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 apparatuses for detecting a condition of a sample (including cervical cancers and pre-cancers) through reflectance and/or fluorescence imaging. A sample is obtained. One or more metallic nanoparticles and/or one or more quantum dots are obtained. The one or more metallic nanoparticles and/or one or more quantum dots are coupled to one or more biomarkers of the sample that are associated with the condition. A reflectance and/or fluorescence image of the sample is then taken. The image(s) exhibit characteristic optical scattering from the one or more metallic nanoparticles and/or characteristic fluorescence excitation from the one or more quantum dots to signal the presence of the one or more biomarkers. In this way, the condition can be readily screened or diagnosed.

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: Apparatus for receiving and positioning optical components. The apparatus includes a substrate, one or more mounting slots, and one or more springs. The one or more mounting slots are formed in the substrate, and each mounting slot includes a mounting slot wall. At least one of the mounting slots is adapted to receive an optical component. At least one of the mounting slots is coupled to one of the springs.

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: An apparatus and methods for fiber optic confocal imaging systems. A plurality of fibers are in communication with a scan system that controllably deflects incident radiation into the fibers in a raster pattern. An index matching agent reduces specular reflections from the fibers.

Abstract: The present invention involves the use of fluorescence spectroscopy in the diagnosis of cervical cancer and precancer. Using multiple illumination wavelengths, it is possible to (i) differentiate normal or inflamed tissue from squamous intraepithelial lesions (SILs) and (ii) to differentiate high grade SILs from non-high grade SILs. The detection may be performed in vitro or in vivo. Multivariate statistical analysis was employed to reduce the number of fluorescence excitation-emission wavelength pairs needed to re-develop algorithms that demonstrate a minimum decrease in classification accuracy. Fluorescence at excitation-emission wavelength pairs was used to redevelop and test screening and diagnostic algorithms that have a similar classification accuracy to those that employ fluorescence emission spectra at three excitation wavelengths.

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.

Abstract: A method for using acetic acid as a contrast agent during reflectance confocal imaging of normal and neoplastic tissue, particularly epithelium. In one aspect, the invention includes a method of using acetic acid as a contrast agent for confocal imaging of cells, including applying acetic acid to the diagnostic tissue sample in sufficient concentration to induce a small scale alteration of the index of refraction of nuclei in the cells; and imaging such cells using a reflectance confocal imaging system.

Abstract: An apparatus and methods for spectroscopic detection of tissue abnormality, particularly precancerous cervical tissue, using neural networks to analyze in vivo measurements of fluorescence spectra. The invention excites fluorescence intensity spectra in both normal and abnormal tissue. This fluorescence spectroscopy data is used to train a group (ensemble) of neural networks, preferably radial basis function (RBF) neural networks. Once trained, fluorescence spectroscopy data from unknown tissue samples is classified by the trained neural networks. This process is used to differentiate pre-cancers from normal tissues, and can also be used to differentiate high grade pre-cancers from low grade pre-cancers. One embodiment of the invention is able to distinguish pre-cancerous tissue from both normal squamous tissue (NS) and normal columnar (NC) tissue in a single-stage of analysis.

Abstract: A method and apparatus for detecting tissue abnormality, particularly precancerous cervical tissue, through fluorescence or Raman spectroscopy, or a combination of fluorescence and Raman spectroscopy. In vivo fluorescence measurements were followed by in vitro NIR Raman measurements on human cervical biopsies. Fluorescence spectra collected at 337, 380 and 460 nm excitation were used to develop a diagnostic method to differentiate between normal and dysplastic tissues. Using a fluorescence diagnostic method, a sensitivity and specificity of 80% and 67% were observed for differentiating squamous intraepithelial lesions (SILs) from all other tissues. In accordance with another aspect of the invention, using Raman scattering peaks observed at selected wavenumbers, SILs were separated from other tissues with a sensitivity and specificity of 88% and 100%. In addition, inflammation and metaplasia samples are correctly separated from the SILs.

Abstract: Early diagnosis of cervical precancer is an important clinical goal. Optical spectroscopy has been suggested as a new technique to overcome limitations of current clinical practice. Herein, NIR Raman spectroscopy is applied to the diagnosis of cervical precancers. Using algorithms based on empirically selected peak intensities, ratios of peak intensities and a combination of Principal Component Analysis (PCA) for data reduction and Fisher Discriminant Analysis (FDA), normal tissues, inflammation and metaplasia were distinguishable from low grade and high grade precancers. The primary contributors to the tissue spectra appear to be collagen, nucleic acids, phospholipids and glucose 1-phosphate. These results suggest that near infrared Raman spectroscopy can be used effectively for cervical precancer diagnosis.

Abstract: A multispectral imaging probe delivers a range of wavelengths of excitation light to a target and collects a range of expressed light wavelengths. The multispectral imaging probe is adapted for mobile use and use in confined spaces, and is sealed against the effects of hostile environments. The multispectral imaging probe comprises a housing that defines a sealed volume that is substantially sealed from the surrounding environment. A beam splitting device mounts within the sealed volume. Excitation light is directed to the beam splitting device, which directs the excitation light to a target. Expressed light from the target reaches the beam splitting device along a path coaxial with the path traveled by the excitation light from the beam splitting device to the target. The beam splitting device directs expressed light to a collection subsystem for delivery to a detector.

Abstract: A multispectral imaging method and apparatus adapted for use in determining material properties, especially properties characteristic of abnormal non-dermal cells. A target is illuminated with a narrow band light beam. The target expresses light in response to the excitation. The expressed light is collected and the target's response at specific response wavelengths to specific excitation wavelengths is measured. From the measured multispectral response the target's properties can be determined.

Abstract: An optical probe is disclosed which is suitable for rapidly measuring Raman spectra in vivo. The probe is designed to minimize interfering Raman and fluorescence signals generated within the probe itself. In addition, the probe design is compact, making it particularly suited for use in confined spaces such as body cavities. In one embodiment, the probe is employed to detect tissue abnormalities such as cervical cancers and precancers.