Abstract: Methods and apparatus for segmenting cell nuclei in medical images apply first and second trained machine learning algorithms. The first trained machine learning algorithm processes a medical image to provide center locations of cell nuclei depicted in the image. The second machine learning algorithm processes each of a plurality of patches of the image. Each of the patches correspond to one of the plurality of center locations. Processing each patch yields a nuclear boundary corresponding to the corresponding one of the center locations. The methods and apparatus allow associating individual pixels of the image with one or more than one nuclei and have been shown to be effective for instance segmentation of nuclei in clusters of overlapping cell nuclei.

Abstract: A fiber-based polarization sensitive optical coherence tomography (PS-OCT) system uses a new polarization diversity detection (PDD) scheme and requires no active polarization modulating components. Retardation of the sample can be determined from amplitudes of arbitrarily-oriented x- and y-components of the reflected light. A hybrid custom 50/50 coupler with single-mode fiber inputs and polarization maintaining (PM) fiber outputs combines light from sample and reference arms of an interferometer. Another embodiment provides a system adapted to provide co-registered autofluorescence-optical coherence tomography (AF-OCT) imaging. AF excitation light is introduced and collected AF light is extracted at a fiber optic rotary joint (FORJ) equipped with an embedded dichroic mirror. A probe tip that uses a clad fiber to supply light to a focusing element provides enhanced OCT and AF performance.

Abstract: A fiber-based polarization sensitive optical coherence tomography (PS-OCT) system uses a new polarization diversity detection (PDD) scheme and requires no active polarization modulating components. Retardation of the sample can be determined from amplitudes of arbitrarily-oriented x- and y-components of the reflected light. A hybrid custom 50/50 coupler with single-mode fiber inputs and polarization maintaining (PM) fiber outputs combines light from sample and reference arms of an interferometer. Another embodiment provides a system adapted to provide co-registered autofluorescence-optical coherence tomography (AF-OCT) imaging. AF excitation light is introduced and collected AF light is extracted at a fiber optic rotary joint (FORJ) equipped with an embedded dichroic mirror. A probe tip that uses a clad fiber to supply light to a focusing element provides enhanced OCT and AF performance.

Abstract: An optical computed-tomography microscope for three-dimensional (3-D) imaging employs tomographic reconstruction for image acquisition. The microscope has an optical scanner to vary an angle at which a light beam passes through a specimen. A method for limited-angle computed-tomography reconstruction applies a transform to produce an image from a number of projections. The image is iteratively feedback-corrected.

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: 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: 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: The present invention relates to the use of 5-(p-methoxyphenyl)-1,2-dithiole-3-thione or of a pharmaceutical derivative thereof for the preparation of a medicament for preventing lung cancer in a mammalian subject, especially for preventing or reducing the appearance of new dysplastic lesions, or the progression of pre-existing dysplastic lesions in the subject, or for improving regression of existing dysplastic lesions.

Abstract: Systems and methods are described for improved diagnostic fluorescence and reflectance. A method of detecting tissue abnormality in a tissue sample in vivo detects a set of reflectance spectra emitted from a tissue sample as a result of illumination with an excitation light from a fiber optic probe that has at least one collection fiber positioned at a source-detector separation, and determining if the tissue sample is normal or abnormal based on the resulting reflectance spectra. Another method of detecting tissue abnormality in a tissue sample in vivo includes illuminating the tissue sample in vivo with at least one electromagnetic radiation wavelength selected to cause the tissue sample to produce a set of fluorescence intensity spectra indicative of tissue abnormality, detecting the resulting fluorescence intensity spectra, and determining if the tissue sample is normal or abnormal based on the resulting fluorescence intensity spectra.

Abstract: In one aspect, the invention provides a diagnostic method for identifying psoriatic plaques in which Porphyrins, particularly protoporphyrin IX, are elevated as compared to normal skin and skin of patients with other dermatological diseases, including other forms of psoriatic plaque. Psoriatic plaques with elevated porphyrin levels may be detected by fluorescence and spectral analysis. Endogenous porphyrins in psoriatic plaques may be activated with visible light to treat psoriatic plaques having elevated porphyrin concentrations. Skin conditions may be optimized to increase the endogenous concentration of porphyrins in psoriatic plaques. A topical formulation may be applied to psoriatic plaques to optimize skin conditions such as pH, iron concentration, temperature, hydration, calcium concentration, oxygenation, electrical conductivity and estrogen concentration to increase the concentration of endogenous porphyrins.

Abstract: A method and apparatus for controlling the dosimetry of a photodynamic therapy that involves exposing a site to be treated to treatment light in order to generate toxic products at the site and other photoproducts. Often a photosensitizer drug is administered to the patient prior to treatment or the therapy relies on the presence of endogenous photosensitizers. The method comprises the steps of selecting a photoproduct having an identifying characteristic, which can be a fluorescence peak, and monitoring the photoproduct using the identifying characteristic (e.g. fluorescence) to determine the level of the photoproduct being generated. The photodynamic therapy is then terminated when the photoproduct being monitored reaches a predetermined level. The method allows for safe treatment of a site using photodynamic therapy and ensures that overexposure to treatment light leading to damage of normal tissue or underexposure leading to ineffective treatment of the lesion does not occur.

Abstract: Apparatus for diagnosis of a skin disease site using spectral analysis includes a light source for generating light to illuminate the disease site and a probe unit optically connected to the light source for exposing the disease site to light to generate fluorescence and reflectance light. The probe unit also collects the generated fluorescence and reflectance light and transmits this light to a spectrometer to be analyzed. The spectrometer generates and displays spectral measurements of the fluorescence light and the reflectance light which in together assist the user in diagnosing the disease site. The apparatus makes use of a conventional personal computer using a plug-in spectrometer card to provide a compact and low costs system. The system performs combined fluorescence and reflectance spectral analysis in a quick and efficient manner to provide a powerful tool for dermatologic diagnosis.

Abstract: Apparatus for diagnosis of a skin disease site using spectral analysis includes a light source for generating light to illuminate the disease site and a probe unit optically connected to the light source for exposing the disease site to light to generate fluorescence and reflectance light. The probe unit also collects the generated fluorescence and reflectance light and transmits this light to a spectrometer to be analysed. The spectrometer generates and displays spectral measurements of the fluorescence light and the reflectance light which in together assist the user in diagnosing the disease site. The apparatus makes use of a conventional personal computer using a plug-in spectrometer card to provide a compact and low cost system. The system performs combined fluorescence and reflectance spectral analysis in a quick and efficient manner to provide a powerful tool for dermatologic diagnosis.

Abstract: An apparatus and method for imaging diseases in tissue are presented. The apparatus employs a light source for producing excitation light to excite the tissue to generate autofluorescence light and for producing illumination light to generate reflected and back scattered light (remittance light) from the tissue. Optical sensors are used to receive the autofluorescence light and the remittance light to collect an autofluorescence light image and a remittance light image. A filter acts to integrate the autofluorescence image over a range of wavelengths in which the autofluorescence intensity for normal tissue is substantially different from the autofluorescence intensity for diseased tissue to establish an integrated autofluorescence image of the tissue. The remittance light image provides a background image to normalize the autofluorescence image to account for image non-uniformity due to changes in distance, angle and illumination intensity.

Abstract: An apparatus and method for imaging diseases in tissue are presented. The apparatus employs a light source for producing excitation light to excite the tissue to generate autofluorescence light and for producing illumination light to generate reflected and back scattered light (remittance light) from the tissue. Optical sensors are used to receive the autofluorescence light and the remittance light to collect an autofluorescence light image and a remittance light image. A filter acts to integrate the autofluorescence image over a range of wavelengths in which the autofluorescence intensity for normal tissue is substantially different from the autofluorescence intensity for diseased tissue to establish an integrated autofluorescence image of the tissue. The remittance light image provides a background image to normalize the autofluorescence image to account for image non-uniformity due to changes in distance, angle and illumination intensity.

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 fibreoptic 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.