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: An apparatus and method for detecting radiation damage in an area of brain tissues, where the area of brain tissues has at least a first region containing brain tissues damaged from radiation exposure and a second region containing no brain tissues damaged from radiation exposure. In one embodiment, the method includes the steps of illuminating in vivo the area of brain tissues with a coherent light at an incident wavelength, &lgr;0, between 330 nm and 360 nm, collecting electromagnetic emission returned from the illuminated brain tissues, and identifying a first peak of intensity of the collected electromagnetic emission at a first wavelength, &lgr;1, and a second peak of intensity of the collected electromagnetic emission at a second wavelength, &lgr;2, wherein &lgr;0, &lgr;1, and &lgr;2 satisfy the following relationship of &lgr;1>&lgr;2>&lgr;0.

Abstract: Tissue types (e.g. tumorous or normal) are determined using optical spectroscopy. Autofluorescence and diffuse reflectance spectra are generated by separately illuminating a tissue surface area with monochromatic light and white light. A peak in autofluorescence intensity (F) is provided around 460 nm from both from normal and tumorous human brain tissue with 337 nm monochromatic light excitation. Separation between white/gray matter and brain tumors is provided by certain combined F-Rd spectrum numerical values, especially certain ratios of F and Rd between 400 nm-600 nm. Numerical values based on certain combinations of unequal exponential powers of F and Rd are essentially unaffected by the superficial blood contamination. In addition, diffuse reflectance intensity (Rd) between 650 nm and 800 nm from white/gray matter was significantly stronger than that from primary and secondary brain tumors and is used with the combined spectrum numerical value to enhance accurate determinations.

Abstract: The present invention provides methods of directly stimulating neural tissue with optical energy. By stimulating neural tissue at wavelengths, laser pulses, and spot sizes disclosed herein, nerve stimulation may be used to uniquely stimulate neural tissue in way not afforded by other means of stimulation. It can allow basic scientists to study the properties of individual neurons or populations of neurons without piercing tissue with fragile microelectrodes. Furthermore, responses of neural tissue can be studied in a pure fashion without contamination by electrical artifact commonly seen with electrical stimulation. With respect to clinical uses, optical stimulation can be used to map function in subsections of peripheral nerves as an aid to operative repair. Finally, stimulation with optical energy does not require physical contact with the nerve which may be an advantage clinically when physical manipulation of neural tissue is not desired.

Abstract: Optical spectroscopy for brain tumor demarcation was investigated in this study. Fluorescence and diffuse reflectance spectra were measured from normal and tumorous human brain tissues in vitro. A fluorescence peak was consistently observed around 460 nm (±10 nm) emission from both normal and tumorous brain tissues using 337 nm excitation. Intensity of this fluorescence peak (F460) from normal brain tissues was greater than that from primary brain tumorous tissues. In addition, diffuse reflectance (Rd) between 650 nm and 800 nm from white matter was significantly stronger than that from primary and secondary brain tumors. A good separation between gray matter and brain tumors was found using the ratio of F460 and Rd at 400 nm-600 nm. Two empirical discrimination algorithms based on F (400 nm-600 nm), Rd (600 nm-800 nm), and F (400 nm-600 nm)/Rd (400 nm-600 nm) were developed. These algorithms yielded an average sensitivity and specificity of 96% and 93%, respectively.

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: 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: An optical probe is disclosed which is suitable for rapidly measuring Raman spectra in vivo. The probe is designed to minimize interfering Raman and fluorescence signals generated within the probe itself. In addition, the probe design is compact, making it particularly suited for use in confined spaces such as body cavities. In one embodiment, the probe is employed to detect tissue abnormalities such as cervical cancers and precancers.

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: Apparatus and in vivo methods to distinguish normal and abnormal cervical tissue and to detect cervical intraepithelial neoplasia (CIN) in a diagnostic cervical tissue sample. Induced fluorescence intensity spectra from known normal cervical tissue and a diagnostic tissue sample are obtained from the same patient. Peak fluorescence intensity values for normal tissue samples are averaged, as are slope measurements from predetermined portions of spectra induced in both known normal cervical tissue and the diagnostic tissue sample. Peak fluorescence intensities of diagnostic tissue spectra are divided by average peak fluorescence intensity values for normal tissue in the same patient to yield relative peak fluorescence intensity values. Normal and abnormal cervical tissues are distinguished using a predetermined empirical discriminant function of slope measurements derived from normal tissue spectra and relative peak fluorescence intensity measurements in the same patient.

Abstract: Apparatus and in vivo methods to distinguish normal and abnormal cervical tissue and to detect cervical intraepithelial neoplasia (CIN) in a diagnostic cervical tissue sample. Induced fluorescence intensity spectra from known normal cervical tissue and a diagnostic tissue sample are obtained from the same patient. Peak fluorescence intensity values for normal tissue samples are averaged, as are slope measurements from predetermined portions of spectra induced in both known normal cervical tissue and the diagnostic tissue sample. Peak fluorescence intensities of diagnostic tissue spectra are divided by average peak fluorescence intensity values for normal tissue in the same patient to yield relative peak fluorescence intensity values. Normal and abnormal cervical tissues are distinguished using a predetermined empirical discriminant function of slope measurements derived from normal tissue spectra and relative peak fluorescence intensity measurements in the same patient.