Methods and apparatus for imaging using a light guide bundle...

Surgery – Endoscope – Having imaging and illumination means

Reexamination Certificate

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C600S182000, C600S181000, C385S116000, C359S298000

Reexamination Certificate

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06663560

ABSTRACT:

FIELD OF THE INVENTION
The field of the present invention is imaging using a light guide bundle.
BACKGROUND OF THE INVENTION
Microscopes magnify objects or samples, which can be stationary and moving. One type of microscope is a confocal microscope, which uses a very small spot, or pinhole, of light to make its image of the target. Typically, the spot is scanned across the target in a pointwise, digital fashion and the image is made by combining the points of return light emanating from the target (the return light can be, for example, reflected light, fluorescent light, or an exotic form of light such as a Raman spectrum, and can be found in any desirable region of the electromagnetic spectrum, such as ultraviolet (UV) light, blue light, visible light, near-infrared (NIR) light and infrared (IR) light).
The confocal geometry of the illumination pinhole, the object, and the detection pinhole give a higher resolution image than a conventional widefield microscope. In some embodiments, confocal microscopy can improve the spatial resolution about 1.3 times. See, e.g., U.S. Pat. No. 5,587,832. Confocal microscopy also improves the “up and down” (i.e., z-axis or axial) resolution, which gives rise to an extremely useful optical sectioning capability, which means that images can be obtained at different depths, and thus 3-D images and volume reconstruction can be obtained.
In order to obtain the pointwise image, confocal microscopes can either move a specimen and keep the optics fixed in place, or they can keep the specimen fixed and move the light beam, for example by scanning the beam using special rotating aperture disks or other beam scanners. See U.S. Pat. Nos. 4,802,748, 5,067,805, 5,099,363, 5,162,941. Other confocal scanning systems have used a laser beam rastered with rotating mirrors to scan a specimen or a laser beam that scans a slit rather than a spot; such slit scanning increases imaging speed but slightly degrades resolution. See U.S. Pat. No. 5,587,832.
Confocal microscopes typically use a bulky design in which several large components—including a laser system as the light source, detection pinholes, x-y beam steering devices, and an optical detector—must be carefully maintained in precise alignment. In these systems, the specimen or target to be imaged is placed on a stage as in a conventional microscope. These limitations make the confocal microscope cumbersome, inflexible and inconvenient for imaging specimens which are not easily accessible or easily placed on a microscope stage. In other words, present confocal systems are designed for in vitro imaging of biological specimens in the lab instead of imaging tissues in the body, in vivo.
Several approaches have been proposed to permit in vivo imaging. See, e.g., T. Dabbs and M. Glass, “Fiber-optic confocal microscope: FOCON,”
Applied Optics
, vol. 31, pp. 3030-3035, 1992; L. Giniunas, R. Juskatis, and S. V. Shatalin, “Scanning fiber-optic microscope,”
Electronic Letters
, vol. 27, pp. 724-725, 1991; L. Giniunas, R. Juskatis, and S. V. Shatalin, “Endoscope with optical sectioning capability,”
Applied Optics
, vol. 32, pp. 2888-2890, 1993; D. L. Dickensheets and G. S. Kino, “Micromachined scanning confocal optical microscope,”
Optics Letters
, vol. 21, pp. 764-766, 1996; D. L. Dickensheets and G. S. Kino, “Miniature scanning confocal microscope,” U.S. Pat. No. 5,907,425 (continuation of U.S. Pat. No. 5,742,419), May 1999; A. F. Gmitro and D. Aziz, “Confocal microscopy through a fiber-optic imaging bundle,”
Optics Letters
, vol. 18, pp. 565-567, 1993; Y. S. Sabharwal, A. R. Rouse, L. Donaldson, M. F. Hopkins, and A. F. Gmitro, “Slit-scanning confocal microendoscope for high-resolution in vivo imaging, Applied Optics, vol. 38, pp. 7133-7144, 1999; R. Juskaitis, T. Wilson, and T. F. Watson, “Confocal microscopy using optical fibre imaging bundles,”
Proceedings of SPIE
, vol. 2655, pp. 92-94, 1996; U.S. Pat. No. 5,587,832; PCT/CA98/00993, Publication No. WO 99/22262. None of these systems provide as high a quality of image as could be desired for various aspects of microscopy.
Thus, there has gone unmet a need for improved microscopy systems, including confocal microscopy systems, wherein the systems can provide high quality images of desired targets in locations where the positioning of the target might not be carefully controlled, including in vivo targets. The present invention provides these and other advantages.
SUMMARY OF THE INVENTION
The present invention comprises microscopes and methods that have significant advantages in controlling the light that contacts a sample and/or that is detected emanating from a sample. The microscopes and methods, which preferably relate to confocal microscopes and further preferably confocal endoscopes for in vivo imaging, comprise a spatial light modulator in the illumination and/or detection light path so that light transmitted to the target, for example via a bundle of light guides, is transmitted substantially only into the cores of the light guide bundle and not into inter-core areas such as the cladding surrounding the light guides or filler between the light guides in the bundle. This may reduce the amount of noise or stray light in the image from the target tissue, thereby enhancing the sensitivity, contrast or resolution of the image, in at least one of the x-y directions and in the z-direction, and provides other related advantages. The present invention may also provide systems comprising only a single light guide bundle in a microendoscope and can reduce cross-talk between light guides.
In one aspect, the present invention provides a viewing system comprising a spatial light modulator and a light guide bundle having a proximal end and a distal end, wherein spatial light modulator is optically connected to the proximal end of the light guide bundle in a same conjugate image plane as the proximal end such that the spatial light modulator controls the location of light impinging on the proximal end. In some embodiments, the viewing system of comprises an endoscope or the light guide bundle comprises at least 100 light guides. The endoscope can be a confocal microscopy endoscope. The spatial light modulator can be operably connected to a controller comprising computer-implemented programming able to set to an on-state pixels of the spatial light modulator corresponding to cores of corresponding light guides in the light guide bundle to provide on-pixels and able to set to an off-state pixels corresponding to inter-core areas of the light guide bundle to provide off-pixels.
In other embodiments, a plurality of selected groups of the on-pixels are in the on-state, the selected groups being spaced apart such that light emanating from the distal end of a first light guide corresponding to a first selected group of on-pixels does not substantially interfere with light emanating from the distal end of a second light guide corresponding to a second selected group of on-pixels, and substantially all other pixels of the spatial light modulator are in the off-state. Typically, at least 3 different pixels of the spatial light modulator correspond to each core of substantially all of the corresponding light guides. The viewing system can further comprise a pixelated detector optically connected to receive light emanating from the proximal end of the light guide bundle and the controller further comprises computer-implemented programming that distinguishes between light emanating from the light guides corresponding to on-pixels of the spatial light modulator and light emanating from other light guides. The computer-implemented programming can additionally ignores light emanating from the other light guides.
In further embodiments, the controller further comprises computer-implemented programming that detects light emanating from the other light guides to provide out-of-focus data and the programming incorporates the out-of-focus data with the light emanating from the light guides corresponding to the on-pixels to provide an enhanced image. The out-of-focus data can be fit using t

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