Abstract: A Raman endoscope for use in obtaining in vivo Raman spectra in the peripheral airways of the lungs and a method of constructing the Raman endoscope are disclosed. The endoscope has a tubular sheath containing a fiber bundle. The sheath has an outer diameter of less than 1.35 mm. The sheath is made of fluorinated ethylene propylene. The sheath is flexible along its length from a first end to a point along the sheath so that it can navigate sharp turns within the peripheral airways. A layer of coating covers the sheath along a terminal length and a probe tip of the fiber bundle. The terminal length extends along a length of the sheath extending from a second end opposite to the first end to the point. Terminal length is rigid to facilitate advancement of the endoscope towards the lesion of interest. Terminal length is 5 mm or less.

Abstract: Systems for confocal Raman spectroscopy of points of interest or regions of interest with concurrent imaging are disclosed. The imaging may be used for real time selection of points of interest or regions of interest for Raman spectroscopy and to monitor for unwanted motions of a sample while Raman spectra are acquired. Disclosed embodiments apply Reflectance confocal microscopy (RCM) in a confocal Raman spectroscopy system. A single laser may be used as a light source for both RCM and micro-Raman spectroscopy. A Faraday optical isolator may be applied to extract RCM signals for imaging Systems as described herein have example application for ex vivo sample and in vivo skin measurement.

Abstract: Methods and apparatus for obtaining 3D imaging of tissue involve scanning a focused laser beam in xz planes to obtain a set of xz plane images spaced apart in a y direction. The xz plane images are processed to correct distortions and motions and combined to provide 3D image data. Surface flatting is optionally performed. Imaging may be performed using a femtosecond (fs) laser beam. Different components of light returning from the tissue may be detected and processed to yield plural co-registered images using different imaging modalities, for example, reflective confocal microscopy (RCM), two photon fluorescence (TPF) and second harmonic generation (SHG).

Abstract: Systems for confocal Raman spectroscopy of points of interest or regions of interest with concurrent imaging are disclosed. The imaging may be used for real time selection of points of interest or regions of interest for Raman spectroscopy and to monitor for unwanted motions of a sample while Raman spectra are acquired. Disclosed embodiments apply Reflectance confocal microscopy (RCM) in a confocal Raman spectroscopy system. A single laser may be used as a light source for both RCM and micro-Raman spectroscopy. A Faraday optical isolator may be applied to extract RCM signals for imaging. Systems as described herein have example application for ex vivo sample and in vivo skin measurement.

Abstract: A Raman endoscope for use in obtaining in vivo Raman spectra in the peripheral airways of the lungs and a method of constructing the Raman endoscope are disclosed. The endoscope has a tubular sheath containing a fiber bundle. The sheath has an outer diameter of less than 1.35 mm. The sheath is made of fluorinated ethylene propylene. The sheath is flexible along its length from a first end to a point along the sheath so that it can navigate sharp turns within the peripheral airways. A layer of coating covers the sheath along a terminal length and a probe tip of the fiber bundle. The terminal length extends along a length of the sheath extending from a second end opposite to the first end to the point. Terminal length is rigid to facilitate advancement of the endoscope towards the lesion of interest. Terminal length is 5 mm or less.

Abstract: Examples of a spectroscopy system with a specially design ambient illumination system are disclosed. The ambient illumination system comprises one or more light emitting diodes (LEDs) that provide illumination light in the wavelength of 400-785 nm. The ambient illumination system can further comprise a filter to block light above 785 nm. The filter can be placed directly in front of LED emitters. The LEDs can be white LEDs or RGB LEDs. The spectroscopy system can further comprise a control system that can receive a signal from the spectral probe when the spectral measurements commence and can instantaneously send a signal to automatically switch off the ambient illumination system and to receive a signal from the spectral probe when the spectral measurements are terminated and automatically switch on the ambient illumination system. Examples of methods of operating the spectroscopy system and the ambient illumination system are disclosed.

Abstract: Examples of an optical standard and a calibration apparatus for calibrating or characterizing a spectroscopy system using such optical standard are disclosed. The optical standard can comprises a mixture of acetaminophen and barium sulfate, wherein a mass of the acetaminophen in the mixture is being less than a mass of the BaSO4. Such optical standard can be used in a calibration device for calibrating or characterizing a spectroscopy system. The calibration device can comprise a substrate base with a top surface and a bottom surface. The top surface can include a section for receiving the optical standard sample. The receiving section can be adhesive. The calibration device can further comprise a film that can be attached to the top surface of the substrate base to cover at least the section of the substrate where the optical standard is being placed. The calibration device can be disposed after the calibration measurements are completed.

Abstract: Examples of a spectroscopy probe for performing measurements of Raman spectra, reflectance spectra and fluorescence spectra are disclosed. The integrated spectral probe can comprise one or more light sources to provide a white light illumination to generate reflectance spectra, an excitation light to generate an UV/visible fluorescence spectra and a narrow band NIR excitation to induce Raman spectra. The multiple modalities of spectral measurements can be performed within 2 seconds or less. Examples of methods of operating the integrated spectroscopy probe disclosed.

Abstract: Methods and apparatus for video rate or near video rate quantitative imaging of tissue physiological and morphological properties from visible/NIR light spectral images obtain rapid multi-spectral reflectance images by illuminating with a series of spectra containing multiple narrow wavelength bands. An iterative light-transport based inversion algorithm may be applied for correcting the intensity of the spectral images from the geometry/coupling effect as well as from the scattering amplitude distortions. The method can produce video rate absorption as well as scattering spectral images that can be further analyzed very rapidly, using matrix-based rapid inversion algorithms to produce more detailed quantitative images containing information relevant to tissue physiology and morphology.

Abstract: A multiphoton microscope is provided. The microscope includes: an excitation source for providing an optical excitation beam at an excitation wavelength ?; a scanner for scanning the excitation beam on a sample; an objective for irradiating the sample with the excitation beam scanned by the scanner and for collecting an emission beam from the sample; a first detector for detecting a plurality of multiphoton signals; and an emission light path allowing transmission from the objective to the first detector a wavelength band limited to greater than or equal to ?/2 and less than ?, wherein the plurality of multiphoton signals have wavelengths within the wavelength band; wherein the plurality of multiphoton signals com-prises a first multiphoton signal and a second multiphoton signal of different types. Fast image capture rate multiphoton microscopes for in vivo imaging, as well as photothermolysis methods using the microscopes are also provided.

Abstract: Scanning mechanisms that have application in confocal imaging use electromagnetic actuation to move elements in an optical system. An objective lens mounted to a flexure comprising a magnetic material is actuated in the axial direction by an electromagnet coil. An optical path may pass through the coil. Scanning in transverse directions may be provided using magnetically actuated flexible beams which move the tip of an optical fiber or other pinhole in one or more transverse directions. Actuators may be actuated using driving currents that include an AC component and a DC bias component. The scanning mechanisms may be miniaturized and may be constructed to provide real-time imaging.

Abstract: Methods and apparatus for video rate or near video rate quantitative imaging of tissue physiological and morphological properties from visible/NIR light spectral images obtain rapid multi-spectral reflectance images by illuminating with a series of spectra containing multiple narrow wavelength bands. An iterative light-transport based inversion algorithm may be applied for correcting the intensity of the spectral images from the geometry/coupling effect as well as from the scattering amplitude distortions. The method can produce video rate absorption as well as scattering spectral images that can be further analyzed very rapidly, using matrix-based rapid inversion algorithms to produce more detailed quantitative images containing information relevant to tissue physiology and morphology.

Abstract: Examples of a spectroscopy probe for performing measurements of Raman spectra, reflectance spectra and fluorescence spectra are disclosed. The integrated spectral probe can comprise one or more light sources to provide a white light illumination to generate reflectance spectra, an excitation light to generate an UV/visible fluorescence spectra and a narrow band NIR excitation to induce Raman spectra. The multiple modalities of spectral measurements can be performed within 2 seconds or less. Examples of methods of operating the integrated spectroscopy probe disclosed.

Abstract: Examples of an optical standard and a calibration apparatus for calibrating or characterizing a spectroscopy system using such optical standard are disclosed. The optical standard can comprises a mixture of acetaminophen and barium sulfate, wherein a mass of the acetaminophen in the mixture is being less than a mass of the BaSO4. Such optical standard can be used in a calibration device for calibrating or characterizing a spectroscopy system. The calibration device can comprise a substrate base with a top surface and a bottom surface. The top surface can include a section for receiving the optical standard sample. The receiving section can be adhesive. The calibration device can further comprise a film that can be attached to the top surface of the substrate base to cover at least the section of the substrate where the optical standard is being placed. The calibration device can be disposed after the calibration measurements are completed.

Abstract: Examples of a spectroscopy system with a specially design ambient illumination system are disclosed. The ambient illumination system comprises one or more light emitting diodes (LEDs) that provide illumination light in the wavelength of 400-785 nm. The ambient illumination system can further comprise a filter to block light above 785 nm. The filter can be placed directly in front of LED emitters. The LEDs can be white LEDs or RGB LEDs. The spectroscopy system can further comprise a control system that can receive a signal from the spectral probe when the spectral measurements commence and can instantaneously send a signal to automatically switch off the ambient illumination system and to receive a signal from the spectral probe when the spectral measurements are terminated and automatically switch on the ambient illumination system. Examples of methods of operating the spectroscopy system and the ambient illumination system are disclosed.

Abstract: A Raman spectrometer system provides a tool for discriminating between different tissue pathologies. The tool may provide discrimination indicators for a plurality of different pairs of tissue pathologies. Improved sensitivity and specificity are achieved by basing discriminations on appropriate ranges within a Raman spectrum.

Abstract: Scanning mechanisms that have application in confocal imaging use electromagnetic actuation to move elements in an optical system. An objective lens mounted to a flexure comprising a magnetic material is actuated in the axial direction by an electromagnet coil. An optical path may pass through the coil. Scanning in transverse directions may be provided using magnetically actuated flexible beams which move the tip of an optical fiber or other pinhole in one or more transverse directions. Actuators may be actuated using driving currents that include an AC component and a DC bias component. The scanning mechanisms may be miniaturized and may be constructed to provide real-time imaging.

Abstract: A multiphoton microscope is provided. The microscope includes: an excitation source for providing an optical excitation beam at an excitation wavelength ?; a scanner for scanning the excitation beam on a sample; an objective for irradiating the sample with the excitation beam scanned by the scanner and for collecting an emission beam from the sample; a first detector for detecting a plurality of multiphoton signals; and an emission light path allowing transmission from the objective to the first detector a wavelength band limited to greater than or equal to ?/2 and less than ?, wherein the plurality of multiphoton signals have wavelengths within the wavelength band; wherein the plurality of multiphoton signals comprises a first multiphoton signal and a second multiphoton signal of different types. Fast image capture rate multiphoton microscopes for in vivo imaging, as well as photothermolysis methods using the microscopes are also provided.

Abstract: Near-infrared Raman spectroscopy can be applied to identify preneoplastic lesions of the bronchial tree. Real-time in vivo Raman spectra of lung tissues may be obtained with a fiber optic catheter passed down the instrument channel of a bronchoscope. Using prototype apparatus, preneoplastic lesions were detected with sensitivity and specificity of 96 and 91% respectively. The use of Raman spectroscopy apparatus and methods in conjunction with other bronchoscopy imaging modalities can substantially reduce the number of false positive results.

Abstract: This invention provides a body fluid detection method by using surface enhanced Raman spectroscopy. In this method, some biological macromolecules in body fluid samples could be separated with membrane electrophoresis technique firstly. Next, samples are cut off along with the substrates and touched with glacial acetic acid. Transparent colloid formed while incubating. Then add enhancing substrates and continue to incubate and stir. When solid impurities precipitated, stop incubating and stand for layering. In the end, take upper layer resulted to be tested using SERS detection method and build SERS database. This invention successfully eliminated disturbance of other complex components on the SERS detection of protein, DNA and RNA. High quality SERS spectrum obtained is beneficial to the analysis and process of SERS spectrum. Thus body fluid can be differentiated by comparing body fluid SERS spectrum belonging to the healthy people and patients.