Compact beveled fiber optic probe design for enhanced depth discrimination in epithelial tissues.

We report the development and evaluation of a simple compact probe that incorporates multiple beveled fibers for depth sensitive detection of spectroscopic signals in vivo. We evaluated three probes with bevel angles 35, 40, and 45 degrees for their collection efficiency and depth resolution using a thin highly scattering white substrate and found that a 40 degree bevel provides the best characteristics for depth-resolved spectroscopy. The depth sensitivity of the probe with 40 degree beveled fibers was then evaluated using multilayer phantoms with scattering properties mimicking precancerous tissue and in vivo on normal human oral mucosa. The results demonstrate that the use of multiple beveled fibers has the capability to simultaneously collect scattering spectra from a range of depths within epithelial tissue that has the potential to provide further significant improvement of detection and monitorin of epithelial precancers.

[1]  Angela A. Eick,et al.  Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics. , 1998, Applied optics.

[2]  R. Richards-Kortum,et al.  Microanatomical and Biochemical Origins of Normal and Precancerous Cervical Autofluorescence Using Laser-scanning Fluorescence Confocal Microscopy¶ , 2003, Photochemistry and photobiology.

[3]  Rebecca Richards-Kortum,et al.  Light scattering from collagen fiber networks: micro-optical properties of normal and neoplastic stroma. , 2007, Biophysical journal.

[4]  S. Shapshay,et al.  Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma , 2003, Cancer.

[5]  M Fitzmaurice,et al.  Endoscopic detection of dysplasia in patients with Barrett's esophagus using light-scattering spectroscopy. , 2000, Gastroenterology.

[6]  J. Roodenburg,et al.  Non-invasive measurement of the morphology and physiology of oral mucosa by use of optical spectroscopy. , 2007, Oral oncology.

[7]  Linda T. Nieman,et al.  Optical sectioning using a fiber probe with an angled illumination-collection geometry: evaluation in engineered tissue phantoms. , 2004, Applied optics.

[8]  S. Robbins,et al.  Pathologic basis of disease , 1974 .

[9]  Nirmala Ramanujam,et al.  Effect of fiber optic probe geometry on depth-resolved fluorescence measurements from epithelial tissues: a Monte Carlo simulation. , 2003, Journal of biomedical optics.

[10]  Michele Follen,et al.  Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer. , 2005, Journal of biomedical optics.

[11]  Rebecca Richards-Kortum,et al.  Reflectance spectroscopy for diagnosis of epithelial precancer: model-based analysis of fiber-optic probe designs to resolve spectral information from epithelium and stroma. , 2005, Applied optics.

[12]  J. Mourant,et al.  Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic-scattering spectroscopy. , 1997, Physics in medicine and biology.

[13]  Vadim Backman,et al.  Assessment of blood supply in superficial tissue by polarization-gated elastic light-scattering spectroscopy. , 2006, Applied optics.

[14]  Michael S Feld,et al.  Optical fiber probe for biomedical Raman spectroscopy. , 2004, Applied optics.

[15]  T Joshua Pfefer,et al.  Selective detection of fluorophore layers in turbid media: the role of fiber-optic probe design. , 2003, Optics letters.

[16]  Janak Ramachandran,et al.  Light scattering and microarchitectural differences between tumorigenic and non-tumorigenic cell models of tissue. , 2007, Optics express.

[17]  Arjen Amelink,et al.  Optical spectroscopy for the classification of malignant lesions of the bronchial tree. , 2006, Chest.

[18]  K. Badizadegan,et al.  NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes. , 2002, Cancer research.

[19]  Wei Zheng,et al.  Beveled fiber-optic probe couples a ball lens for improving depth-resolved fluorescence measurements of layered tissue: Monte Carlo simulations , 2008, Physics in medicine and biology.

[20]  Irene Georgakoudi,et al.  Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo. , 2002, American journal of obstetrics and gynecology.

[21]  Arjen Amelink,et al.  Measurement of the local optical properties of turbid media by differential path-length spectroscopy. , 2004, Applied optics.

[22]  S. Shapshay,et al.  Detection of preinvasive cancer cells , 2000, Nature.

[23]  B Palcic,et al.  Optical properties of normal and carcinomatous bronchial tissue. , 1994, Applied optics.

[24]  R K Jain,et al.  Determinants of tumor blood flow: a review. , 1988, Cancer research.

[25]  B. Chance,et al.  Localization and kinetics of reduced pyridine nucleotide in living cells by microfluorometry. , 1959, The Journal of biological chemistry.

[26]  Mia K Markey,et al.  Probing local tissue changes in the oral cavity for early detection of cancer using oblique polarized reflectance spectroscopy: a pilot clinical trial. , 2008, Journal of biomedical optics.

[27]  B. Wilson,et al.  In Vivo Fluorescence Spectroscopy and Imaging for Oncological Applications , 1998, Photochemistry and photobiology.

[28]  R. Richards-Kortum,et al.  Fiber optic probes for biomedical optical spectroscopy. , 2003, Journal of biomedical optics.

[29]  Michele Follen,et al.  Sources of scattering in cervical tissue: determination of the scattering coefficient by confocal microscopy. , 2005, Applied optics.

[30]  T. Joshua Pfefer,et al.  Depth-sensitive reflectance measurements using obliquely oriented fiber probes , 2005, SPIE BiOS.

[31]  Rebecca Richards-Kortum,et al.  Autofluorescence and diffuse reflectance spectroscopy of oral epithelial tissue using a depth-sensitive fiber-optic probe. , 2008, Applied optics.

[32]  P. Friedl.  Dynamic imaging of cellular interactions with extracellular matrix , 2004, Histochemistry and Cell Biology.

[33]  Linda T. Nieman,et al.  Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance. , 2002, Journal of biomedical optics.

[34]  Rebecca Richards-Kortum,et al.  Determination of epithelial tissue scattering coefficient using confocal microscopy , 2003 .

[35]  Nirmala Ramanujam,et al.  Relationship between depth of a target in a turbid medium and fluorescence measured by a variable-aperture method. , 2002, Optics letters.

[36]  T Joshua Pfefer,et al.  Multiple-fiber probe design for fluorescence spectroscopy in tissue. , 2002, Applied optics.

[37]  Peter Carmeliet,et al.  VEGF as a Key Mediator of Angiogenesis in Cancer , 2005, Oncology.

[38]  Michele Follen,et al.  Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements. , 2004, Journal of biomedical optics.

[39]  P. Zigrino,et al.  Tumor-stroma interactions: their role in the control of tumor cell invasion. , 2005, Biochimie.

[40]  Judith R. Mourant,et al.  Light scattering from cells: the contribution of the nucleus and the effects of proliferative status , 2000 .

[41]  Michael S. Feld,et al.  Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ , 1999 .

[42]  L. Matrisian,et al.  Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. , 1996, The American journal of pathology.

[43]  Rebecca Richards-Kortum,et al.  Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial tissue. , 2005, Optics letters.

[44]  R. Richards-Kortum,et al.  Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition. , 2003, Journal of biomedical optics.

[45]  R Richards-Kortum,et al.  Reflectance spectroscopy with polarized light: is it sensitive to cellular and nuclear morphology. , 1999, Optics express.

[46]  Michele Follen,et al.  Autofluorescence Microscopy of Fresh Cervical‐Tissue Sections Reveals Alterations in Tissue Biochemistry with Dysplasia ¶ , 2001 .

[47]  Michael B. Wallace,et al.  Observation of periodic fine structure in reflectance from biological tissue: A new technique for measuring nuclear size distribution , 1998 .

[48]  Michele Follen,et al.  Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia. , 2006, Journal of biomedical optics.

[49]  R Richards-Kortum,et al.  Detection and diagnosis of oral neoplasia with an optical coherence microscope. , 2004, Journal of biomedical optics.

[50]  R. Richards-Kortum,et al.  Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture. , 2003, Journal of biomedical optics.

[51]  E. Sevick-Muraca,et al.  Quantitative optical spectroscopy for tissue diagnosis. , 1996, Annual review of physical chemistry.

[52]  Anant Agrawal,et al.  Oblique-incidence illumination and collection for depth-selective fluorescence spectroscopy. , 2005, Journal of biomedical optics.

[53]  Arjen Amelink,et al.  Optical biopsy of breast tissue using differential path-length spectroscopy , 2005, Physics in medicine and biology.

[54]  J Wu,et al.  Intrinsic fluorescence spectroscopy in turbid media: disentangling effects of scattering and absorption. , 2001, Applied optics.