Abstract: Apparatus and methods relating to microscopes having specific control of the light that contacts a sample and/or a light detector, such as the eye of the user, a charge couple device or a video camera. The improved control includes enhanced, selective control of the angle of illumination, quantity of light and location of light reaching the sample and/or detector. The microscopes comprise one or more spatial light modulators in the illumination and/or detection light path of the microscope at one or both of the conjugate image plane of the aperture diaphragm of the objective lens and the conjugate image plane of the sample.

Abstract: Computer programs, systems and the like related to processing, segmenting and feature normalizing digital images. The images are of cells and the methods are useful for the detection of malignancy-associated changes (MAC) in cells, which can be used for the detection of cancer. The programs and methods detect cancer in one tissue by detecting MAC in another tissue, such as associated tissues or non-associated tissues. Examples of associated tissues include nipple aspirates or ductal washings to detect breast cancer, and sputum or bronchial lavage to detect lung cancer. Examples of non-associated tissues include buccal mucosa to detect lung or breast cancer.

Abstract: Endoscopes and other viewing devices that control the light that contacts a sample and/or that is detected emanating from a sample. The viewing devices are particularly well suited for in vivo imaging, although other uses are also included. The viewing devices, and methods related thereto, comprise a spatial light modulator in the illumination and/or detection light path so that light transmitted to the target via a bundle of light guides or optical system is transmitted substantially only into the cores of the light guide bundle and not into the cladding surrounding the light guides, filler between the light guides in the bundle, or undesired light guides. Also, methods and apparatus for mapping the pixels of the spatial light modulator to the cores of the light guides in the bundle (preferably at least 3 pixels (e.g., at least 3 mirrors for a digital micromirror device) for each core), as well as for mapping the light guides of one light guide bundle to another.

Abstract: Endoscopes and other viewing devices that control the light that contacts a sample and/or that is detected emanating from a sample. The viewing devices are particularly well suited for in vivo imaging, although other uses are also included. The viewing devices, and methods related thereto, comprise a spatial light modulator in the illumination and/or detection light path so that light transmitted to the target via a bundle of light guides or optical system is transmitted substantially only into the cores of the light guide bundle and not into the cladding surrounding the light guides, filler between the light guides in the bundle, or undesired light guides. Also, methods and apparatus for mapping the pixels of the spatial light modulator to the cores of the light guides in the bundle (preferably at least 3 pixels (e.g., at least 3 mirrors for a digital micromirror device) for each core), as well as for mapping the light guides of one light guide bundle to another.

Abstract: Apparatus for acquiring in vivo images of a site of interest within the internal organs of a body. The apparatus includes an elongate, flexible catheter. The catheter is introducible into the body and has a first end that remains external to the body and a second and positionable adjacent the site of interest. A movable scanning unit having at least one sensor for acquiring images is housed adjacent the second end of the catheter. There is a drive mechanism to control movement of the movable scanning unit from the first external end of the catheter to acquire multiple images of the site of interest. The drive mechanism has a control element extending the length of the catheter lumen adapted for linear movement within the lumen to generate linear or rotational movement of the scanning unit.

Abstract: Microvolume liquid dispensers that provide simple and inexpensive approaches to making cytology microarrays. In some embodiments, the dispensers comprise tips that comprise an outer sleeve, typically shaped like a funnel, that holds a reciprocating needle or pin. The tip of the pin slightly extends beyond the distal opening of the outer sleeve in one position, and is retracted in another position. When the pin is in the distal position the pin contacts the inner surfaces of the sleeve and blocks cytology liquid from flowing through the opening of the sleeve. Thus the pin and sleeve cooperate to form a reservoir behind the blockage. When the pin is pushed up into the sleeve, for example by touching the tip to a glass slide, a passage is formed between the outer surface of the pin and the inner surface of the sleeve. The liquid in the reservoir then flows through the passage and onto the slide.

Abstract: Microarray readers and methods that compensate for target spots that are too dim or too bright for the microarray reader to accurately measure. The readers adjust the amount of light directed at or received from specific non-acceptable target spots, such that dim spots receive more excitation light and overly bright spots receive less. This increases or decreases, respectively, their measured brightness, which in turn effectively increases the range over which a microarray reader can accurately measure the spots, and can also improve the signal-to-noise ratio and other aspects of the measurements.

Abstract: A method for detecting malignancy-associated changes. A sample of cells is obtained and stained to identify the nuclear DNA material. The sample is imaged with a digital microscope. Objects of interest are identified in the sample of cells based on the intensity of the pixels that comprise the object versus the average intensity of all pixels in the slide image. An exact edge is located for each object and variations in the illumination intensity of the microscope are compensated for. A computer system calculates feature values for each object and, based on the value of the features, a determination is made whether the cell exhibits malignancy-associated changes or not.

Abstract: Apparatus and methods relating to microscopes having specific control of the light that contacts a sample and/or a light detector, such as the eye of the user, a charge couple device or a video camera. The improved control includes enhanced, selective control of the angle of illumination, quantity of light and location of light reaching the sample and/or detector. The microscopes comprise one or more spatial light modulators in the illumination and/or detection light path of the microscope at one or both of the conjugate image plane of the aperture diaphragm of the objective lens and the conjugate image plane of the sample.

Abstract: Lighting systems comprising a spectrum former upstream from a reflective pixelated spatial light modulator (reflective SLM), the SLM reflecting substantially all of the light in the spectrum into at least two different light paths, that do not reflect back to the light source or the spectrum former. At least one of the light paths acts as a projection light path and transmits desired light out of the lighting system. The lighting systems provide virtually any desired color(s) and intensity(s) of light, and avoid overheating problems by deflecting unwanted light and other electromagnetic radiation out of the system or to a heat management system. The systems can be part of another system, a luminaire, or any other suitable light source. The systems can provide virtually any desired light, from the light seen at the break of morning to specialized light for treating cancer or psoriasis, and may change color and intensity at speeds that are perceptually instantaneous.

Abstract: Apparatus and methods that improve the depth resolution of confocal microscopy images using out-of-focus information from within the focal plane of interest (from the x-y direction) and/or from planes above and below the focal plane of interest (from the z-direction). The interaction of (a) a reflective surface or other light-emanating material and (b) the PSF formed by a confocal microscope results in “out-of-focus” information in, above and below the focal plane; this “out-of-focus” information can be measured. Comparing the measurements in the x-y plane, preferably at a plurality of z-positions, can improve the resolution along each of the x, y, and z-axes, increase the number of the photons used in the system, thus improving the signal to noise ratio, and help correct for aberrations, such as spherical aberrations or other optical aberrations, in the optical system of a microscope.

Abstract: Methods and apparatus for detecting the possible rejection of a transplanted tissue by a host. The transplanted tissue is subjected to illumination with light to induce fluorescence. The light can be ultraviolet light, visible light or infrared light, which can be used alone or in any combination, which means one, two or three forms of light may be used together. The induced fluorescence is collected and analyzed, then compared with fluorescence that is obtained using the same procedure for a known, healthy tissue that is the same type of tissue as the transplanted tissue. Also provided are methods and apparatus related to the determination of probe orientation and the need for biopsy.

Abstract: Apparatus for the diagnosis of a skin disease site by visual fluorescence inspection comprising an excitation light source for illuminating the disease site, a light guide for transmitting the excitation light directly to the disease site to generate fluorescence light and viewing goggles for processing the excitation light reflected and the fluorescence light emitted from the disease site to provide a fluorescence image of the disease site to a user. The fluorescence image is used to aid the medical assessment of skin conditions and the diagnosis of cutaneous diseases by supplementing the visual assessment of skin lesions made by the naked eye. The apparatus can be used in several modes of operation that permit the viewing of full color fluorescence images and enhanced two color images. The apparatus can also use image intensifying equipment to amplify fluorescence light so that even very weak fluorescing objects can be seen. A method for acquiring and viewing the fluorescence images is also disclosed.

Abstract: A method for detecting malignancy-associated changes. A sample of cells is obtained and stained to identify the nuclear DNA material. The sample is imaged with a digital microscope. Objects of interest are identified in the sample of cells based on the intensity of the pixels that comprise the object versus the average intensity of all pixels in the slide image. An exact edge is located for each object and variations in the illumination intensity of the microscope are compensated for. A computer system calculates feature values for each object and, based on the value of the features, a determination is made whether the cell exhibits malignancy-associated changes or not.

Abstract: Apparatus for imaging diseases in tissue comprising a light source for generating excitation light that includes wavelengths capable of generating characteristic autofluorescence for abnormal and normal tissue. A fiber-optic illuminating light guide is used to illuminate tissue with light that includes at least the excitation light thereby exciting the tissue to emit the characteristic autofluorescence. An imaging bundle collects emitted autofluorescence light from the tissue. The autofluorescence light is filtered into spectral bands in which the autofluorescence intensity for abnormal tissue is substantially different from normal tissue and the autofluorescence intensity for abnormal tissue is substantially similar to normal tissue. An optical system is used to intercept the filtered autofluorescence light to acquire at least two filtered emitted autofluorescence images of the tissue.

Abstract: A system for detecting cancerous or precancerous lesions directs light produced from a mercury arc lamp into an illumination guide of an endoscope. Autofluorescence light produced by the tissue under examination is divided into red and green spectral bands by a dichroic mirror. Light in the red and green spectral band is applied to a pair of image intensified CCD cameras. The output of the camera that receives light in the red spectral band is coupled to a red video input of a color video monitor. Light produced by the camera that receives light in the green spectral band is coupled to the blue and green video inputs of the video monitor. The system produces a false color display, whereby healthy tissue appears cyan in color and cancerous or precancerous lesions appear reddish in color. The image displayed allows the operator to see the lesions within the context of the underlying tissue structures.