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: 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: 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: 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: Methods and apparatus for classifying tissue use features of Raman spectra and background fluorescent spectra. The spectra may be acquired in the near-infrared wavelengths. Principal component analysis and linear discriminant analysis of reference spectra may be used to obtain a classification function that accepts features of the Raman and background fluorescence spectra for test tissue and yields an indication as to the likelihood that the test tissue is abnormal. The methods and apparatus may be applied to screening for skin cancers or other diseases.

Abstract: A micro-Raman spectrometer system for use in differentiating tumor lesions from normal skin detects specific characteristics of Raman spectra indicative of cancer. A peak at 899 cm?1 and a higher intensity region in the 1325 cm?1 to 1330 cm?1 range indicate the presence of tumors. The spectrometer system may be applied for skin cancer detection and for mapping the margins of lesions. Cancer detection methods as described herein have achieved diagnostic sensitivity of 95.8% and specificity of 93.8%.

Abstract: Methods and apparatus for classifying tissue use features of Raman spectra and background fluorescent spectra. The spectra may be acquired in the near-infrared wavelengths. Principal component analysis and linear discriminant analysis of reference spectra may be used to obtain a classification function that accepts features of the Raman and background fluorescence spectra for test tissue and yields an indication as to the likelihood that the test tissue is abnormal. The methods and apparatus may be applied to screening for skin cancers or other diseases.

Abstract: Surface roughness measurements are made by illuminating a surface with coherent light to generate a speckle pattern and studying characteristics of the speckle pattern. The disclosed techniques may be applied to measuring the surface roughness of skin or other biological surfaces. Skin roughness information may be used in the diagnosis of conditions such as malignant melanoma. Methods and apparatus for measuring the coherence length of optical sources involve extracting information about speckle patterns resulting when light from the optical sources interacts with a surface having a known roughness.

Abstract: Spectral measurement devices and methods able to provide EEMs and other spectral measurements. The devices rapidly and specifically illuminate a sample and detect resulting light emanating from the sample. Such devices can use acousto-optic tunable filters (AOTFs) to selectively illuminate the sample with illumination light substantially only in a desired illumination wavelength(s). This provides high detection sensitivity, large measurement dynamic range and scans of the full 400-1000 nm light range (or more) at rates as fast as about 1 second, or even as fast as video rates. In another aspect, methods and systems relating to the analysis of autofluorescence emanating from melanin under long wavelength visible light (VIS) and near infrared (NIR) excitation.

Abstract: In one aspect, the invention provides a diagnostic method for identifying psoriatic plaques in which Porphyrins, particularly protoporphyrin IX, are elevated as compared to normal skin and skin of patients with other dermatological diseases, including other forms of psoriatic plaque. Psoriatic plaques with elevated porphyrin levels may be detected by fluorescence and spectral analysis. Endogenous porphyrins in psoriatic plaques may be activated with visible light to treat psoriatic plaques having elevated porphyrin concentrations. Skin conditions may be optimized to increase the endogenous concentration of porphyrins in psoriatic plaques. A topical formulation may be applied to psoriatic plaques to optimize skin conditions such as pH, iron concentration, temperature, hydration, calcium concentration, oxygenation, electrical conductivity and estrogen concentration to increase the concentration of endogenous porphyrins.

Abstract: A method and apparatus for controlling the dosimetry of a photodynamic therapy that involves exposing a site to be treated to treatment light in order to generate toxic products at the site and other photoproducts. Often a photosensitizer drug is administered to the patient prior to treatment or the therapy relies on the presence of endogenous photosensitizers. The method comprises the steps of selecting a photoproduct having an identifying characteristic, which can be a fluorescence peak, and monitoring the photoproduct using the identifying characteristic (e.g. fluorescence) to determine the level of the photoproduct being generated. The photodynamic therapy is then terminated when the photoproduct being monitored reaches a predetermined level. The method allows for safe treatment of a site using photodynamic therapy and ensures that overexposure to treatment light leading to damage of normal tissue or underexposure leading to ineffective treatment of the lesion does not occur.

Abstract: Apparatus for diagnosis of a skin disease site using spectral analysis includes a light source for generating light to illuminate the disease site and a probe unit optically connected to the light source for exposing the disease site to light to generate fluorescence and reflectance light. The probe unit also collects the generated fluorescence and reflectance light and transmits this light to a spectrometer to be analyzed. The spectrometer generates and displays spectral measurements of the fluorescence light and the reflectance light which in together assist the user in diagnosing the disease site. The apparatus makes use of a conventional personal computer using a plug-in spectrometer card to provide a compact and low costs system. The system performs combined fluorescence and reflectance spectral analysis in a quick and efficient manner to provide a powerful tool for dermatologic diagnosis.

Abstract: Apparatus for the diagnosis of a skin disease site by visual fluorescence inspection comprising an excitation light source for illuminating the disease site, a light guide for transmitting the excitation light directly to the disease site to generate fluorescence light and viewing goggles for processing the excitation light reflected and the fluorescence light emitted from the disease site to provide a fluorescence image of the disease site to a user. The fluorescence image is used to aid the medical assessment of skin conditions and the diagnosis of cutaneous diseases by supplementing the visual assessment of skin lesions made by the naked eye. The apparatus can be used in several modes of operation that permit the viewing of full color fluorescence images and enhanced two color images. The apparatus can also use image intensifying equipment to amplify fluorescence light so that even very weak fluorescing objects can be seen. A method for acquiring and viewing the fluorescence images is also disclosed.

Abstract: Apparatus for diagnosis of a skin disease site using spectral analysis includes a light source for generating light to illuminate the disease site and a probe unit optically connected to the light source for exposing the disease site to light to generate fluorescence and reflectance light. The probe unit also collects the generated fluorescence and reflectance light and transmits this light to a spectrometer to be analysed. The spectrometer generates and displays spectral measurements of the fluorescence light and the reflectance light which in together assist the user in diagnosing the disease site. The apparatus makes use of a conventional personal computer using a plug-in spectrometer card to provide a compact and low cost system. The system performs combined fluorescence and reflectance spectral analysis in a quick and efficient manner to provide a powerful tool for dermatologic diagnosis.