Abstract: An iterative process calculates the absorption and scattering coefficients of tissue from a set of diffuse reflectance measurements made with an optical spectrometer operating in the UV-VIS spectral range. The relationship between measured diffuse reflectance and the absorption and scattering coefficients is modeled using a Monte Carlo simulation.

Abstract: The subject matter described herein includes an optical assay system for intraoperative assessment of tumor margins. According to one aspect, the subject matter described herein includes a biological sample containment and illumination apparatus for holding a biological sample for illumination by a plurality of electromagnetic radiation probes. The biological sample containment and illumination apparatus includes a plurality of frame members positioned with respect to each other to form an interior space for receiving a biological sample. At least one of the plurality of frame members includes a plurality of probe receiving locations for receiving a plurality of electromagnetic radiation probes. The probe receiving locations position the probes with respect to the biological sample to allow illumination of plural locations of the biological sample by the probes.

Abstract: The presently disclosed subject matter relates to multilayered scaling methods that allow for implementation of fast Monte Carlo simulations of diffuse reflectance from multilayered turbid media. The disclosed methods employ photon trajectory information provided by only a single baseline simulation, from which the diffuse reflectance can be computed for a wide range of optical properties in a multilayered turbid medium. A convolution scheme is also incorporated to calculate diffuse reflectance for specific fiber-optic probe geometries. Also provided are systems for fast Monte Carlo simulation of diffuse reflectance of a multilayered turbid medium to rapidly determine diffuse reflectance for the multilayered turbid medium with known optical properties and for using the scaled diffuse reflectance to determine optical properties of a turbid medium having unknown optical properties.

Abstract: A reflectance instrument illuminates the surface of tissue with light of a selected wavelength and light emanating from the tissue due to reflectance is collected. The angle of illumination of tissue surface and/or collection of reflections is changed to probe at various depths beneath the surface of the tissue. The reflectance instrument may be used in a method for measuring the optical properties of a two layer diffuse media such as epithelial tissues.

Abstract: The subject matter described herein includes a method for modeling fluorescence in turbid media and methods and systems for using the model to determine intrinsic fluorescence of turbid media. According to one aspect, a method for modeling fluorescence of a turbid medium and for using the model to determine intrinsic fluorescence in the turbid medium is provided. The method includes illuminating a turbid medium of interest with an electromagnetic radiation source using a probe of a particular geometry and detecting measured fluorescence for the turbid medium using the probe. At least one set of Monte Carlo simulations is run to determine an escape energy probability map and an absorbed energy density map for the turbid medium. An indication of the intrinsic fluorescence of the turbid medium is determined using the escape probability density map and the absorbed energy density map in a manner that accounts for the geometry of the probe.

Abstract: A reflectance instrument illuminates the surface of tissue with light of a selected wavelength and light emanating from the tissue due to reflectance is collected. The angle of illumination of tissue surface and/or collection of reflections is changed to probe at various depths beneath the surface of the tissue. The reflectance instrument may be used in a method for measuring the optical properties of a two layer diffuse media such as epithelial tissues.

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: A fluorescence instrument illuminates the surface of tissue with light of a selected wavelength and light emanating from the tissue due to fluorescence is collected. The angle of illumination of tissue surface and/or collection of fluorescence is changed to probe at various depths beneath the surface of the tissue for a fluorescence layer. Three embodiments of the instrument are described.

Abstract: The presently disclosed subject matter provides methods, systems, and computer program products for optimizing a probe geometry for spectroscopic measurement in a turbid medium. According to one method, a probe geometry comprising one emitting entity for emitting electromagnetic radiation into a turbid medium and at least on collecting entity for collecting the electromagnetic radiation that has interacted with the turbid medium is selected. A simulation is performed with inputs of the probe geometry and a plurality of sets of optical property values associated with the turbid medium to generate output comprising optical parameter values measured by the probe geometry for each set of input optical property values. The measured optical parameter values are input to an inversion algorithm to produce corresponding optical properties as output.

Abstract: An iterative process calculates the absorption and scattering coefficients of tissue from a set of diffuse reflectance measurements made with an optical spectrometer operating in the UV-VIS spectral range. The relationship between measured diffuse reflectance and the absorption and scattering coefficients is modeled using a Monte Carlo simulation.

Abstract: A needle biopsy includes the step of inserting an optical spectroscopy probe in the needle and gathering optical information through a window formed in the side of the needle at its distal end. The optical probe includes an illumination optical fiber which conveys light to the tissues adjacent the side window and a detection optical fiber which collects light from the same tissues and conveys it to an optical spectroscopy instrument. Based on the results of the optical spectroscopy measurement, the optical probe may be withdrawn from the needle and a cutter advanced to acquire a sample of the tissues adjacent the side window.

Abstract: A fluorescence instrument illuminates the surface of tissue with light of a selected wavelength and light emanating from the tissue due to fluorescence is collected. The angle of illumination of tissue surface and/or collection of fluorescence is changed to probe at various depths beneath the surface of the tissue for a fluorescence layer. Three embodiments of the instrument are described.

Abstract: A fluorescence instrument illuminates the surface of tissue with light of a selected wavelength and light emanating from the tissue due to fluorescence is collected. The size of the effective illumination/collection aperture is varied to probe at various depths beneath the surface of the tissue for a fluorescence layer. Three embodiments of the instrument are described.

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: A fluorescence instrument illuminates the surface of tissue with light of a selected wavelength and light emanating from the tissue due to fluorescence is collected. The size of the effective illumination/collection aperture is varied to probe at various depths beneath the surface of the tissue for a fluorescence layer. Three embodiments of the instrument are described.

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: 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 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.