Optical: systems and elements – Compound lens system – Microscope
Reexamination Certificate
1998-03-09
2001-10-16
Spyrou, Cassandra (Department: 2872)
Optical: systems and elements
Compound lens system
Microscope
C359S368000
Reexamination Certificate
active
06304373
ABSTRACT:
DESCRIPTION
The present invention relates to imaging system which enhance image quality by reducing noise which reduces contrast in images, especially images obtained from turbid media, such as encountered in biological specimens, and especially dermatological tissue wherein keratin is present. Media, which are turbid, may be characterized by having a high RMS refractive index variation and high scattering cross sections.
The invention is especially suitable for use in confoca. microscopy and especially in raster scanning confocal microscopes such as the Vivascope confocal scanning raster microscope sold by Lucid Technologies, Inc. of Henrietta, N.Y., U.S.A and described in an article by M. Rajadhyaksha, et al. entitled “
In Vivo Coa,focal Scanning Laser Microscopy of Human Skin, Melanin Provides Strong Contrast
” that appeared in the Journal of Investigative Dermatology, Volume 104, No. 6, pg. 1 (June 1995) and also the subject matter of an article by M. Rajadhyaksha and James M. Zavislan which appeared on Laser Focus World, pg. 119 (February, 1996) and in the hand-held scanning laser microscope which is the subject matter of U.S. patent application Ser. No. 08/650,684 filed May 20, 1996 in the name of James M. Zavislan, et al, now U.S. Pat. No. 5,788,639, issued Aug. 4, 1998. The invention is also useful in optical coherence tomography or interference microscopy.
It has been discovered in accordance with the invention, that by illuminating a medium with low spatial coherence laser radiation, especially transverse multi-mode radiation which propagates and in the TEM
01
or higher modes, images obtained from return light from an image plane or section within a specimen, by responding to the intensity of the return light, have reduce image distortion. Distortion produced by scattering sites adjacent to the image plane or section tends to be minimized or at least reduced to a constant value, while optical signals due to index variations and other optical activity within the image plane or section (region of interest) are actually detected. Thus, correlated noise from scatterers, which produces optical distortion and especially speckle effects in the image, is reduced, thereby enhancing the quality of the image. The focal region (image plane or section) may be at the surface of the specimen or embedded in the specimen and the incident light is focused at a laser beam waist into components of opposite phases. Outside the focal plane (in the section) the components overlap and destructively interfere before detection. Noise due to scattering sites away from the focal region may occur, whether the region is at the surface or embedded in the specimen. The section being imaged, especially in imaging of biological tissue, can be of the thickness of a cell, for example, about five microns.
Regions adjacent to the section of interest may have an abundance of scatterers, both behind and ahead of the section in the direction of propagation of the illuminating beam, which is incident on the section. These potential scattering sources are illuminated by the same optical field that illuminate the region of interest. There is a finite probability that return light from these scatterers will pass through a confocal aperture and reach the detector as optical signals from which the image of the section of interest is constructed. The spurious return light may manifest itself as speckle in the image. The use of multi-mode laser illumination, in accordance with the invention, has been found to reduce such distortion, and especially speckle distortion, thereby providing additional contrast and enhancing the image quality.
Confocal microscopes have heretofore used single mode lasers which propagate usually in the TEM
00
mode, in order to obtain a single component spot or dot in the focal plane. As described in RE 34,214 issued Apr. 6, 1993 to Carlsson, the laser beam is focused at a single spot in the focal plane which is conjugate optically to the confocal aperture. The present invention uses a plurality of spots due to lobes (components) of multi-mode, preferably TEM
01
or higher modes, which lobes are in out of phase amplitude relationship where such modes are focussed (at the laser beam waist-which lies in the focal plane). The lobes overlap outside the focal plane, thus reducing the spurious, undesirable returns from scattering sites outside of the focal plane, which defines the section of the specimen of interest. The above referenced applications use polarization techniques to shear the beams which, like the multi-mode illumination, produces spots which are spaced apart in the focal plane and overlap and cancel spurious reflections (as from scatters) outside the focal plane, but required polarization prisms and lenses. More specifically my prior applications, Ser. Nos. 08-966046 and 60/072,334, referenced above, further enhance image quality in imaging systems by utilizing circularly polarized beams focused on the image plane thereby obtaining noise reduction in the image, especially speckle noise which may be attributable to scatterers adjacent to the image plane. The spots may be laterally offset or vertically offset and provide different modalities for imaging.
The noise reduction system described herein also has application to optical coherence imaging often referred to as optical coherence-domain reflectivity, optical coherence tomograph or optical coherence microscopy. (See Schmitt. et al,
Optical characterization of dense tissues using low-coherence interferometry
, SPIE, Vol. 1889, pps. 197-211, July, 1992). In this imaging modality, a low temporal coherence source is used to illuminate an interferometer with a phase-modulated reference arm and a sample arm. In the sample arm, a focussing objective directs light into a sample, often a turbid biological specimen. Only light which is scattered from a depth in the tissue that has equal optical path as the optical path of the reference arm constructively interferes at the detector to provide an electronic signal that represents the optical signal from the sample. This coherence requirement eliminates the need for a confocal pinhole to select the image plane inside the tissue. Optical coherence imaging however, suffers from the same deleterious effect of adjacent scatters as does confocal imaging. This effect is reduced, however, by the multi-mode laser illumination and detection system previously described.
Accordingly, it is the principal object of the present invention to provide improved imaging systems, and especially imaging systems using confocal microscopy, and more especially improved laser scanning confocal microscopes.
It is a further object of the present invention to provide improved confocal microscopes and especially improved laser scanning confocal microscopes.
It is a still further object of the invention to provide improved confocal laser scanning microscopes which provide images of biological tissue, and especially dermatological tissue.
It is a still further object of the invention to provide improved instruments using optical coherence interferometry.
Briefly described, a system embodying the invention enables viewing a section of a medium. Light is received by and returned from the section and from sites adjacent to the section. The system utilizes transverse multi-mode laser illumination to provide light which is incident on the medium. This incident illumination is focused in the section being imaged to provide spots which are spaced from each other in the plane of the section of interest. The spots are due to the lobes or components of the incident multi-mode laser light which are in opposing (180°) phase amplitude relationship. The lobes overlap outside of the focal plane, thereby providing interference of light returned from the sites (scatterers) adjacent to the section being imaged. The image may be constructed in response to the intensity of the return light.
REFERENCES:
patent: 4975237 (1990-12-01), Brown
patent: 5386317 (1995-01-01), Corle et al.
patent: 5557452 (1996-09-01), Harris
patent: 5589936 (199
Lucid Inc.
Lukacher Kenneth J.
Lukacher Martin
Spyrou Cassandra
Treas Jared
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