Optics: measuring and testing – Infrared and ultraviolet
Reexamination Certificate
1999-08-05
2001-01-30
Evans, F. L. (Department: 2877)
Optics: measuring and testing
Infrared and ultraviolet
C250S339050, C348S079000, C348S166000
Reexamination Certificate
active
06181414
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to Near Infrared (NIR) spectroscopy and more particularly to a multi-channel spectral imaging module utilizing NIR for discriminating between normal and pre-cancerous cells prepared in the form of cells or cell groupings on a microscope slide.
BACKGROUND OF THE INVENTION
Automated systems for the rapid and accurate screening of cytological specimens are being developed to address cost, labour and liability issues. One such example is the development of automated systems for the well-known Pap (i.e. Papanicolaou) test. The Pap test is a screening test for evidence of pre-cancerous lesions in exfoliated cervical cells. The Pap test involves a tedious, manual examination of tens of thousands of cervical epithelial cells, and as a result is costly to apply and is subject to human error. Nevertheless, the Pap test has an enviable record of reducing cervical cancer mortality in the countries where it is applied. Thus, an automated alternative has been eagerly sought.
The most successful automated Pap test systems emulate cytotechnologists, the highly-trained professionals that screen this and other tests. As the cytotechnologist relies on the visual evaluation of cervical cells, so the automated systems depend upon some type of image analysis.
For machines, image analysis typically comprises a series of four steps. First, the microscopic image is digitized to the image into a form that may be readily used by the electronic hardware and the software instruction set for the machine. Second, the digitized image is segmented. Segmentation involves separating the relevant portions of the digitized image from the rest of the image. In most image analysis systems, segmentation comprises the most difficult and crucial step in the processing sequence. Since segmentation must e done well in advance of any pattern recognition operation, the segmentation procedure must be designed to use visual keys such as edges to find and separate the important image components. The third step is known as feature extraction. Each of the segmented regions or objects in the image is subjected to a range of mathematical measures that seek to encapsulate the visual appearance in numerical form. The fourth step known as classification involves using the numerical features to arrive at some type of conclusion about the object's identity.
Near Infrared (NIR) spectroscopy is an established technique for the extraction of quantitative measures in a wide variety of materials. Recently, NIR spectroscopy has been applied to human tissue samples in order to discriminate between cancerous or pre-cancerous tissue and normal tissue.
Most of the absorption spectra of organic compounds are generated by the vibrational overtones or the combination bands of the fundamentals of O—H (oxygen-Hydrogen), C—H (Carbon-Hydrogen), N—H (nitrogen-Hydrogen), and C—C (Carbon-Carbon) transitions. As these transitions fall in the mid-infrared regions, NIR spectra in the easily accessible range between 0.7 microns and 2.5 microns are produced. However, the strengths of these spectra are one to three orders of magnitude smaller than the associated fundamentals and therefore special care needs to be taken to recover and analyze this information.
Known research into the NIR response of normal and pre-cancerous human tissue has uncovered a host of structural and chemical changes which may be used to discriminate between normal and pre-cancerous tissues. These features include increases in glycogen content, extensive hydrogen bonding of phosphodiester groups in nucleic acids, tighter physical packing of nucleic acids, phosphorylation of C—OH groups in carbohydrates and proteins, increased disorder of methylene chains in membrane lipids, increased ratio of methyl to methylene, reduction in the hydrogen bond strength in the amide groups of &agr;-helical segments and an increase in the hydrogen bond strength in the amide groups of the &bgr;-sheet segments.
On the basis of these results, proposals for NIR-based cancer screening protocols have been made, including a screening protocol for the early detection of pre-cancerous lesions of the uterine cervix and carcinomatous breast tissue.
BRIEF SUMMARY OF THE INVENTION
The present invention provides a multi-channel spectral imaging module utilizing NIR spectroscopic techniques to produce a rapid and effective discrimination between normal and pre-cancerous cells prepared in the form cells or cell groupings on a microscope slide or similar sub-structure.
The subject invention is intended to function as part of an automated system comprising components described in co-pending patent applications entitled Automated Scanning of Microscope Slides International Patent Application No. CA96/00475 filed Jul. 18, 1996, Pipeline Processor for Medical and Biological Applications U.S. patent application Ser. 08/683,440 filed Jul. 18, 1996, Multi-Spectral Segmentation International Patent Application No. CA96/00477 filed Jul. 18, 1996, Neural-Network Assisted Multi-Spectral Segmentation International Patent Application No. CA96/00619 filed Sep. 18, 1996, Automated Focus System International Patent Application No. CA96/00476 filed Jul. 18, 1996, Window Texture Extraction International Patent Application No. CA96/00478 filed Jul. 18, 1996, Multi-Spectral Imaging System and Method for Cytology International Patent Application No. CA97/00318 filed May 9, 1997, and Pipeline Processor for Medical and Biological Image Analysis International Patent Application No. CA97/00878 filed Nov. 20, 1997.
In one aspect, the present invention comprises a multi-channel spectral imaging module for an automated testing system for cytological applications. According to this aspect of the invention, one or two of the channels in the imaging system comprise NIR (Near Infrared) channels. The NIR channels augment the visible spectrum images produced by a multi-spectral camera system and provide new and useful channels of information. The NIR channels are used to improve segmentation performance, to create a new set of features for classification, or as discrimination measures independent of the visible light channels. According to another aspect of the invention, restricting the use of the NIR channels to regions of the samples that contain nuclear material improves the effective signal-to-noise ratio of the measurement over bulk tissue measurements thereby improving the discrimination capability of the system. In another aspect, a pair of differential NIR channels (one channel acting as an interrogator, ,the other channel providing a reference) are utilized to provide a high-speed and real-time scan of cellular material to quickly discriminate between normal and abnormal cells or tissue and may be extended to other important diagnostic properties of the cells.
The NIR channels are effective for producing rapid and effective discrimination between normal and pre-cancerous cells prepared in the form cells or cell groupings on a microscope slide or similar sub-structure.
In a first aspect, the present invention provides a multi-channel spectral imaging module for an automated testing system for cytological application, said multi-channel spectral imaging module comprising: (a) a light source module for illuminating a cytological specimen, said light source including a visible light source and an infrared light source and a control input for actuating said visible and infrared light sources; (b) an optical imaging module for receiving illuminated images of said cytological specimen and including a lens system for focusing said illuminated images; (c) a prism module for receiving said illuminated images from said optical imaging module, said prism module including three prism elements for producing three respective image channels in the visible spectrum and a fourth prism element for producing an image channel in the infrared spectrum, and said prism module further including a digitizer for each of said channels for converting the image into an output signal.
In a second aspect, the present
Maclean Daniel S.
Raz Ryan S.
Rosenblatt Gordon
Evans F. L.
Morphometrix Technologies Inc
Ridout & Maybee
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