Dual mode real-time screening and rapid full-area, selective-spectral, remote imaging and analysis device and process

• US 6,678,398 B2
• Filed: 03/12/2003
• Issued: 01/13/2004
• Est. Priority Date: 09/18/2000
• Status: Expired due to Fees

• Current Assignee: STI Medical Systems LLC
• Original Assignee: STI Medical Systems LLC
• Inventors: Wolters, Rolf Holger, Walton, David George Shibasaki, Sweat, Joseph Allen, Deweert, Michael James, Seiple, Robert Benton Jr.
• Primary Examiner(s): Patel, Jayanti K.
• Assistant Examiner(s): AZARIAN, SEYED H
• Application Number:
  US10/387,761
• Publication Number:
  US 20030158470A1
• Time in Patent Office: 307 Days
• Field of Search: 382/128, 382/129, 382/130, 382/131, 382/132, 382/133, 382/134, 356/456, 348/65, 600/300, 600/313, 600/321, 600/342, 600/420, 600/424, 600/425, 600/442, 600/451
• US Class Current: 382/128
• CPC Class Codes: A61B 1/00186 with imaging filters
• CPC Class Codes: A61B 1/043 for fluorescence imaging
• CPC Class Codes: A61B 1/0638 providing two or more wavelengths
• CPC Class Codes: A61B 1/0653 with wavelength conversion
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence

Abstract

The invention provides a device and process for real-time screening of areas that can be identified as suspicious either through image segmentation utilizing image processing techniques or through treatment with an exogenous fluorescent marker that selectively localizes in abnormal areas. If screening detects a suspicious area, then the invention allows acquiring of autofluorescence images at multiple selected narrow differentiating spectral bands so that a “virtual biopsy” can be obtained to differentiate abnormal areas from normal areas based on differentiating portions of autofluorescence spectra. Full spatial information is collected, but autofluorescence data is collected only at the selected narrow spectral bands, avoiding the collection of full spectral data, so that the speed of analysis is increased.

Claims

1. A dual mode device for real-time screening and rapid full-area, selective-spectral, remote imaging and analysis to differentiate normal tissues having a normal fluorescence spectrum from abnormal tissues having an abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at differentiating portions when said tissues are excited by an excitation light, wherein said abnormal tissues emit fluorescent light at a marker wavelength when said tissues are treated with an exogenous fluorescent marker that selectively localizes in said abnormal tissue and when said tissues are excited by said excitation light, comprising:

an imaging light source emitting imaging light;

a closable shutter to selectively block said imaging light during an analysis mode;

a marker filter spaced apart from said imaging light that filters light of said marker wavelength from said imaging light to create markerless imaging light;

an excitation light source emitting excitation light;

an optical combiner combining said markerless imaging light and said excitation light;

an illumination light guide that guides said markerless imaging light and said excitation light to illuminate said tissues;

whereby, when said shutter is opened, said device is in a screening mode and said tissues are illuminated with both markerless imaging light and said excitation light and said tissues reflect said markerless imaging light to form reflected light and whereby said abnormal tissues fluoresce at said marker wavelength to form fluorescent light;

whereby, when said shutter is closed, said device is in said analysis mode and said tissues are illuminated only with said excitation light and said normal tissues fluoresce with said normal fluorescence spectrum and said abnormal tissues fluoresce with said abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at said differentiating portions;

a high resolution imager to provide full area images of said tissues;

a sensitive imager to provide full area images of said tissues; and

an adjustable narrow band filter interposed between said tissues and said imagers that;

in said screening mode, separates and directs said fluorescent light with said marker wavelength to said sensitive imager to form a marker image, and that separates and directs said reflected light to said high resolution imager to form an imaging image;

in said analysis mode, deflects multiple selected narrow bands of said differentiating portions to said sensitive imager to form multiple full area selective-spectral images, whereby collecting full spectral information is avoided;

an image processor operably connected to said imagers that combines and processes data from said imagers approximately in real time that;

in said screening mode, allows comparison between said marker image and said imaging image by a method selected from the group consisting of a false color overlay of said marker image over said imaging image, displaying said marker image side by side with said imaging image, and alternately displaying said marker image and said imaging image; and

in said analysis mode, analyzes said multiple full area selective-spectral images and differentiates said normal tissue from said abnormal tissues.

10. A device according to any one of claims 1 to 6, 8 or 9, wherein at least one of said narrow bands of said differentiating portions is at most approximately 10 nm wide.

11. A device according to any one of claims 1, 2, 6, 8 or 9, wherein said image processor analyzes said multiple selective-spectral images and differentiates said normal tissue from said abnormal tissue using a process selected from the group consisting of comparing ratios of spectral peaks at selected spectral bands, principal component analysis, minimum noise fraction, wavelet analysis, band ratio test and fractal pattern recognition.

12. A device according to claim 11, wherein said illumination light guide has ultraviolet transmissivity of at least 80%.

13. A device according to claim 11, wherein said illumination light guide has ultraviolet transmissivity of approximately 95% of ultraviolet light between approximately 330 nm and approximately 400 nm.

2. A dual mode device for real-time screening and rapid full-area, selective-spectral, remote imaging and analysis to differentiate normal tissues having a normal fluorescence spectrum from abnormal tissues having an abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at differentiating portions when said tissues are excited by an excitation light, comprising:

an activatable imaging light source emitting imaging light during a screening mode;

an activatable excitation light source emitting excitation light during an analysis mode;

an illumination light guide that guides said imaging light and said excitation light to illuminate said tissues;

whereby, when said imaging light is activated, said excitation light is deactivated, said device is in a screening mode and said tissues are illuminated with said imaging light that reflects from said tissues to form reflected light;

whereby, when said excitation light is activated, said imaging light is deactivated, said device is in said analysis mode and said tissues are illuminated only with said excitation light and said normal tissues fluoresce with a normal fluorescence spectrum and said abnormal tissues fluoresce with said abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at said differentiating portions;

a high resolution imager to form full area images of said tissues;

a sensitive imager to form full area images of said tissues; and

an adjustable narrow band filter interposed between said tissues and said imagers that;

in said screening mode, separates and directs said reflected light to one of said imagers to form a screening image;

in said analysis mode, deflects multiple selected narrow bands of said differentiating portions to said sensitive imager to form multiple full area selective-spectral images, whereby collecting full spectral information is avoided;

an image processor operably connected to said imagers that, in approximately real time;

in said screening mode, performs a pre-segmentation analysis to segment said screening image into suspicious areas; and

in said analysis mode, analyzes said multiple full area selective-spectral images and differentiates said normal tissue from said abnormal tissue.

7. A device according any one of claims 2 to 6, wherein at least one of said activatable light sources is selected from the group consisting of temperature stabilized LEDs with power cycled on during said screening mode and a light sources with activatable shutters opened during applicable modes.

3. A device for area imaging and spectroscopically distinguishing normal tissues having a normal fluorescence spectrum from abnormal tissues having an abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at differentiating portions when said tissues are excited by an excitation light, wherein said abnormal tissues fluoresce differently from said normal tissues at a marker wavelength when said tissues are treated with an exogenous fluorescent marker that selectively localizes in said abnormal tissue and when said tissues are excited by said excitation light, comprising:

an activatable imaging light source activatably emitting imaging light when in a screening mode;

an excitation light source emitting excitation light in both said screening mode and an analysis mode, wherein said excitation light is selected from the group consisting of blue light, violet light and ultraviolet light;

an optical combiner that combines said imaging light and said excitation light;

a narrow band filter that removes light at said marker wavelength from said imaging light, resulting in markerless imaging light;

an illuminating light guide that directs said markerless imaging light and said excitation light onto said tissues,

whereby in said screening mode said tissues are illuminated with said markerless imaging light and said excitation light, said tissues reflect said markerless imaging light to form reflected light, and said abnormal tissues fluoresce at said marker wavelength, and

whereby in said analysis mode said tissues are illuminated only with said excitation light, and said abnormal tissues fluoresce differently from said normal tissues at said differentiating portions;

an imaging bundle positioned to transmit images of said tissues as so illuminated;

a monochromatic CCD;

a high resolution color CCD;

an adjustable narrow band filter operably connected to said imaging bundle that;

in said screening mode, directs light from said tissues at said marker wavelength to said monochromatic CCD to form a marker image and directs said reflected light from said tissues to said color CCD to form an reflected light image; and

in said analysis mode, directs said multiple narrow bands of said differentiating portions to said monochromatic CCD, whereby collecting full spectral information is avoided;

an image processor operably connected to said CCDs that combines data from said CCDs in approximately real time that;

in said screening mode displays and compares said marker image from said monochromatic CCD and said reflected light image from said color CCD using a method selected from the group consisting of a false color overlay of said marker image over said reflected light image, displaying said marker image next to said reflected light image, and alternately displaying said maker image and said reflected light image;

in an analysis mode, analyzes said multiple narrow bands of differentiating portions and differentiates said normal tissue from said abnormal tissue to form a differentiated image and displays and compares said differentiated image and said reflected light image using a method selected from the group consisting of a false color overlay of said differentiated image over said reflected light image, displaying said differentiated image next to said reflected light image, and alternately displaying said reflected light image and said differentiated image.

4. A device for area imaging and spectroscopically distinguishing normal tissues having a normal fluorescence spectrum from abnormal tissues having an abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at differentiating portions when said tissues are excited by a an autofluorescence excitation light, wherein said abnormal tissues fluoresce differently from said normal tissues at a marker wavelength when said tissues are treated with an exogenous fluorescent marker that selectively localizes in said abnormal tissue and when said tissues are excited by a marker excitation light, comprising:

an activatable imaging light source activatably emitting imaging light when in a screening mode;

an activatable marker excitation light source activatably emitting marker excitation light when in said screening mode;

an activatable autofluorescence excitation light source emitting autofluorescence excitation light when in an analysis mode, wherein said autofluorescence excitation light is selected from the group consisting of blue light, violet light and ultraviolet light;

a dichroic mirror that combines said imaging light and said marker excitation light when in said screening mode;

a narrow band filter that removes light at said marker wavelength from said imaging light, resulting in markerless imaging light;

an illuminating light guide that directs said markerless imaging light and said marker excitation light onto said tissues when in said screening mode, and that directs said autofluorescence excitation light onto said tissues when in said analysis mode,

whereby in said screening mode said tissues are illuminated with said markerless imaging light and said marker excitation light, said tissues reflect said markerless imaging light to form reflected light, and said abnormal tissues fluoresce at said marker wavelength, and

whereby in said analysis mode said tissues are illuminated only with said autofluorescence excitation light, and said abnormal tissues fluoresce differently from said normal tissues at said differentiating portions;

an imaging bundle positioned to receive and transmit light from said tissues as so illuminated;

a monochromatic CCD;

a high resolution color CCD;

an adjustable narrow band filter operably connected to said imaging bundle that;

in said screening mode, directs light from said tissues at said marker wavelength to said monochromatic CCD to form a marker image and directs said reflected light from said tissues to said color CCD to form a reflected light image; and

in said analysis mode, directs said multiple narrow bands of said differentiating portions to said monochromatic CCD, whereby collecting full spectral information is avoided;

an image processor operably connected to said CCDs that processes data from said CCDs in approximately real time that;

in said screening mode displays and compares said marker image from said monochromatic CCD and said reflected light image from said color CCD using a method selected from the group consisting of a false color overlay of said marker image over said reflected light image, displaying said marker image next to said reflected light image, and alternately displaying said marker image and said reflected light image;

in an analysis mode, analyzes said multiple narrow bands of differentiating portions and differentiates said normal tissue from said abnormal tissue to form a differentiated image and displays and compares said differentiated image and said reflected light image using a method selected from the group consisting of a false color overlay of said differentiated image over said reflected light image, displaying said differentiated image next to said reflected light image, and alternately displaying said differentiated image and said reflected light image.

5. A device for area imaging and spectroscopically distinguishing normal tissues having a normal fluorescence spectrum from abnormal tissues having an abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at differentiating portions when said tissues are excited by a an autofluorescence excitation light, wherein said abnormal tissues fluoresce differently from said normal tissues at a marker wavelength when said tissues are treated with an exogenous fluorescent marker that selectively localizes in said abnormal tissue and when said tissues are excited by a marker excitation light, comprising:

an activatable visible light source activatably emitting visible light when in a screening mode;

an activatable marker excitation light source activatably emitting marker excitation light when in said screening mode;

an autofluorescence excitation light source emitting autofluorescence excitation light when in an analysis mode, wherein said autofluorescence excitation light is selected from the group consisting of blue light, violet light and ultraviolet light;

a dichroic mirror that combines said imaging light and said marker excitation light when in said screening mode;

a narrow band filter that removes light at said marker wavelength from said imaging light, resulting in markerless imaging light;

a fiber optic illumination bundle having ultraviolet transmissivity of at least 80% that directs said markerless imaging light and said marker excitation light onto said tissues when in said screening mode, and that directs said autofluorescence excitation light onto said tissues when in said analysis mode,

whereby in said screening mode said tissues are illuminated with said markerless imaging light and said marker excitation light, said tissues reflect said markerless imaging light to form reflected light, and said abnormal tissues fluoresce at said marker wavelength, and

whereby in said analysis mode said tissues are illuminated only with said autofluorescence excitation light, and said abnormal tissues fluoresce differently from said normal tissues at said differentiating portions;

a fiber optic imaging bundle positioned to receive and transmit light from said tissues as so illuminated;

a monochromatic CCD;

a high resolution color CCD;

an adjustable narrow band filter selected from the group consisting of an acousto-optical tunable filter, a liquid crystal tunable filter and a filter wheel operably connected to said imaging bundle that;

in said screening mode, directs light from said tissues at said marker wavelength to said monochromatic CCD to form a marker image and directs said reflected light from said tissues to said color CCD to form a reflected light image; and

in said analysis mode, directs approximately 4 to approximately 9 narrow spectral bands selected from said differentiating portions to said monochromatic CCD, whereby collecting full spectral information is avoided;

an image processor operably connected to said CCDs that processes data from said CCDs in approximately real time that;

in said screening mode displays and compares said marker image from said monochromatic CCD and said reflected light image from said color CCD using a method selected from the group consisting of a false color overlay of said marker image over said reflected light image, displaying said marker image next to said reflected light image and alternately displaying said marker image and said reflected light image;

in an analysis mode, analyzes said 4 to 9 narrow spectral bands and differentiates said normal tissue from said abnormal tissue to form a differentiated image and displays and compares said differentiated image and said reflected light image using a method selected from the group consisting of a false color overlay of said differentiated image over said reflected light image, displaying said differentiated image next to said reflected light image, and alternately displaying said differentiated image and said reflected light image.

6. A dual mode device for real-time screening and rapid full-area, selective-spectral, remote imaging and analysis to differentiate normal tissues having a normal fluorescence spectrum from abnormal tissues having an abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at differentiating portions when said tissues are excited by an excitation light, comprising:

an activatable imaging light source emitting imaging light;

a closable shutter to selectively block said imaging light during an analysis mode;

an activatable excitation light source emitting excitation light;

an illumination light guide that guides said imaging light and said excitation light to illuminate said tissues;

whereby, when said shutter is opened, said device is in a screening mode and said tissues are illuminated at least with said imaging light and said tissues reflect said imaging light to form reflected light;

whereby, when said shutter is closed, said device is in said analysis mode and said tissues are illuminated with said excitation light and said normal tissues fluoresce with a normal fluorescence spectrum and said abnormal tissues fluoresce with said abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at said differentiating portions;

a high resolution imager to image said tissues;

a sensitive imager to image said tissues; and

an adjustable narrow band filter interposed between said tissues and said imagers that;

in said screening mode, directs said reflected light to said high resolution imager to form an imaging image;

in said analysis mode, deflects multiple selected narrow bands of said differentiating portions to said sensitive imager to form multiple selective-spectral images, whereby collecting full spectral information is avoided;

an image processor operably connected to said imagers that combines data from said imagers approximately in real time that;

in said analysis mode, analyzes said multiple selective-spectral images and differentiates said normal tissue from said abnormal tissue using a process selected from the group consisting of comparing ratios of spectral peaks at selected spectral bands, principal component analysis, minimum noise fraction, wavelet analysis, band ratio test and fractal pattern recognition;

whereby screening for said abnormal tissue can be performed during said screening mode by a method selected from the group consisting of conventional visual inspection or pre-segmentation analysis of said imaging image.

8. A dual mode device for real-time screening and rapid full-area, selective-spectral, remote imaging and analysis to differentiate normal tissues having a normal fluorescence spectrum from abnormal tissues having an abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at differentiating portions when said tissues are excited by an excitation light, comprising:

an excitation light source emitting excitation light during an analysis mode;

an illumination light guide that guides said excitation light to illuminate said tissues with said excitation light during said analysis mode;

whereby, when said tissues are illuminated with said excitation light, said normal tissues fluoresce with said normal fluorescence spectrum and said abnormal tissues fluoresce with said abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at said differentiating portions;

a sensitive imager to provide full area images of said tissues; and

an adjustable narrow band filter interposed between said tissues and said sensitive imager that, in said analysis mode, deflects multiple selected narrow bands of said differentiating portions to said imager to form multiple full area selective-spectral images, whereby collecting full spectral information is avoided; and

an image processor operably connected to said imager that combines and processes data from said imager that, in said analysis mode, rapidly analyzes said multiple full area selective-spectral images to differentiate said normal tissue from said abnormal tissues, whereby a virtual biopsy of said tissues is performed.

9. A dual mode device for real-time screening and rapid full-area, selective-spectral, remote imaging and analysis to differentiate normal tissues having a normal fluorescence spectrum from abnormal tissues having an abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at differentiating portions when said tissues are excited by an excitation light, wherein said abnormal tissues emit fluorescent light at a marker wavelength when said tissues are treated with an exogenous fluorescent marker that selectively localizes in said abnormal tissue and when said tissues are excited by said excitation light, comprising:

an imaging light source emitting markerless imaging light free of light of said marker wavelength during a screening mode;

an excitation light source emitting excitation light during said screening mode and during an analysis mode;

combining means for combining said markerless imaging light and said excitation light during said screening mode;

an illumination light guide that guides said markerless imaging light and said excitation light to illuminate said tissues;

whereby, when said device is in said screening mode, said tissues are illuminated with both said markerless imaging light and said excitation light and said tissues reflect said markerless imaging light to form reflected light and said abnormal tissues fluoresce at said marker wavelength to form fluorescent light;

whereby, when said device is in said analysis mode, said tissues are illuminated only with said excitation light, said normal tissues fluoresce with said normal fluorescence spectrum and said abnormal tissues fluoresce with said abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at said differentiating portions;

a high resolution imager to provide full area images of said tissues;

a sensitive imager to provide full area images of said tissues; and

an adjustable narrow band filter interposed between said tissues and said imagers that;

in said screening mode, separates and directs said fluorescent light with said marker wavelength to said sensitive imager to form a marker image, and that separates and directs said reflected light to said high resolution imager to form an imaging image;

in said analysis mode, deflects multiple selected narrow bands of said differentiating portions to said sensitive imager to form multiple full area selective-spectral images, whereby collecting full spectral information is avoided;

an image processor operably connected to said imagers that combines and processes data from said imagers that;

in said screening mode, approximately in real time, allows comparison between said marker image and said imaging image by a method selected from the group consisting of a false color overlay of said marker image over said imaging image, displaying said marker image side by side with said imaging image, and alternately displaying said marker image and said imaging image; and

in said analysis mode, rapidly analyzes said multiple full area selective-spectral images to differentiate said normal tissue from said abnormal tissues.

14. A process for real-time screening and rapid full-area, selective-spectral, remote imaging and analysis to differentiate normal tissues having a normal fluorescence spectrum from abnormal tissues having an abnormal fluorescence spectrum that differs from said normal fluorescence spectrum at differentiating portions when said tissues are excited by an excitation light, wherein said abnormal tissues emit fluorescent light at a marker wavelength when said tissues are treated with an exogenous fluorescent marker that selectively localizes in said abnormal tissue and when said tissues are excited by said excitation light, comprising:

administering said exogenous fluorescent marker to said tissues;

(a) in a screening mode;

illuminating said tissues with said excitation light and with visible light free from light having said marker wavelength, whereby said tissues reflect said visible light to form reflected visible light and whereby said abnormal tissues emit marker fluorescent light at said marker wavelength;

separating said reflected visible light and said marker fluorescent light;

displaying an imaging image of said tissues from said reflected visible light;

displaying a marker image of said tissues from said marker fluorescent light;

(b) in an analysis mode;

illuminating said tissues with said excitation light, whereby said abnormal tissues fluoresce differently from said normal tissues at said differentiating portions;

selecting light in multiple spectral bands within said differentiating portions to form selective-spectral images, whereby collecting full spectral information is avoided;

processing said selective-spectral images to differentiate said normal tissue from said abnormal tissue using a method selected from the group consisting of comparing ratios of spectral peaks at selected spectral bands, principal component analysis, minimum noise fraction, wavelet analysis, band ratio test and fractal pattern recognition.

15. A process according to claim 14 wherein at least one of said bands of said differentiating portions is at most approximately 10 nm wide.