Polarimetry has a long and successful history in various forms of clear media. Driven by their biomedical potential, the use of the polarimetric approaches for biological tissue assessment has also recently received considerable attention. Specifically, polarization can be used as an effective tool to discriminate against multiply scattered light (acting as a gating mechanism) in order to enhance contrast and to improve tissue imaging resolution. Moreover, the intrinsic tissue polarimetry characteristics contain a wealth of morphological and functional information of potential biomedical importance. However, in a complex random medium-like tissue, numerous complexities due to multiple scattering and simultaneous occurrences of many scattering and polarization events present formidable challenges both in terms of accurate measurements and in terms of analysis of the tissue polarimetry signal. In order to realize the potential of the polarimetric approaches for tissue imaging and characterization/diagnosis, a number of researchers are thus pursuing innovative solutions to these challenges. In this review paper, we summarize these and other issues pertinent to the polarized light methodologies in tissues. Specifically, we discuss polarized light basics, Stokes-Muller formalism, methods of polarization measurements, polarized light modeling in turbid media, applications to tissue imaging, inverse analysis for polarimetric results quantification, applications to quantitative tissue assessment, etc.

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Tissue polarimetry: concepts, challenges, applications, and outlook

Surface-enhanced Raman scattering (SERS) spectroscopy provides a noninvasive and highly sensitive route for fingerprint and label-free detection of a wide range of molecules. Recently, flexible SERS has attracted increasingly tremendous research interest due to its unique advantages compared to rigid substrate-based SERS. Here, the latest advances in flexible substrate-based SERS diagnostic devices are investigated in-depth. First, the intriguing prospect of point-of-care diagnostics is briefly described, followed by an introduction to the cutting-edge SERS technique. Then, the focus is moved from conventional rigid substrate-based SERS to the emerging flexible SERS technique. The main part of this report highlights the recent three categories of flexible SERS substrates, including actively tunable SERS, swab-sampling strategy, and the in situ SERS detection approach. Furthermore, other promising means of flexible SERS are also introduced. The flexible SERS substrates with low-cost, batch-fabrication, and easy-to-operate characteristics can be integrated into portable Raman spectroscopes for point-of-care diagnostics, which are conceivable to penetrate global markets and households as next-generation wearable sensors in the near future.

https://www.onlinelibrary.wiley.com/doi/epdf/10.1002/advs.201900925

Toward Flexible Surface-Enhanced Raman Scattering (SERS) Sensors for Point-of-Care Diagnostics

An objective analysis is carried out of the matricial models representing the polarimetric properties of light and material media leading to the identification and definition of their corresponding physical quantities, using the concept of the coherency matrix. For light, cases of homogeneous and inhomogeneous wavefront are analyzed, and a model for 3D polarimetric purity is constructed. For linear passive material media, a general model is developed on the basis that any physically realizable linear transformation of Stokes vectors is equivalent to an ensemble average of passive, deterministic nondepolarizing transformations. Through this framework, the relevant physical quantities, including indices of polarimetric purity, are identified and decoupled. Some decompositions of the whole system into a set of well-defined components are considered, as well as techniques for isolating the unknown components by means of new procedures for subtracting coherency matrices. These results and methods constitute a powerful tool for analyzing and exploiting experimental and industrial polarimetry. Some particular application examples are indicated.

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Polarimetric characterization of light and media - Physical quantities involved in polarimetric phenomena

Linear birefringence and optical activity are two common optical polarization effects present in biological tissue, and determi- nation of these properties has useful biomedical applications. How- ever, measurement and unique interpretation of these parameters in tissue is hindered by strong multiple scattering effects and by the fact that these and other polarization effects are often present simulta- neously. We have investigated the efficacy of a Mueller matrix decom- position methodology to extract the individual intrinsic polarimetry characteristics linear retardance and optical rotation , in particu- lar from a multiply scattering medium exhibiting simultaneous linear birefringence and optical activity. In the experimental studies, a pho- toelastic modulation polarimeter was used to record Mueller matrices from polyacrylamide phantoms having strain-induced birefringence, sucrose-induced optical activity, and polystyrene microspheres- induced scattering. Decomposition of the Mueller matrices recorded in the forward detection geometry from these phantoms with con- trolled polarization properties yielded reasonable estimates for and parameters. The confounding effects of scattering, the propagation path of multiple scattered photons, and detection geometry on the estimated values for and were further investigated using polarization-sensitive Monte Carlo simulations. The results show that in the forward detection geometry, the effects of scattering induced linear retardance and diattenuation are weak, and the decomposition of the Mueller matrix can retrieve the intrinsic values for and with reasonable accuracy. The ability of this approach to extract the indi- vidual intrinsic polarimetry characteristics should prove valuable in diagnostic photomedicine, for example, in quantifying the small opti- cal rotations due to the presence of glucose in tissue and for monitor- ing changes in tissue birefringence as a signature of tissue abnormality. © 2008 Society of Photo-Optical Instrumentation Engineers. DOI: 10.1117/1.2960934

http://wwwlabs.uhnresearch.ca/biophotonics/staff_papers/vitkin/2008/2008-JBO-Wood-MullerMatrix.pdf

Mueller matrix decomposition for extraction of individual polarization parameters from complex turbid media exhibiting multiple scattering, optical activity, and linear birefringence

This tutorial-review introduces the fundamentals of polarized light interaction with biological tissues and presents some of the recent key polarization optical methods that have made possible the quantitative studies essential for biomedical diagnostics. Tissue structures and the corresponding models showing linear and circular birefringence, dichroism, and chirality are analyzed. As the basis for a quantitative description of the interaction of polarized light with tissues, the theory of polarization transfer in a random medium is used. This theory employs the modified transfer equation for Stokes parameters to predict the polarization properties of single- and multiple-scattered optical fields. The near-order of scatterers in tissues is accounted for to provide an adequate description of tissue polarization properties. Biomedical diagnostic techniques based on polarized light detection, including polarization imaging and spectroscopy, amplitude and intensity light scattering matrix measurements, and polarization-sensitive optical coherence tomography are described. Examples of biomedical applications of these techniques for early diagnostics of cataracts, detection of precancer, and prediction of skin disease are presented. The substantial reduction of light scattering multiplicity at tissue optical clearing that leads to a lesser influence of scattering on the measured intrinsic polarization properties of the tissue and allows for more precise quantification of these properties is demonstrated.

https://www.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-21/issue-7/071114/Polarized-light-interaction-with-tissues/10.1117/1.JBO.21.7.071114.pdf

Polarized light interaction with tissues

For in vivo determination of optically active (chiral) substances in turbid media, like for example glucose in human tissue, the backscattering geometry is particularly convenient. However, recent polarimetric measurements performed in the backscattering geometry have shown that, in this geometry, the relatively small rotation of the polarization vector arising due to the optical activity of the medium is totally swamped by the much larger changes in the orientation angle of the polarization vector due to scattering. We show that the change in the orientation angle of the polarization vector arises due to the combined effect of linear diattenuation and linear retardance of light scattered at large angles and can be decoupled from the pure optical rotation component using polar decomposition of Mueller matrix. For this purpose, the method developed earlier for polar decomposition of Mueller matrix was extended to incorporate optical rotation in the medium. The validity of this approach for accurate determination of the degree of optical rotation using the Mueller matrix measured from the medium in both forward and backscattering geometry was tested by conducting studies on chiral turbid samples prepared using known concentration of scatterers and glucose molecules.

Mueller matrix approach for determination of optical rotation in chiral turbid media in backscattering geometry.

Energy of the indirect and direct optical bandgap of near-stoichiometric lithium niobate (nSLN) crystals is evaluated by optical absorption measurement. The value of the indirect bandgap (3.95 eV) is consistent with the earlier reports. However, the direct bandgap energy of 4.12 eV is higher than the previously reported experimental value (3.68 eV). The direct bandgap energy obtained here is closer to the recent theoretical value estimated by Thierfelder et al. [Phys. Status Solidi C 7, 362 (2010)] in comparison to the previously predicted value by Ching et al. [Phys. Rev. B 50, 1992 (1994)]. The phonons involved in the indirect allowed transitions have energies ∼85 meV (685 cm−1) and are identified as the E(TO9) and E(LO8) optical phonon modes from the Raman scattering measurement.

Urbach tail and bandgap analysis in near stoichiometric LiNbO3 crystals

The polarization properties of any medium are completely described by the sixteen element Mueller matrix that relates the polarization parameters of the light incident on the medium to that emerging from it. Measurement of all the elements of the matrix requires a minimum of sixteen measurements involving both linear and circularly polarized light. However, for many diagnostic applications, it would be useful if the polarization parameters can be quantified with linear polarization measurements alone. In this paper, we present a method based on polar decomposition of Mueller matrix for quantification of the polarization parameters of a scattering medium using the nine element (3 x 3) Mueller matrix that requires linear polarization measurements only. The methodology for decomposition of the 3 x 3 Mueller matrix is based on the previously developed decomposition process for sixteen element (4 x 4) Mueller matrix but with an assumption that the depolarization of linearly polarized light due to scattering is independent of the orientation angle of the incident linear polarization vector. Studies conducted on various scattering samples demonstrated that this assumption is valid for a turbid medium like biological tissue where the depolarization of linearly polarized light primarily arises due to the randomization of the field vector's direction as a result of multiple scattering. For such medium, polar decomposition of 3 x 3 Mueller matrix can be used to quantify the four independent polarization parameters namely, the linear retardance (delta ), the circular retardance (psi), the linear depolarization coefficient (Delta) and the linear diattenuation (d) with reasonable accuracy. Since this approach requires measurements using linear polarizers only, it considerably simplifies measurement procedure and might find useful applications in tissue diagnosis using the retrieved polarization parameters.

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Polar decomposition of 3 x 3 Mueller matrix: a tool for quantitative tissue polarimetry.

Conversion of 3×3 Mueller matrix to 4×4 Mueller matrix for non-depolarizing samples

Most early cancers arise in epithelial tissue and areassociated with alterations in both epithelial cellsand stroma [1–7]. Since collagen fibers, the mainscatterers in the stroma underlying the epithelium,are birefringent it is expected that neoplasticchanges would lead to changes in the polarizationparameters (retardance, diattenuation and depolari-zation) of the tissue. By measurement of the Muellermatrix of the tissue, and its polar decomposition[8, 9], the polarization parameters of the tissue canbe extracted and used for diagnostic applications.This approach has been investigated for the diagno-sis of oral and skin cancer [4–7]. The results of thesestudies have confirmed that the normal to malignant

M. K. Swami

Papers

Mueller matrix approach for determination of optical rotation in chiral turbid media in backscattering geometry.

Urbach tail and bandgap analysis in near stoichiometric LiNbO3 crystals

Polar decomposition of 3 x 3 Mueller matrix: a tool for quantitative tissue polarimetry.

Conversion of 3×3 Mueller matrix to 4×4 Mueller matrix for non-depolarizing samples

Polarized diffuse reflectance measurements on cancerous and noncancerous tissues