Abstract: A method and system for normalizing optical spectra using a non-uniform segment normalization. A spectrum is obtained and is represented as a function of wavelength as an amplitude at each of a plurality of wavelengths. At least one segment of the spectrum is selected, each selected segment being bounded by an upper wavelength and a lower wavelength. A normalization factor is computed as the sum of the areas for each of the selected segments. The spectrum is normalized by dividing at least one amplitude of the spectrum by the normalization factor. Segments can be selected with different wavelength ranges, that is, segments can be non-uniform. Test specimens can be categorized based on an analysis of normalized spectra. In particular, the specimen to be tested can be human cervical tissue, and the state of health of the tissue can be determined.

Abstract: Methods and apparatus are provided for determining a characteristic of a sample of a material by the interaction of electromagnetic radiation with the sample. The apparatus includes an optical assembly and a protective barrier. The optical assembly sequentially illuminates a plurality of volume elements in the sample with an intensity distribution in the sample that drops off substantially monotonically from a first region in a first optical path and collects electromagnetic radiation emanating from each of the volume elements. The optical assembly collects the electromagnetic radiation emanating from each of the volume elements with a collected distribution that drops off substantially monotonically from a second region in a second optical path. The first and second regions at least partially overlap in each of the volume elements. The optical assembly can be configured as a probe, to be directed to the evaluation of a sample of a biological material.

Abstract: The invention provides an apparatus and methods for determining whether spectral data obtained from a region of a tissue sample are affected by an artifact. Artifacts include, for example, lighting artifacts such as glare and shadow and obstruction artifacts, such as blood, a speculum, a smoke tube, or other obstruction. Additionally, the invention provides an apparatus and methods for obtaining redundant spectral data of a given region of a sample. A redundant set of spectral data is useful where one or more artifacts affect some but not all sets of the spectral data, such that the redundant set of data is unaffected by the artifact and is representative of the tissue. An embodiment of the invention comprises using representative spectral data in diagnosing a condition of a region of tissue.

Abstract: The invention provides an apparatus and methods for determining whether spectral data obtained from a region of a tissue sample are affected by an artifact. Artifacts include, for example, lighting artifacts such as glare and shadow and obstruction artifacts, such as blood, a speculum, a smoke tube, or other obstruction. Additionally, the invention provides an apparatus and methods for obtaining redundant spectral data of a given region of a sample. A redundant set of spectral data is useful where one or more artifacts affect some but not all sets of the spectral data, such that the redundant set of data is unaffected by the artifact and is representative of the tissue. An embodiment of the invention comprises using representative spectral data in diagnosing a condition of a region of tissue.

Abstract: The invention provides methods for determining the probability that a given region of a tissue sample contains tissue of a given category, such as CIN 1 (cervical intraepithelial neoplasia, grade 1), CIN 2/3 (cervical intraepithelial neoplasia grades 2 and/or 3), normal squamous, normal columnar, and metaplasia, for example. The invention provides increased diagnostic accuracy by combining a plurality of statistical classification techniques. Furthermore, in one embodiment, the invention comprises combining one or more statistical techniques with one or more non-statistical classification techniques.

Abstract: The invention provides a system and methods for in-situ identification of one or more regions of tissue at which there is a likelihood of disease. The invention generally relates to methods and devices for acquiring, analyzing, processing, and displaying optical data and diagnostic results from a patient sample. For example, methods of the invention comprise obtaining spectral and visual data from a patient sample, calibrating the data, compensating for sample motion, arbitrating between redundant data sets, identifying potentially non-representative data, analyzing the data, and displaying the diagnostic results. The invention provides the option of real-time data processing and diagnosis.

Abstract: The invention provides methods for calibrating spectral data acquisition systems. These calibration methods produce spectral data sufficiently accurate for use in tissue classification algorithms. The invention improves the accuracy of spectral-based tissue classification schemes, in part, by properly accounting for spatial variations, instrument-to-instrument variations, and patient-to-patient variations in the acquisition of spectral data from tissue samples. Effects that are accounted for include, for example, stray light effects, electronic background effects, variation in light energy delivered to a tissue sample, spatial heterogeneities of the illumination source, chromatic aberrations of the scanning optics, variation in wavelength response of the collection optics, and efficiency of the collection optics.

Abstract: The invention provides methods for displaying diagnostic results obtained from a tissue sample. In general, the invention assigns tissue-class probability values to discrete regions of a patient sample, and creates an overlay for displaying the results. The overlay facilitates display of the tissue class probabilities in a way that reflects the diagnostic relevance of the data. For example, methods of the invention comprise applying filtering and color-blending techniques in order to facilitate display of diagnostic results.

Abstract: The invention provides methods of enhancing tissue sample images by filtering luminance values from an input image and transforming the filtered values to produce an enhanced image for use in diagnostic applications. Preferred methods of the invention provide image enhancement by filtering luminance values of an image that correspond to sample regions that are obstructed or are otherwise not of diagnostic interest, and applying a mathematical transformation based on luminance values from regions that are not filtered out. In this way, image correction is substantially based on portions of the image that are of diagnostic relevance.

Abstract: The invention provides methods for processing tissue-derived optical data for use in a classification algorithm. Methods of the invention comprise application of image masks for automatically identifying ambiguous or unclassifiable optical data. The optical data may comprise, for example, spectral data and/or acetowhitening kinetic data used in a tissue classification scheme. The invention improves the accuracy of tissue classification, in part, by properly identifying and accounting for image data from tissue regions that are affected by an obstruction and/or regions that lie outside a diagnostic zone of interest.

Abstract: The invention provides methods of focusing an instrument for the acquisition of optical data from a tissue sample. Methods of the invention allow rapid focusing in the context of a diagnostic procedure in which rapid data acquisition is desirable. For example, inventive methods allow a user to focus an optical instrument quickly enough to obtain data within an optimal window of time following application of a chemical agent to the tissue. In one embodiment, a user focuses an optical instrument by aligning laser spots projected onto a tissue sample within rings that are superimposed at predetermined locations within the user's visual field. Preferred methods of the invention further comprise automatic validation to detect whether the spots are sufficiently well-aligned.

Abstract: The invention provides methods for determining a characteristic of a tissue sample, such as a state of health, using spectral data and/or images obtained within an optimal period of time following the application of a chemical agent to the tissue sample. The invention provides methods of determining such optimal windows of time. Similarly, the invention provides methods of determining other criteria for triggering the acquisition of an optical signal for classifying the state of health of a region of a tissue sample.

Abstract: Methods and apparatus are provided for determining a characteristic of a sample of a material by the interaction of electromagnetic radiation with the sample. The apparatus includes an optical assembly and a protective barrier. The optical assembly sequentially illuminates a plurality of volume elements in the sample with an intensity distribution in the sample that drops off substantially monotonically from a first region in a first optical path and collects electromagnetic radiation emanating from each of the volume elements. The optical assembly collects the electromagnetic radiation emanating from each of the volume elements with a collected distribution that drops off substantially monotonically from a second region in a second optical path. The first and second regions at least partially overlap in each of the volume elements. The optical assembly can be configured as a probe, to be directed to the evaluation of a sample of a biological material.

Abstract: A system and method for the in situ discrimination of healthy and diseased tissue. A fiberoptic based probe is employed to direct ultraviolet illumination onto a tissue specimen and to collect the fluorescent response radiation. The response radiation is observed at three selected wavelengths, one of which corresponds to an isosbestic point. In one example, the isosbestic point occurs at about 431 nm. The intensities of the observed signals are normalized using the 431 nm intensity. A score is determined using the ratios in a discriminant analysis. The tissue under examination is resected or not, based on the diagnosis of disease or health, according to the outcome of the discriminant analysis.

Abstract: The present invention relates to systems and methods for examining a sample using a substantially monostatic, substantially confocal optical system comprising transmitting optics that focus an illuminating light upon the sample and receiving optics that collect light emitted from the sample following illumination thereof. In certain embodiments, the receiving optics may be arranged circumferentially around the light path traversed by the illuminating light. In certain embodiments, video apparatus may be included to produce images or to align the system in proximity to the target tissue. The systems and methods of the present invention may be directed towards the examination of a body tissue to provide a medical diagnosis.

Abstract: The invention provides methods for processing tissue-derived spectral data for use in a tissue classification algorithm. Methods of the invention comprise application of spectral and/or image masks for automatically separating ambiguous or unclassifiable spectral data from valid spectral data. The invention improves the accuracy of tissue classification, in part, by properly identifying and accounting for spectral data from tissue regions that are affected by an obstruction and/or regions that lie outside a diagnostic zone of interest.

Abstract: The invention provides methods and systems for diagnosing disease in a sample by monitoring optical signals produced by samples in response to the chemical agents. Preferred methods comprise application of multiple chemical agents that interact to alter an optical signal from the sample. Methods and systems of the invention also comprise monitoring an optical signal from an endogenous chromophore upon application of a chemical agent to a sample. Methods and systems of the invention also comprise the use of triggers, atomizers and image alignment to enhance the results of methods described herein.

Abstract: The present invention relates to systems and methods for examining a sample using a substantially monostatic, substantially confocal optical system comprising transmitting optics that focus an illuminating light upon the sample and receiving optics that collect light emitted from the sample following illumination thereof. In certain embodiments, the receiving optics may be arranged circumferentially around the light path traversed by the illuminating light. In certain embodiments, video apparatus may be included to produce images or to align the system in proximity to the target tissue. The systems and methods of the present invention may be directed towards the examination of a body tissue to provide a medical diagnosis.

Abstract: A method and a system is provided for discriminating between healthy cervical tissue and pathologic cervical tissue based on the fluorescence response of the tissue to laser excitation (LIF) and the backscatter response to illumination by white light (in the spectral range of 360 to 750 nm). Combining LIF and white light responses, as well as evaluating a spatial correlation between proximate cervical tissue sites in conjunction with a statistically significant “distance” algorithm, such as the Mahalanobis distance between data sets, can improve the discrimination between normal and abnormal tissue. The results may be displayed in the form of a map of the cervix representing the suspected pathology.