Digitally enhanced microscopy for multiplexed histology

Patent metadata

Field	Value
Publication number	US-10778913-B2
Application number	US-201314027093-A
Country	US
Kind code	B2
Filing date	Sep 13, 2013
Priority date	Mar 12, 2013
Publication date	Sep 15, 2020
Grant date	Sep 15, 2020

Abstract

An imaging system that can include a microscope for directly viewing a biological specimen and a multi-spectral imaging apparatus for outputting digitally enhanced images, near-video rate imaging, and/or videos of the specimen. An imaging system that can include a digital scanner that digitally processes images to produce a composite image with enhanced color contrast of features of interest.

First claim

What is claimed is:

1. A multispectral imaging system for imaging a specimen located on a microscope slide and stained with a plurality of chromogen stains, the multispectral imaging system comprising:
an imaging apparatus including:
an illuminator including a plurality of pulsed different color light sources that output light one at a time to sequentially produce different color light for sequentially illuminating at least a portion of the specimen, wherein each of the pulsed different color light sources illuminates the specimen and is selected to match absorption properties of a different chromogen stain from the plurality of chromogen stains,
an image capture device that captures a plurality of specimen images corresponding to the specimen being exposed to light from each one of the pulsed different color light sources without using filters, wherein each respective one of the specimen images corresponds to the specimen being exposed to only one color of light from the illuminator, and wherein the image capture device is synchronized with pulsing of the pulsed different color light sources, and
a processing device configured to:
enhance color contrast between a first feature of interest of the specimen stained with a first chromogen stain and a second feature of interest of the specimen stained with a second chromogen stain by selecting a false color for at least one of the first or second chromogen stains,
produce contrast enhanced multicolor image data of the specimen, which includes the false color for the at least one of the first or second chromogen stains, based on the specimen images captured by the image capture device, wherein each of the different chromogen stains is a different color in the contrast enhanced multicolor image data of the specimen, and wherein color contrast between the first and second features of interest in the contrast enhanced multicolor image data is greater than natural color contrast between the first and second features of interest,
output the contrast enhanced multicolor image data as a video configured for display at a frame rate greater than or equal to 2 frames per second, and
automatically detect and identify features of interest of the specimen based on the contrast enhanced multicolor image data of the specimen;

at least one lens positioned along an optical path extending from the specimen to the image capture device; and
a display in communication with the imaging apparatus and configured to display the video of the contrast enhanced multicolor image data of the specimen in real-time.

2. The multispectral imaging system of claim 1 , further comprising a microscope including a holder device holding the microscope slide, the at least one lens, and at least one ocular through which a user is capable of viewing the specimen while the display displays the multicolor image data of the specimen.

3. The multispectral imaging system of claim 2 , wherein the processing device is configured to output the contrast enhanced multicolor image data as a video configured for display at a frame rate equal to or greater than 30 frames per second.

4. The multispectral imaging system of claim 1 , further comprising a digital microscope slide scanner comprising the imaging apparatus and a slide handler mechanism, wherein the slide handler mechanism is movable to deliver one or more microscope slides to the imaging apparatus and is movable to remove one or more microscope slides from the imaging apparatus.

5. The multispectral imaging system of claim 1 , wherein each of the pulsed different color light sources includes at least one light-emitting diode.

6. The multispectral imaging system of claim 1 , wherein the plurality of pulsed different color light sources comprises:
a first light source that produces light absorbed by the first chromogen stain bound to the first feature of interest of the specimen; and
a second light source that produces light absorbed by the second chromogen stain bound to the second feature of interest of the specimen, wherein the first light source has a first mean wavelength that is different from a second mean wavelength of the second light source.

7. The multispectral imaging system of claim 6 , wherein the processing device includes a storage device that stores a first specimen image captured by the image capture device while the specimen is illuminated by the first light source and a second specimen image captured by the image capture device while the specimen is illuminated by the second light source, and wherein the processing device is configured to digitally combine image data of the first and second specimen images to produce the contrast enhanced multicolor image data of the specimen, wherein the contrast enhanced multicolor color image data of the specimen is a false color composite image of the specimen.

8. The multispectral imaging system of claim 1 , wherein the plurality of pulsed different color light sources includes at least four light sources having respective mean wavelengths that are different from another.

9. The multispectral imaging system of claim 1 , wherein the illuminator produces a plurality of energy emissions having mean wavelengths that are different from one another, and wherein a total number of the energy emissions is in a range of 4 to 8.

10. The multispectral imaging system of claim 1 , wherein the processing device produces 4 to 10 spectrally deconvolved images of the specimen and produces a false color image of the specimen based on the spectrally deconvolved images.

11. The multispectral imaging system of claim 1 , wherein each of the pulsed different color light sources includes one or more light-emitting diodes, wherein the image capture device is configured to provide monochrome images of the specimen, and wherein the processing device generates false color images based on the monochrome images.

12. The multispectral imaging system of claim 1 , wherein the processing device is configured to produce a false color composite image of the specimen generated from the specimen images.

13. The multispectral imaging system of claim 1 , wherein the processing device is configured to generate the contrast enhanced multicolor image data at a frame rate equal to or greater than 10 frames per second for viewing on the display.

14. The multispectral imaging system of claim 1 , wherein the image capture device includes a monochrome camera.

15. A computer-based imaging system for imaging a specimen located on a microscope slide, comprising:
memory for storing a sequence of program instructions; and
at least one processor with circuitry configured to execute the program instructions to cause the at least one processor to:
cause a first light source and a second light source of an illuminator to output different color light at different times to sequentially illuminate the specimen,
receive a first image of the specimen exposed to only a first color light from the illuminator, wherein the first color light is from the first light source which is characterized by a first wavelength or a first waveband selected to match at least one first chromogen bound to a first feature of interest of the specimen,
receive a second image of the specimen exposed to only a second color light from the illuminator, wherein the second color light is from the second light source which is characterized by a second wavelength or a second waveband selected to match at least one second chromogen bound to a second feature of interest of the specimen and not being exposed to the first color of light, wherein the second wavelength or the second waveband is different

Assignees

• Ventana Med Syst Inc

Inventors

• Morrison Larry
• Dietz Lou

Classifications

• H04N23/11 Primary

  for generating image signals from visible and infrared light wavelengths · CPC title

• G01N21/6458 Primary

  Fluorescence microscopy (fluorescence microscopes per se G02B21/0076 and G02B21/16) · CPC title

• H04N5/332 Primary

  Electricity · mapped topic