Combined Monte Carlo and finite-difference time-domain modeling for biophotonic analysis: implications on reflectance-based diagnosis of epithelial precancer.

Monte Carlo (MC) modeling of photon transport in tissues is generally performed using simplified functions that only approximate the angular scattering properties of tissue constituents. However, such approximations may not be sufficient for fully characterizing tissue scatterers such as cells. Finite-difference time-domain (FDTD) modeling provides a flexible approach to compute realistic tissue phase functions that describe probability of scattering at different angles. We describe a computational framework that combines MC and FDTD modeling, and allows random sampling of scattering directions from FDTD phase functions. We carry out simulations to assess the influence of incorporating realistic FDTD phase functions on modeling spectroscopic reflectance signals obtained from normal and precancerous epithelial tissues. Simulations employ various fiber optic probe designs to analyze the sensitivity of different probe geometries to FDTD-generated phase functions. Combined MC/FDTD modeling results indicate that the form of the phase function used is an important factor in determining the reflectance profile of tissues, and detected reflectance intensity can change up to approximately 30% when a realistic FDTD phase function is used instead of an approximating function. The results presented need to be taken into account when developing photon propagation models or implementing inverse algorithms to extract optical properties from measurements.

[1]  Thomas H Foster,et al.  Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling. , 2005, Biophysical journal.

[2]  Allen Taflove,et al.  Computational Electrodynamics the Finite-Difference Time-Domain Method , 1995 .

[3]  Judith R Mourant,et al.  In vivo light scattering measurements for detection of precancerous conditions of the cervix. , 2007, Gynecologic oncology.

[4]  Edouard Berrocal,et al.  Laser light scattering in turbid media Part I: Experimental and simulated results for the spatial intensity distribution. , 2007, Optics express.

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

[6]  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.

[7]  Melissa C Skala,et al.  Investigation of fiber‐optic probe designs for optical spectroscopic diagnosis of epithelial pre‐cancers , 2004, Lasers in surgery and medicine.

[8]  L. Koss Diagnostic cytology and its histopathologic bases , 1968 .

[9]  Nitish V Thakor,et al.  Calcium-induced alterations in mitochondrial morphology quantified in situ with optical scatter imaging. , 2002, Biophysical journal.

[10]  C. Capjack,et al.  3-D simulation of light scattering from biological cells and cell differentiation. , 2005, Journal of biomedical optics.

[11]  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.

[12]  Andrew K. Dunn,et al.  Three-dimensional computation of light scattering from cells , 1996 .

[13]  J P Freyer,et al.  Angular dependent light scattering from multicellular spheroids. , 2002, Journal of biomedical optics.

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

[15]  Thomas H Foster,et al.  Index-of-refraction-dependent subcellular light scattering observed with organelle-specific dyes. , 2007, Journal of biomedical optics.

[16]  Rebekah Drezek,et al.  Targeting spectral signatures of progressively dysplastic stratified epithelia using angularly variable fiber geometry in reflectance Monte Carlo simulations. , 2007, Journal of biomedical optics.

[17]  Christian Depeursinge,et al.  In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties. , 2003, Journal of biomedical optics.

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

[19]  A. Dunn,et al.  Light scattering from cells: finite-difference time-domain simulations and goniometric measurements. , 1999, Applied optics.

[20]  A. Taflove,et al.  Recent progress in exact and reduced-order modeling of light-scattering properties of complex structures , 2005, IEEE Journal of Selected Topics in Quantum Electronics.

[21]  A H Hielscher,et al.  Influence of the scattering phase function on light transport measurements in turbid media performed with small source-detector separations. , 1996, Optics letters.

[22]  Leopold G. Koss,et al.  Kosss diagnostic cytology and its histopathologic bases , 2017 .

[23]  Xin-Hua Hu,et al.  Effect of detailed cell structure on light scattering distribution: FDTD study of a B-cell with 3D structure constructed from confocal images , 2006 .

[24]  Norman S. Nishioka,et al.  Light propagation in tissue during fluorescence spectroscopy with single-fiber probes , 2001 .

[25]  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.

[26]  Stefan Andersson-Engels,et al.  Fluorescence spectra provide information on the depth of fluorescent lesions in tissue. , 2005, Applied optics.

[27]  D T Delpy,et al.  Comment on 'the use of the Henyey-Greenstein phase function in Monte Carlo simulations in biomedical optics'. , 2006, Physics in medicine and biology.

[28]  Rebekah Drezek,et al.  Experimental evaluation of angularly variable fiber geometry for targeting depth-resolved reflectance from layered epithelial tissue phantoms. , 2007, Journal of biomedical optics.

[29]  M S Patterson,et al.  Total attenuation coefficients and scattering phase functions of tissues and phantom materials at 633 nm. , 1987, Medical physics.

[30]  Brian Cairns,et al.  Multiple scattering by random particulate media: exact 3D results. , 2007, Optics express.

[31]  R H Smallwood,et al.  A study of the morphological parameters of cervical squamous epithelium. , 2003, Physiological measurement.

[32]  J M Schmitt,et al.  Turbulent nature of refractive-index variations in biological tissue. , 1996, Optics letters.

[33]  R Richards-Kortum,et al.  Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications. , 2001, Journal of biomedical optics.

[34]  T. Kitai,et al.  Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical approach. , 1994, Biophysical journal.

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

[36]  L Wang,et al.  MCML--Monte Carlo modeling of light transport in multi-layered tissues. , 1995, Computer methods and programs in biomedicine.

[37]  D T Delpy,et al.  The use of the Henyey–Greenstein phase function in Monte Carlo simulations in biomedical optics , 2006, Physics in medicine and biology.

[38]  Michele Follen,et al.  Spatially resolved reflectance spectroscopy for diagnosis of cervical precancer: Monte Carlo modeling and comparison to clinical measurements. , 2006, Journal of biomedical optics.

[39]  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.

[40]  Nirmala Ramanujam,et al.  Use of a multiseparation fiber optic probe for the optical diagnosis of breast cancer. , 2005, Journal of biomedical optics.

[41]  R R Alfano,et al.  Fractal mechanisms of light scattering in biological tissue and cells. , 2005, Optics letters.

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

[43]  Melinda Piket-May,et al.  9 – Computational Electromagnetics: The Finite-Difference Time-Domain Method , 2005 .

[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]  C. Depeursinge,et al.  Monte Carlo study of diffuse reflectance at source–detector separations close to one transport mean free path , 1999 .

[46]  R Richards-Kortum,et al.  A pulsed finite-difference time-domain (FDTD) method for calculating light scattering from biological cells over broad wavelength ranges. , 2000, Optics express.

[47]  S. J. Matcher,et al.  Computer simulation of the skin reflectance spectra , 2003, Comput. Methods Programs Biomed..

[48]  Džena Hidović-Rowe,et al.  Modelling and validation of spectral reflectance for the colon , 2005, Physics in medicine and biology.

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

[50]  Ying Liu,et al.  Influence of the third-order parameter on diffuse reflectance at small source-detector separations. , 2006, Optics letters.

[51]  Stefan Andersson-Engels,et al.  Light scattering by multiple red blood cells. , 2004, Journal of the Optical Society of America. A, Optics, image science, and vision.

[52]  P. B. Cipolloni,et al.  Noninvasive sizing of subcellular organelles with light scattering spectroscopy , 2003 .

[53]  R Hibst,et al.  Influence of the phase function on determination of the optical properties of biological tissue by spatially resolved reflectance. , 2001, Optics letters.

[54]  J. Mourant,et al.  High-angle scattering events strongly affect light collection in clinically relevant measurement geometries for light transport through tissue. , 2000, Physics in medicine and biology.