Abstract: A beam-shaper for transforming a MM beam with the flattop intensity distribution profile includes an end block which is fused to a downstream end of a fiber outputting the MM beam along a path within a laser head. The beam-shaper further has a collimator mounted to the laser head downstream from the end block. The collimated MM beam is then focused on the working zone with a beam waist characterized by a Gaussian intensity profile. The Gaussian region may be provided in the vicinity of the beam waist by positioning the collimator so that the Gaussian region of the MM flattop beam is located inside the end block and in the focal plane of the collimator. Alternatively, the Gaussian region may be provided within the waist by using a diffractive optical element which transforms the flattop distribution profile into a donut-shaped profile.

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: 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 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: Small Molecule Metabolite Reporters (SMMRs) for use as in vivo glucose biosensors, sensor compositions, and methods of use, are described. The SMMRs include boronic acid-containing xanthene, coumarin, carbostyril and phenalene-based small molecules which are used for monitoring glucose in vivo, advantageously on the skin.

Abstract: An apparatus for measuring hematocrit of a subject's blood includes an optical source that generates an optical beam that illuminates subcutaneous vessels under a subject's skin. An optical element is positioned to receive a near field portion of the optical beam that is reflected from the subcutaneous vessels under the subject's skin. A scanning mechanism positions the optical element relative to the subcutaneous vessels under the subject's skin over a plurality of relative distances. An optical detector generates a plurality of electrical signals in response to detecting the near field portion of the optical beam that is reflected from the subcutaneous vessels under the subject's skin at the plurality of relative distances between the optical element and the subcutaneous vessels. A processor determines a value of hematocrit in the subcutaneous vessels illuminated by the optical beam from the plurality of electrical signals generated by the optical detector.

Abstract: A system and method for determining an in vivo property of a tissue or blood is described. The in vivo property may be a hematocrit value, a hemoglobin concentration, or a combination thereof. The system can automatically determine a location of a subcutaneous blood vessel. Based on the automatically determined location, the system illuminates the blood vessel with a light beam and detects light resulting from the illumination. The system determines the in vivo property based on the detected light. Alternatively, or in combination, the system displays an image corresponding to a spatial relationship between a subcutaneous blood vessel and a light beam. Based on the image, an operator can adjust the light beam with respect to the blood vessel to have a selected spatial relationship. The system determines an in vivo property based on the illumination of the blood vessel when the light beam has the selected spatial relationship.

Abstract: A system and method for determining an in vivo property of a tissue or blood is described. The in vivo property may be a hematocrit value, a hemoglobin concentration, or a combination thereof. The system can automatically determine a location of a subcutaneous blood vessel. Based on the automatically determined location, the system illuminates the blood vessel with a light beam and detects light resulting from the illumination. The system determines the in vivo property based on the detected light. Alternatively, or in combination, the system displays an image corresponding to a spatial relationship between a subcutaneous blood vessel and a light beam. Based on the image, an operator can adjust the light beam with respect to the blood vessel to have a selected spatial relationship. The system determines an in vivo property based on the illumination of the blood vessel when the light beam has the selected spatial relationship.

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: The invention provides methods and systems for monitoring effects of chemical agents on 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 invention provides methods and systems for monitoring effects of chemical agents on 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: 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 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 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: 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: 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 invention provides methods and systems for monitoring effects of chemical agents on 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 invention provides methods and systems for monitoring effects of chemical agents on 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 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.