 Ieoka Apr 1991 A
5028128 Onuki Jul 1991 A
5034888 Uehara et al. Jul 1991 A
5041852 Misawa et al. Aug 1991 A
5115308 Onuki May 1992 A
5121220 Nakamoto Jun 1992 A
5128803 Sprafke Jul 1992 A
5132837 Kitajima Jul 1992 A
5134662 Bacus et al. Jul 1992 A
5165079 Schulz-Hennig Nov 1992 A
5205280 Dennison, Jr. et al. Apr 1993 A
5208651 Bulcan May 1993 A
5214503 Chiu et al. May 1993 A
5225883 Carter et al. Jul 1993 A
5255087 Nakamura et al. Oct 1993 A
5278642 Danna et al. Jan 1994 A
5282082 Espie et al. Jan 1994 A
5295017 Brown Mar 1994 A
RE34622 Ledley May 1994 E
5365057 Morley et al. Nov 1994 A
5371355 Wodecki Dec 1994 A
5377686 O'Rourke et al. Jan 1995 A
5379756 Pileski et al. Jan 1995 A
5408263 Kikuchi et al. Apr 1995 A
5410363 Capen et al. Apr 1995 A
5419323 Kittrell et al. May 1995 A
5420628 Poulsen et al. May 1995 A
5421337 Richards-Kortum et al. Jun 1995 A
5424841 Van Gelder et al. Jun 1995 A
5426530 Copenhaver et al. Jun 1995 A
5430476 Hafele et al. Jul 1995 A
5481401 Kita et al. Jan 1996 A
5485203 Nakamura et al. Jan 1996 A
5490015 Umeyama et al. Feb 1996 A
5507287 Palcic et al. Apr 1996 A
5515449 Tsuruoka et al. May 1996 A
5535052 Jörgens Jul 1996 A
5536236 Yabe et al. Jul 1996 A
5557451 Copenhaver et al. Sep 1996 A
5585846 Kim Dec 1996 A
5590660 MacAulay et al. Jan 1997 A
5596654 Tanaka Jan 1997 A
5646680 Yajima Jul 1997 A
5647368 Zeng et al. Jul 1997 A
5647840 D'Amelio et al. Jul 1997 A
5667472 Finn et al. Sep 1997 A
5677724 Takizawa et al. Oct 1997 A
5682567 Spruck et al. Oct 1997 A
5689354 Orino Nov 1997 A
5695049 Bauman Dec 1997 A
5697373 Richards-Kortum et al. Dec 1997 A
5713364 DeBaryshe et al. Feb 1998 A
5729382 Morita et al. Mar 1998 A
5749830 Kaneko et al. May 1998 A
5769792 Palcic et al. Jun 1998 A
5772355 Ross et al. Jun 1998 A
5772580 Utsui et al. Jun 1998 A
5827190 Palcic et al. Oct 1998 A
5833617 Hayashi Nov 1998 A
5838001 Minakuchi et al. Nov 1998 A
5840017 Furusawa et al. Nov 1998 A
5852498 Youvan et al. Dec 1998 A
5891016 Utsui et al. Apr 1999 A
5897269 Ross et al. Apr 1999 A
5971918 Zanger Oct 1999 A
5973315 Saldana et al. Oct 1999 A
5984861 Crowley Nov 1999 A
5986271 Lazarev et al. Nov 1999 A
5986642 Ueda et al. Nov 1999 A
5990996 Sharp Nov 1999 A
5999240 Sharp et al. Dec 1999 A
6002137 Hayashi Dec 1999 A
6004263 Nakaichi et al. Dec 1999 A
6008889 Zeng et al. Dec 1999 A
6021344 Lui et al. Feb 2000 A
6028622 Suzuki Feb 2000 A
6030339 Tatsuno et al. Feb 2000 A
6059719 Yamamoto et al. May 2000 A
6059720 Furusawa et al. May 2000 A
6061591 Freitag et al. May 2000 A
6069689 Zeng et al. May 2000 A
6070096 Hayashi May 2000 A
6095982 Richards-Kortum et al. Aug 2000 A
6099466 Sano et al. Aug 2000 A
6110106 MacKinnon et al. Aug 2000 A
6120435 Eino Sep 2000 A
6148227 Wagnieres et al. Nov 2000 A
6161035 Furusawa Dec 2000 A
6181414 Raz et al. Jan 2001 B1
6192267 Scherninski et al. Feb 2001 B1
6212425 Irion et al. Apr 2001 B1
6226126 Conemac May 2001 B1
6258576 Richards-Kortum et al. Jul 2001 B1
6280378 Kazuhiro et al. Aug 2001 B1
6293911 Imaizumi et al. Sep 2001 B1
6315712 Rovegno Nov 2001 B1
6332092 Deckert et al. Dec 2001 B1
6364829 Fulghum Apr 2002 B1
6364831 Crowley Apr 2002 B1
6419628 Rudischhauser et al. Jul 2002 B1
6422994 Kaneko et al. Jul 2002 B1
6462770 Cline et al. Oct 2002 B1
6510338 Irion et al. Jan 2003 B1
6526213 Ilenda et al. Feb 2003 B1
6529239 Dyck et al. Mar 2003 B1
6529768 Hakamata Mar 2003 B1
6537211 Wang et al. Mar 2003 B1
6544102 Schafer et al. Apr 2003 B2
6571119 Hayashi May 2003 B2
6596996 Stone et al. Jul 2003 B1
6603552 Cline et al. Aug 2003 B1
6639664 Haan et al. Oct 2003 B2
6652452 Seifert et al. Nov 2003 B1
6750971 Overbeck et al. Jun 2004 B2
6772003 Kaneko et al. Aug 2004 B2
6773392 Kikuchi et al. Aug 2004 B2
6786865 Dhindsa Sep 2004 B2
6821245 Cline et al. Nov 2004 B2
6826424 Zeng et al. Nov 2004 B1
6898458 Zeng et al. May 2005 B2
6899675 Cline et al. May 2005 B2
6922583 Perelman et al. Jul 2005 B1
6960165 Ueno et al. Nov 2005 B2
7043291 Sendai May 2006 B2
7150552 Weidel Dec 2006 B2
7179222 Imaizumi et al. Feb 2007 B2
7235045 Wang et al. Jun 2007 B2
7236815 Richards-Kortum et al. Jun 2007 B2
7253894 Zeng et al. Aug 2007 B2
7324674 Ozawa et al. Jan 2008 B2
7333270 Pochapsky et al. Feb 2008 B1
7341557 Cline et al. Mar 2008 B2
7385772 Forkey et al. Jun 2008 B2
7420151 Fengler et al. Sep 2008 B2
7479990 Imaizumi et al. Jan 2009 B2
7697975 Zeng Apr 2010 B2
7704206 Suzuki et al. Apr 2010 B2
7722534 Cline et al. May 2010 B2
7798955 Ishihara et al. Sep 2010 B2
7811229 Sugimoto Oct 2010 B2
8140147 Maynard et al. Mar 2012 B2
8285015 Demos Oct 2012 B2
8337400 Mizuyoshi Dec 2012 B2
8408269 Fengler et al. Apr 2013 B2
8408772 Li Apr 2013 B2
8498695 Westwick et al. Jul 2013 B2
8630698 Fengler et al. Jan 2014 B2
8759243 Coffy et al. Jun 2014 B2
8773756 Tesar et al. Jul 2014 B2
8790253 Sunagawa et al. Jul 2014 B2
8961403 Cline et al. Feb 2015 B2
8979301 Moore Mar 2015 B2
9143746 Westwick et al. Sep 2015 B2
9173554 Fengler Nov 2015 B2
9295392 Douplik et al. Mar 2016 B2
9386909 Fengler et al. Jul 2016 B2
9435496 Moore Sep 2016 B2
20010016679 Futatsugi et al. Aug 2001 A1
20010028458 Xiao Oct 2001 A1
20020013937 Ostanevich et al. Jan 2002 A1
20020016533 Marchitto et al. Feb 2002 A1
20020021355 Utsui et al. Feb 2002 A1
20020035330 Cline et al. Mar 2002 A1
20020076480 Hsieh et al. Jun 2002 A1
20020138008 Tsujita et al. Sep 2002 A1
20020143243 Georgakoudi et al. Oct 2002 A1
20020155619 Kurihara et al. Oct 2002 A1
20020161282 Fulghum Oct 2002 A1
20020161283 Sendai Oct 2002 A1
20020161284 Tanaka Oct 2002 A1
20020175993 Ueno et al. Nov 2002 A1
20020177778 Averback et al. Nov 2002 A1
20020186478 Watanabe et al. Dec 2002 A1
20020196335 Ozawa Dec 2002 A1
20030002036 Haan et al. Jan 2003 A1
20030042493 Kazakevich Mar 2003 A1
20030117491 Avni et al. Jun 2003 A1
20030135092 Cline et al. Jul 2003 A1
20030153811 Muckner Aug 2003 A1
20030191368 Wang et al. Oct 2003 A1
20030229270 Suzuki et al. Dec 2003 A1
20040006276 Demos et al. Jan 2004 A1
20040010183 Dhindsa Jan 2004 A1
20040021859 Cunningham Feb 2004 A1
20040037454 Ozawa et al. Feb 2004 A1
20040044275 Hakamata Mar 2004 A1
20040046865 Ueno et al. Mar 2004 A1
20040133073 Berci et al. Jul 2004 A1
20040143162 Krattiger et al. Jul 2004 A1
20040148141 Tsujita et al. Jul 2004 A1
20040149998 Henson et al. Aug 2004 A1
20040156124 Okada Aug 2004 A1
20040186351 Imaizumi et al. Sep 2004 A1
20040218115 Kawana et al. Nov 2004 A1
20040225222 Zeng et al. Nov 2004 A1
20040245350 Zeng Dec 2004 A1
20040263643 Imaizumi et al. Dec 2004 A1
20050027166 Matsumoto et al. Feb 2005 A1
20050096505 Imaizumi et al. May 2005 A1
20050140270 Henson et al. Jun 2005 A1
20050143627 Cline et al. Jun 2005 A1
20050154319 Cline et al. Jul 2005 A1
20050171440 Maki et al. Aug 2005 A1
20050182291 Hirata Aug 2005 A1
20050182321 Frangioni Aug 2005 A1
20050203421 Zeng et al. Sep 2005 A1
20050256373 Bar-Or Nov 2005 A1
20050273011 Hattery et al. Dec 2005 A1
20050280783 Yamasaki et al. Dec 2005 A1
20050288593 Georgakoudi et al. Dec 2005 A1
20060002141 Ouderkirk et al. Jan 2006 A1
20060004292 Beylin Jan 2006 A1
20060017913 Kawamata et al. Jan 2006 A1
20060089554 Ishihara et al. Apr 2006 A1
20060146322 Komachi et al. Jul 2006 A1
20060149133 Sugimoto et al. Jul 2006 A1
20060155166 Takahashi et al. Jul 2006 A1
20060211915 Takeuchi et al. Sep 2006 A1
20060215406 Thrailkill Sep 2006 A1
20060217594 Ferguson Sep 2006 A1
20060241496 Fengler et al. Oct 2006 A1
20060258910 Stefanchik et al. Nov 2006 A1
20070041195 Chen Feb 2007 A1
20070091634 Sakurada Apr 2007 A1
20070177152 Tearney et al. Aug 2007 A1
20070213593 Nakaoka Sep 2007 A1
20070229309 Tomita et al. Oct 2007 A1
20080021274 Bayer et al. Jan 2008 A1
20080027280 Fengler et al. Jan 2008 A1
20080039697 Morishita Feb 2008 A1
20080074752 Chaves et al. Mar 2008 A1
20080177140 Cline et al. Jul 2008 A1
20080208006 Farr Aug 2008 A1
20080246920 Buczek et al. Oct 2008 A1
20090012361 MacKinnon et al. Jan 2009 A1
20090021739 Tsujita et al. Jan 2009 A1
20090040754 Brukilacchio et al. Feb 2009 A1
20090052185 Toriyama et al. Feb 2009 A1
20090114799 Maeda May 2009 A1
20090114803 Yamaguchi May 2009 A1
20090122135 Matsui May 2009 A1
20090122152 Yamaguchi et al. May 2009 A1
20090124854 Yamaguchi et al. May 2009 A1
20090153797 Allon et al. Jun 2009 A1
20090181339 Liang et al. Jul 2009 A1
20090201577 LaPlante et al. Aug 2009 A1
20090290149 Roth Nov 2009 A1
20100087741 Douplik et al. Apr 2010 A1
20100094136 Nakaoka et al. Apr 2010 A1
20100110168 Avni et al. May 2010 A1
20100110393 Chen et al. May 2010 A1
20100121146 Sugimoto May 2010 A1
20100125164 Labombard May 2010 A1
20100157039 Sugai Jun 2010 A1
20100168588 Matsumoto et al. Jul 2010 A1
20100198010 Cline et al. Aug 2010 A1
20100208487 Li Aug 2010 A1
20100277817 Durell Nov 2010 A1
20110270092 Kang et al. Nov 2011 A1
20120044462 Kaji Feb 2012 A1
20130237762 Fengler et al. Sep 2013 A1
20140194687 Fengler et al. Jul 2014 A1
20150184811 Moore Jul 2015 A1
20150230698 Cline et al. Aug 2015 A1
20160249019 Westwick et al. Aug 2016 A1
Foreign Referenced Citations (109)
Number Date Country
101726980 Jun 2010 CN
195 35 114 Mar 1996 DE
196 08 027 Sep 1996 DE
0 512 965 Nov 1992 EP
0 672 379 Sep 1995 EP
0 774 865 May 1997 EP
0 792 618 Sep 1997 EP
1 374 755 Jan 2004 EP
1 883 337 Feb 2008 EP
2 051 603 Apr 2009 EP
2 671 405 Jul 1992 FR
S-60-246733 Dec 1985 JP
S-61-159936 Jul 1986 JP
H-01-135349 May 1989 JP
02-049302 Feb 1990 JP
03-97439 Apr 1991 JP
03-97441 Apr 1991 JP
03-97442 Apr 1991 JP
05-115435 May 1993 JP
06-125911 May 1994 JP
H-07-155285 Jun 1995 JP
H-07-155286 Jun 1995 JP
H-07-155290 Jun 1995 JP
H-07-155291 Jun 1995 JP
H-07-155292 Jun 1995 JP
H-07-204156 Aug 1995 JP
H-07-222712 Aug 1995 JP
H-07-250804 Oct 1995 JP
H-07-250812 Oct 1995 JP
H-07-327913 Dec 1995 JP
H-08-126605 May 1996 JP
08-140928 Jun 1996 JP
08-140929 Jun 1996 JP
H-08-224208 Sep 1996 JP
H-08-224209 Sep 1996 JP
H-08-224210 Sep 1996 JP
H-08-224240 Sep 1996 JP
H-08-252218 Oct 1996 JP
09-066023 Mar 1997 JP
09-070384 Mar 1997 JP
H-10-127563 May 1998 JP
H-10-151104 Jun 1998 JP
10-225427 Aug 1998 JP
H-10-201700 Aug 1998 JP
H10-201707 Aug 1998 JP
H-10-225426 Aug 1998 JP
H-10-243915 Sep 1998 JP
H-10-243920 Sep 1998 JP
H-10-308114 Nov 1998 JP
H-10-309281 Nov 1998 JP
H-10-309282 Nov 1998 JP
H10-321005 Dec 1998 JP
H-10-328129 Dec 1998 JP
11-047079 Feb 1999 JP
11-089789 Apr 1999 JP
H-11-104059 Apr 1999 JP
H-11-104060 Apr 1999 JP
H-11-104061 Apr 1999 JP
H-11-104070 Apr 1999 JP
H-11-113839 Apr 1999 JP
H-11-155812 Jun 1999 JP
H-11-244220 Sep 1999 JP
H-11-332819 Dec 1999 JP
2000-504968 Apr 2000 JP
2000-245693 Sep 2000 JP
2000-354583 Dec 2000 JP
2002-000560 Jan 2002 JP
2002-244122 Aug 2002 JP
2003-045210 Feb 2003 JP
2004-024611 Jan 2004 JP
2004-094043 Mar 2004 JP
2004-163902 Jun 2004 JP
2004-520105 Jul 2004 JP
2004-247156 Sep 2004 JP
2004-289545 Oct 2004 JP
2004-292722 Oct 2004 JP
2005-010315 Jan 2005 JP
2005-058618 Mar 2005 JP
2005-058619 Mar 2005 JP
2005-058620 Mar 2005 JP
2005-080819 Mar 2005 JP
2005-081079 Mar 2005 JP
2005-292404 Oct 2005 JP
2006-087764 Apr 2006 JP
2006-525494 Nov 2006 JP
2007029453 Feb 2007 JP
2007-072392 Mar 2007 JP
2007089840 Apr 2007 JP
2010-117442 May 2010 JP
2011-500921 Jan 2011 JP
2011528918 Dec 2011 JP
5231625 Mar 2013 JP
5859578 Feb 2016 JP
99592 Nov 2010 RU
WO-9304648 Mar 1993 WO
WO-9413191 Jun 1994 WO
WO-9526673 Oct 1995 WO
WO-9824360 Jun 1998 WO
WO-9901749 Jan 1999 WO
WO-9953832 Oct 1999 WO
WO-0042910 Jul 2000 WO
WO-0054652 Sep 2000 WO
WO-0207587 Jan 2002 WO
WO-0250518 Jun 2002 WO
WO-03059159 Jul 2003 WO
WO-03059159 Jul 2003 WO
WO-2006116847 Nov 2006 WO
WO-2008011722 Jan 2008 WO
WO-2009033021 Mar 2009 WO
Non-Patent Literature Citations (94)
Entry
US 6,692,429, 02/2004, Imaizumi et al. (withdrawn)
U.S.P.T.O., Final Rejection for U.S. Appl. No. 12/933,512 (Apr. 24, 2015).
U.S.P.T.O., Non-Final Rejection for U.S. Appl. No. 12/933,512 (Jul. 2, 2013).
Apr. 3, 2015 Office Action issued in Japanese Application No. 2013-058356.
Sep. 21, 2010 International Preliminary Report on Patentability issued in International Application No. PCT/US2009/037506.
Apr. 20, 2012 Office Action issued in Japanese Patent Application No. 2011-500921.
May 26, 2014 Office Action issued in Japanese Patent Application No. 2013-058356.
Alfano, R.R. et al. (1987). “Fluorescence Spectra From Cancerous and Normal Human Breast and Lung Tissues,” IEEE Journal of Quantum Electronics QE-23(10):1806-1811.
Andersson-Engels, S. et al. (1989). “Tissue Diagnostics Using Laser Induced Fluorescence,” Ber. Bunsenges Physical Chemistry 93:335-342.
Bhunchet, E. et al. (2002). “Fluorescein Electronic Endoscopy: A Novel Method for Detection of Early Stage Gastric Cancer Not Evident to Routine Endoscopy,” Gastrointestinal Endoscopy 55(4):562-571.
Hung, J. et al. (1991). “Autofluorescence of Normal and Malignant Bronchial Tissue,” Lasers in Surgery and Medicine 11:99-105.
Torok et al. (1996). “Simultaneous Digital ICG and Fluorescein Angiography,” Klin Monatsbl Augenheikld 208:333-336.
European Office Action mailed on Nov. 19, 2015, for EP Application No. 07 785 001.4 filed on Jul. 30, 2007, four pages.
Extended European Search Report mailed on Jan. 24, 2012 for EP Application No. 07 785 001.4 filed on Jul. 30, 2007, seven pages.
Supplemental European Search Report mailed on Jan. 24, 2012, for European Patent Application No. 07785001.4 filed on Jul. 30, 2007, six pages.
Supplemental European Search Report mailed on Oct. 9, 2013, for European Patent Application No. 06721854.5 filed on May 4, 2005, six pages.
European Office Action mailed Dec. 3, 2015, for EP Application No. 08706262.6 filed on Jan. 23, 2008; fifteen pages.
European Extended Search Report dated Sep. 20, 2013, for EP Application No. 08706262.6 filed on Jan. 23, 2008, five pages.
European Office Action mailed Sep. 29, 2015, for EP Application No. 09721252.6 filed Mar. 18, 2009; five pages.
European Extended Search Report dated Jul. 17, 2014, for EP Application No. 09721252.6 filed Mar. 18, 2009; eleven pages.
International Preliminary Report on Patentability mailed on Nov. 6, 2007, for International Application No. PCT/CA2006/000669, nine pages.
International Preliminary Report on Patentability mailed on Feb. 3, 2009, for International Application No. PCT/CA2007/001335, five pages.
International Search Report mailed on Aug. 3, 2006, for International Application No. PCT/CA2006/000669, three pages.
International Search Report mailed on Dec. 7, 2007, for International Application No. PCT/CA2007/001335, two pages.
International Search Report mailed on Jan. 21, 2002, for International Application No. PCT/US2001/022198 filed on Jul. 13, 2001, three pages.
International Search Report from International Application No. PCT/CA2008/000115 dated May 13, 2008; one page.
International Search Report mailed Jul. 22, 2009, for International Application No. PCT/US09/37506; two pages.
Japanese Office Action mailed on Nov. 11, 2011, for Japanese Patent Application No. 2009-521077, filed on Jul. 30, 2007, four pages.
Japanese Office Action mailed on Feb. 17, 2012, for Japanese Patent Application No. 2008-509275, filed on Apr. 27, 2006, six pages.
Japanese Office Action mailed on Sep. 14, 2012, for Japanese Patent Application No. 2008-509275, filed on Apr. 27, 2006, seven pages.
Japanese Final Office Action mailed on Aug. 2, 2013, for Japanese Patent Application No. 2008-509275, filed on Apr. 27, 2006, four pages.
Japanese Office Action mailed on Sep. 19, 2014, for Japanese Patent Application No. 2013-246636, filed on Apr. 27, 2006, six pages.
Japanese Office dated Dec. 26, 2012, issued in counterpart Japanese Application No. 2011-500921.
Written Opinion of the International Searching Authority mailed on Aug. 3, 2006, for International Application No. PCT/CA2006/000669, eight pages.
Written Opinion of the International Searching Authority mailed on Dec. 7, 2007, for International Application No. PCT/CA2007/001335, four pages.
Non-Final Office Action with Restriction Requirement mailed on Mar. 4, 2011, for U.S. Appl. No. 11/830,323, nine pages.
Non-Final Office Action mailed on Jun. 9, 2011, for U.S. Appl. No. 11/830,323, five pages.
Notice of Allowance mailed on Sep. 14, 2012, for U.S. Appl. No. 11/830,323, eight pages.
Notice of Allowance mailed on Aug. 6, 2015, for U.S. Appl. No. 13/853,656, seven pages.
Notice of Allowance mailed on Nov. 23, 2015, for U.S. Appl. No. 13/853,656, seven pages.
Notice of Allowance mailed on Mar. 28, 2016, for U.S. Appl. No. 13/853,656, eight pages.
Non-Final Office Action mailed on May 18, 2004, for U.S. Appl. No. 10/050,601, eight pages.
Supplemental Notice of Allowability mailed on Mar. 10, 2005, for U.S. Appl. No. 10/050,601, five pages.
Notice of Allowance mailed on Aug. 26, 2004, for U.S. Appl. No. 10/050,601, eight pages.
Non-Final Office Action mailed on Apr. 2, 2009, for U.S. Appl. No. 11/009,965, thirteen pages.
Final Office Action mailed on Nov. 24, 2009, for U.S. Appl. No. 11/009,965, fourteen pages.
Non-Final Office Action mailed on Jun. 23, 2010, for U.S. Appl. No. 11/009,965, fifteen pages.
Non-Final Office Action mailed on Sep. 12, 2014, for U.S. Appl. No. 14/154,177, four pages.
Final Office Action mailed on Jun. 18, 2015, for U.S. Appl. No. 14/154,177, eight pages.
Non-Final Office Action mailed on Jun. 20, 2008, for U.S. Appl. No. 11/009,398, fifteen pages.
Non-Final Office Action mailed on Jan. 2, 2008, for U.S. Appl. No. 11/122,267, five pages.
Final Office Action mailed on Jul. 23, 2008, for U.S. Appl. No. 11/122,267, six pages.
Non-Final Office Action mailed on Dec. 10, 2010, for U.S. Appl. No. 11/412,715, ten pages.
Final Office Action mailed on May 11, 2011, for U.S. Appl. No. 11/412,715, eight pages.
Non-Final Office Action mailed on Dec. 14, 2011, for U.S. Appl. No. 11/412,715, eight pages.
Notice of Allowance mailed on Sep. 10, 2013, for U.S. Appl. No. 11/412,715, eight pages.
Non-Final Office Action mailed on Jan. 20, 2016, for U.S. Appl. No. 14/629,473, fifteen pages.
Non-Final Office Action mailed on Jun. 1, 2007, for U.S. Appl. No. 10/899,648, seven pages.
Notice of Allowance mailed on Oct. 5, 2007, for U.S. Appl. No. 10/899,648, six pages.
Notice of Allowance mailed on Jan. 2, 2008, for U.S. Appl. No. 10/899,648, three pages.
Non-Final Office Action mailed on Nov. 23, 2009, for U.S. Appl. No. 11/969,974, seven pages.
Notice of Allowance mailed on Feb. 25, 2010, for U.S. Appl. No. 11/969,974, four pages.
Non-Final Office Action mailed on Aug. 16, 2013, for U.S. Appl. No. 12/761,462, ten pages.
Final Office Action mailed on Jun. 5, 2014, for U.S. Appl. No. 12/761,462, fourteen pages.
Notice of Allowance mailed on Oct. 10, 2014, for U.S. Appl. No. 12/761,462, ten pages.
Non-Final Office Action mailed on Aug. 16, 2013, for U.S. Appl. No. 12/761,523, nine pages.
Non-Final Office Action mailed on Jul. 17, 2003, for U.S. Appl. No. 09/905,642, six pages.
Notice of Allowance mailed on Apr. 7, 2004, for U.S. Appl. No. 09/905,642, six pages.
Non-Final Office Action mailed Oct. 7, 2011, for U.S. Appl. No. 11/964,330; ten pages.
Final Office Action mailed May 21, 2012, for U.S. Appl. No. 11/964,330; twelve pages.
Notice of Allowance mailed Dec. 10, 2012, for U.S. Appl. No. 11/964,330; seven pages.
Notice of Allowance mailed Mar. 22, 2013, for U.S. Appl. No. 11/964,330; eight pages.
Non-Final Office Action mailed Nov. 5, 2014, for U.S. Appl. No. 13/930,225; six pages.
Notice of Allowance mailed May 18, 2015, for U.S. Appl. No. 13/930,225; nine pages.
Non-Final Office Action mailed Feb. 3, 2010, for U.S. Appl. No. 11/626,308; eleven pages.
Notice of Allowance mailed Jun. 25, 2015, for U.S. Appl. No. 12/933,512 filed Nov. 24, 2010; fourteen pages.
Dawson, J.B. et al. (Jul. 1980). “A Theoretical and Experimental Study of Light Absorption and Scattering by in Vivo Skin,” Phys. Med. Biol. 25(4):695-709.
Georgakoudi, I et al. (2003). “Quantitative Characterization of Biological Tissue Using Optical Spectroscopy,” in Chapter 31 of Biomedical Photonics Handbook, Tuan Vo-Dinh (ed.), CRC Press, New York, thirty three pages.
Georgakoudi, I et al. (Apr. 2005). “Characterization of Dysplastic Tissue Morphology and Biochemistry in Barrett's Esophagus using Diffuse Reflectance and Light Scattering Spectroscopy,” Techniques in Gastrointestinal Endoscopy 7(2):100-105.
Chinese Office action mailed on Jul. 29, 2016 for application No. 2012800222843 filed on Mar. 8, 2012, eight pages.
Chinese Office action mailed on Nov. 24, 2015 for application No. 2012800222843 filed on Mar. 8, 2012, sixteen pages.
European Office Action mailed on Nov. 3, 2015 for EP Patent Application No. 12754208.2 filed Oct. 4, 2013, four pages.
European Supplemental Search Report mailed on Oct. 1, 2014 for EP Application No. 12754208.2 filed on Mar. 8, 2012, five pages.
International Search Report mailed on Aug. 3, 2012, for International Application No. PCT/IB2012/000601, filed on Mar. 8, 2012, three pages.
Japanese Notice of Allowance mailed on Nov. 28, 2016 for Japanese Patent Application No. 2015-245598, filed on Mar. 8, 2012, six pages.
Japanese Office Action mailed on Jul. 22, 2014 for Japanese Patent Application No. 2013-557187 filed Mar. 8, 2012, seven pages.
Japanese Office Action mailed on Mar. 9, 2015 for Japanese Patent Application No. 2013-557187, filed Mar. 8, 2012, five pages.
Korean Decision of Refusal Action mailed on Aug. 30, 2016 for patent application No. 10-2015-7033310 filed on Mar. 8, 2012, seven pages.
Korean Office Action mailed on Aug. 20, 2015 for patent application No. 20137026479 filed on Mar. 8, 2012.
Korean Office Action mailed on Dec. 8, 2015 for patent application No. 20157033310 filed on Mar. 8, 2012, seven pages.
Non Final Office Action mailed on Jun. 27, 2014 for U.S. Appl. No. 13/415,561, filed on Mar. 3, 2012, fourteen pages.
Non Final Office Action mailed on Oct. 23, 2013 for U.S. Appl. No. 13/415,561, filed on Mar. 8, 2012, ten pages.
Non Final Office Action mailed on Oct. 5, 2016 for U.S. Appl. No. 15/247,419, filed on Aug. 25, 2016, eight pages.
Russian Office Action—Decision to Grant mailed on Aug. 19, 2016 for Russian Patent Application No. 2013144845/07, filed on Mar. 8, 2012, thirteen pages.
Related Publications (1)
Number Date Country
20160100763 A1 Apr 2016 US
Provisional Applications (1)
Number Date Country
61037514 Mar 2008 US
Continuations (1)
Number Date Country
Parent 12933512 US
Child 14873842 US