Systems and methods for performing optical spectroscopy using a self-calibrating fiber optic probe

#The subject matter disclosed herein relates to optical spectroscopy and calibration techniques pertaining to fiber optic measurement instruments. More particularly, the subject matter disclosed herein relates to systems and methods for performing optical spectroscopy using a self-calibrating fiber optic probe.

#Diffuse reflectance spectroscopy (DRS) is sensitive to the absorption and scattering properties of biological molecules in tissue and therefore can be used as a noninvasive in vivo tool to obtain quantitative information about the physiological and morphological properties (e.g., biomarkers) of human tissue. Thus, DRS can be utilized specifically as a diagnostic tool to detect various diseases that alter human tissue properties. Potential clinical applications of DRS include precancer detection and cancer diagnostics, intraoperative tumor margin assessment, and monitoring of tumor response to chemotherapy. Fiber optic probes are commonly used to deliver illumination light to, and collect diffusely reflected light from, a tissue specimen for DRS measurements. However, in order for DRS to be utilized in a clinic, frequent calibration is typically required to correct or compensate for a number of factors, such as lamp intensity fluctuations, wavelength-dependent instrument response, interdevice variations, and fiber bending losses that occur while a measurement is taken.

#Calibration techniques presently used by biophotonics researchers typically rely on measurements using power meters, reflectance standards, and/or tissue phantoms (i.e., models that simulate human tissue and blood vessels). These calibration procedures are usually performed after the clinical measurements are completed. One particular DRS calibration method involves a two-step calibration procedure that utilizes the measured spectra of a spectrally flat diffuse reflectance standard (i.e., a reflective Spectralon puck) and a phantom of known optical properties in order to obtain the absolute reflectance spectra of a tissue sample. For example, a calibrated reference phantom spectrum is obtained by dividing the collected phantom spectrum with the collected puck spectrum. Similarly, a calibrated tissue spectrum is obtained by dividing a collected tissue spectrum with a second collected puck spectrum (i.e., a 2nd spectrum measurement of the same calibration puck). More specifically, calibration is performed by dividing the tissue spectra point by point by the spectra of the puck. Afterwards, a ratio of the calibrated tissue spectrum and the calibrated reference phantom spectrum is input into an inverse Monte Carlo model, which in turn extracts the optical properties of the tissue.

#Preferred embodiments of the subject matter described herein will now be described with reference to the accompanying drawings, of which:

#FIG. 1 is a block diagram of an optical spectrometer system that utilizes a self-calibrating fiber optical probe according to an embodiment of the subject matter described herein;

#FIG. 2 is a diagram of an exemplary self-calibrating fiber optic probe according to an embodiment of the subject matter described herein;

#The subject matter described herein includes systems and methods for performing optical spectroscopy using a self-calibrating fiber optic probe. The present subject matter includes a fast, robust, and systematic calibration approach that can be used for correcting spectral data of a specimen obtained in real-time and with different instruments and probes. More specifically, the present subject matter includes a fiber optic probe with self-calibration capability configured for performing diffuse reflectance spectroscopy (DRS). The probe includes a built-in calibration channel that can be used to record the light source spectrum and instrument-fiber responses contemporaneously with tissue spectra measurements. Combined with a one-time single-reference phantom measurement, the self-calibrating fiber optic probe can provide instrument-independent optical properties.

#FIG. 1 depicts an exemplary optical DRS system 100 that includes a self-calibrating fiber optic probe 102. DRS system 100 may also include a light source 104, an imaging spectrograph 108, a charged-couple device (CCD) camera unit 110, and a processing unit 112 (e.g., a computer). In one embodiment, spectrograph 108 and CCD camera unit 110 are collectively known as a spectrometer. In one embodiment, fiber optic probe 102 comprises an illumination fiber “leg” 114 (which is coupled to light source 104), a collection fiber leg 116 (which is coupled to spectrograph 108), and a probe tip section 106, which may be used to interface with a specimen (e.g., sample 118), such a tissue mass or any turbid medium. In one embodiment, light source 104 may include a xenon lamp, a white light emitting diode (LED) source, or the like. In an alternate embodiment, a broadband light source with a monochromator (e.g., a scanning double-excitation monochromator) or simply a plurality of laser diodes may also be used in system 100 along with a plurality of photo-detectors (e.g., photodiodes) used in lieu of spectrograph 108 and CCD 110. Also, self-calibrating fiber optic probe 102 may be adapted to accommodate any probe instrument. Possible probe adaptations include, but are not limited to, side firing probes and forward firing probes.

#The illumination fiber leg 114 of probe 102 may include illumination source fiber 122, for illuminating the sample, and calibration source fiber 124, for internal calibration. In one embodiment, each of illumination source fiber 122 and calibration source fiber 124 are 600 μm diameter fibers. In another embodiment, a plurality of 200 μm diameter illumination source fibers (instead of a single 600 μm diameter illumination source fiber) and/or at least one 200 μm diameter calibration source fiber (instead of a single 600 μm diameter calibration source fiber) may be used for increased instrument flexibility. The collection fiber leg 116 may include eight detection fibers 126 that are coupled to spectrograph 108 and are configured to collect the diffusely reflected light from sample 118 at one or more wavelengths. In one embodiment, detection fibers 126 are 200 μm diameter fibers. Collection fiber leg 116 may also include at least one calibration return fiber 128 for collecting the calibration light (which, like the illumination light, is generated by light source 104) reflected by a reflective element 302 (see FIG. 3) and transmitting the reflected light to imaging spectrograph 108. In one embodiment, calibration return fiber 128 also comprises a 200 μm diameter fiber. Although cross-sectional view 123 shows one calibration return fiber 128, additional calibration return fibers may be used. For example, additional calibration return fibers may be implemented as backup return fibers (in case a primary return fiber fails) or if additional calibration channels are to be implemented in system 100. In one embodiment, all the fibers are made from the same materials (e.g., same fiber clad, core, etc.) and have the same numerical aperture (NA) for an identical bending response. In another embodiment, the at least one calibration source fiber 124 and the at least one illumination source fiber 122 are constructed from the same type of materials and include identical numerical apertures, core diameters and clad diameters and the at least one detection fiber and the at least one calibration return fiber are constructed from the same type of materials and include identical numerical apertures, core diameters and clad diameters (i.e., the source fibers may be different from the calibration return and detection fibers).