Abstract: Optical biopsy staining panels for in vivo or in situ fluorescent staining of optical tissue (or other appropriate tissue), e.g., for the purpose of a direct biopsy such as an optical biopsy. The stain panels may feature a combination of a nuclear stain and a cytoplasmic stain, as a means of functioning as an invivo or in situ hematoxylin and eosin (H&E) stain. Examples of said stains may include anthracyclines such as Daunomcibin, acriflavines like Proflavine, anthracenediones such as Mitoxantrone, phenothiazines like Methylene Blue, and tri- and tetra-heterocyclic dyes like Fluorescein, Phloxine B, Phenol Red, Rose Bengal, Congo Red, and Indigo Carmine.

Abstract: A falloposcope is described, and a method of screening a patient for fallopian tube and/or ovarian cancer with the falloposcope. The falloposcope can perform optical imaging, including fluorescence imaging and/or optical coherence tomography (OCT), and optionally include a channel for a sampling wire, within a diameter of about 0.7 millimeter. The method includes inserting the falloposcope through a lumen of vagina, cervix, uterus, and fallopian tube so a tip of the falloposcope is in proximity to a first fallopian tube or ovary of the patient; providing fluorescence stimulus wavelength through an illumination fiber of the falloposcope while imaging light at fluorescence emission wavelength through a coherent fiber bundle to form fluorescence emissions images; and determining suspect tissue. Then the sampling wire is used to collect cells from the suspect tissue for karyotype and other analysis.

Abstract: A falloposcope is described, as is a method of screening a patient for fallopian tube and/or ovarian cancer with the Falloposcope. The falloposcope has an optical imaging subsystem capable of performing optical and fluorescence imaging, and an optical coherence tomography (OCT) channel, with a diameter of about 0.7 millimeter. The method includes inserting the falloposcope through a lumen of vagina, cervix, uterus, and fallopian tube such that a tip of the falloposcope is in proximity to a first fallopian tube or ovary of the patient; providing at least one fluorescence stimulus wavelength through an illumination fiber of the falloposcope, while imaging light at one or more fluorescence emission wavelengths through a coherent fiber bundle to form fluorescence emissions images; and determining suspect tissue from the fluorescence emission images.

Abstract: Methods for reliable identification of low-contrast lesions within a tissue of a subject comprise delivering an excitation signal to the tissue, wherein the excitation signal is selected to stimulate tissue to produce autofluorescence and/or reflectance. The autofluorescence and/or reflectance is detected, and ratiometric images are produced based on the autofluorescence and/or reflectance images. An imaging system is provided which is configured to carry out such methods, irradiating tissue at a various possible excitation wavelengths, such as UV excitation wavelengths below 300 nm, to elicit fluorescence from specific native fluorophores.

Abstract: A falloposcope is described, as is a method of screening a patient for fallopian tube and/or ovarian cancer with the Falloposcope. The falloposcope has an optical imaging subsystem capable of performing optical and fluorescence imaging, and an optical coherence tomography (OCT) channel, with a diameter of about 0.7 millimeter. The method includes inserting the falloposcope through a lumen of vagina, cervix, uterus, and fallopian tube such that a tip of the falloposcope is in proximity to a first fallopian tube or ovary of the patient; providing at least one fluorescence stimulus wavelength through an illumination fiber of the falloposcope, while imaging light at one or more fluorescence emission wavelengths through a coherent fiber bundle to form fluorescence emissions images; and determining suspect tissue from the fluorescence emission images.

Abstract: Methods for reliable identification of low-contrast lesions within a tissue of a subject comprise delivering an excitation signal to the tissue, wherein the excitation signal is selected to stimulate tissue to produce autofluorescence and/or reflectance. The autofluorescence and/or reflectance is detected, and ratiometric images are produced based on the autofluorescence and/or reflectance images. An imaging system is provided which is configured to carry out such methods, irradiating tissue at a various possible excitation wavelengths, such as UV excitation wavelengths below 300 nm, to elicit fluorescence from specific native fluorophores.

Abstract: Systems and methods for diagnosing epithelial neoplasia and other conditions includes, in a representative embodiment, providing the human eyes with a filter to observe the autofluorescence of a tissue sample. Using optimized wavelengths from a filtered light source, a sample is illuminated. The radiation from the sample is filtered to enhance the contrast between a normal sample and a diseased sample observable by the human eye.

Abstract: Fluorescence spectral data acquired from tissues in vivo or in vitro is processed in accordance with a multivariate statistical method to achieve the ability to probabilistically classify tissue in a diagnostically useful manner, such as by histopathological classification. The apparatus includes a controllable illumination device for emitting electromagnetic radiation selected to cause tissue to produce a fluorescence intensity spectrum. Also included are an optical system for applying the plurality of radiation wavelengths to a tissue sample, and a fluorescence intensity spectrum detecting device for detecting an intensity of fluorescence spectra emitted by the sample as a result of illumination by the controllable illumination device. The system also include a data processor, connected to the detecting device, for analyzing detected fluorescence spectra to calculate a probability that the sample belongs in a particular classification.

Abstract: Systems and methods for diagnosing epithelial neoplasia and other conditions includes, in a representative embodiment, providing the human eyes with a filter to observe the autofluorescence of a tissue sample. Using optimized wavelengths from a filtered light source, a sample is illuminated. The radiation from the sample is filtered to enhance the contrast between a normal sample and a diseased sample observable by the human eye.

Abstract: Fluorescence spectral data acquired from tissues in vivo or in vitro is processed in accordance with a multivariate statistical method to achieve the ability to probabilistically classify tissue in a diagnostically useful manner, such as by histopathological classification. The apparatus includes a controllable illumination device for emitting electromagnetic radiation selected to cause tissue to produce a fluorescence intensity spectrum. Also included are an optical system for applying the plurality of radiation wavelengths to a tissue sample, and a fluorescence intensity spectrum detecting device for detecting an intensity of fluorescence spectra emitted by the sample as a result of illumination by the controllable illumination device. The system also include a data processor, connected to the detecting device, for analyzing detected fluorescence spectra to calculate a probability that the sample belongs in a particular classification.

Abstract: Methods and apparatus for generating multispectral images of tissue. The multispectral images may be used as a diagnostic tool for conditions such as cervical cancer detection and diagnosis. Primary radiation is produced with an illumination source. The primary radiation is filtered to select a first wavelength and a first polarization. Tissue is illuminated with the filtered primary radiation to generate secondary radiation, which is filtered to select a second wavelength and a second polarization. The filtered secondary radiation is collected with a detector, and a plurality of multispectral images of the tissue is generated according to different combinations of first and second wavelengths and first and second polarization with an analysis unit in operable relation with the detector. Apparatus utilizing the invention include endoscopes and colposcopes.

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: A method and apparatus for characterizing tissue of epithelial lined viscus in vivo including, for example, the endocervical canal. The method comprises illuminating an interior surface of the viscus with electromagnetic radiation wavelengths to produce a plurality of fluorescence intensity spectra, detecting a plurality of emission wavelengths from the fluorescence intensity spectra, and characterizing the epithelial viscus tissue as a function of the emission wavelengths.

Abstract: Methods and apparatus for assessing the size of a scattering element of a sample. Primary radiation is generated from a source. The primary radiation is polarized to produce polarized primary radiation. The polarized primary radiation is directed to the sample to generate reflected radiation. The reflected radiation is directed through a polarizer to produce filtered reflected radiation, the polarizer being configured to select reflected radiation parallel and perpendicular to the polarization of the polarized primary radiation. The filtered radiation is detected, and a depolarization ratio is calculated using the detected filtered radiation. The size of the scattering element is calculated using the depolarization ratio.

Abstract: Methods and apparatus for performing fluorescence and spatially resolved reflectance spectroscopy on a sample. A sample is irradiated with a fluorescence excitation fiber and radiation is collected from the sample with a fluorescence collection fiber and detected to form fluorescence spectra. The sample is also illuminated with a reflectance illumination fiber and reflected light from the sample is collected at a plurality of collection positions and detected to form spatially resolved reflectance spectra. The fibers may form a probe arranged in concentric sections. The spectra are analyzed by pre-processing and reducing the dimensionality of the spectral data.

Abstract: Methods and apparatus for assessing the size of a scattering element of a sample. Primary radiation is generated from a source. The primary radiation is polarized to produce polarized primary radiation. The polarized primary radiation is directed to the sample to generate reflected radiation. The reflected radiation is directed through a polarizer to produce filtered reflected radiation, the polarizer being configured to select reflected radiation parallel and perpendicular to the polarization of the polarized primary radiation. The filtered radiation is detected, and a depolarization ratio is calculated using the detected filtered radiation. The size of the scattering element is calculated using the depolarization ratio.

Abstract: Methods and apparatus for generating multispectral images of tissue. The multispectral images may be used as a diagnostic tool for conditions such as cervical cancer detection and diagnosis. Primary radiation is produced with an illumination source. The primary radiation is filtered to select a first wavelength and a first polarization. Tissue is illuminated with the filtered primary radiation to generate secondary radiation, which is filtered to select a second wavelength and a second polarization. The filtered secondary radiation is collected with a detector, and a plurality of multispectral images of the tissue is generated according to different combinations of first and second wavelengths and first and second polarization with an analysis unit in operable relation with the detector. Apparatus utilizing the invention include endoscopes and colposcopes.

Abstract: A method for using acetic acid as a signal enhancing contrast agent during fluorescence spectroscopy of normal and neoplastic tissue, particularly epithelium. In one aspect, the invention includes a method of detecting tissue abnormality in a diagnostic tissue sample in a patient, comprising the steps of obtaining a first fluorescence intensity spectrum from the diagnostic tissue sample; thereafter, applying acetic acid to the diagnostic tissue sample in sufficient concentration to alter the response of such diagnostic tissue sample to electromagnetic radiation for at least an effective period of time; during the effective period of time, obtaining a second fluorescence intensity spectrum from the diagnostic tissue sample; determining a parameter indicative of a change between the first and second fluorescence emission intensity spectra; and analyzing the determined parameter to determine a probability that the diagnostic tissue sample is normal or abnormal.