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.

We report on imaging of microcirculation by calculating the speckle variance of optical coherence tomography (OCT) structural images acquired using a Fourier domain mode-locked swept-wavelength laser. The algorithm calculates interframe speckle variance in two-dimensional and three-dimensional OCT data sets and shows little dependence to the Doppler angle ranging from 75° to 90°. We demonstrate in vivo detection of blood flow in vessels as small as $25\mu \mathrm{m}$ in diameter in a dorsal skinfold window chamber model with direct comparison with intravital fluorescence confocal microscopy. This technique can visualize vessel-size-dependent vascular shutdown and transient vascular occlusion during Visudyne photodynamic therapy and may provide opportunities for studying therapeutic effects of antivascular treatments without on exogenous contrast agent.

Polarized light point measurements and wide-field imaging have been studied for many years in an effort to develop accurate and information-rich tissue diagnostic methods. However, the extensive depolarization of polarized light in thick biological tissues has limited the success of these investigations. Recently, advances in technology and conceptual understanding have led to a significant resurgence of research activity in the promising field of bulk tissue polarimetry. In particular, with the advent of improved measurement, analysis, and interpretation methods, including Mueller matrix decomposition, new diagnostic avenues, such as quantification of microstructural anisotropy in bulk tissues, have been enabled. Further, novel technologies have improved the speed and the accuracy of polarimetric instruments for ex vivo and in vivo diagnostics. In this paper, we review some of the recent progress in tissue polarimetry, provide illustrative application examples, and offer an outlook to the future of polarized light imaging in bulk biological tissues.

Linear birefringence and optical activity are two common optical polarization effects present in biological tissue, and determination of these properties has useful biomedical applications. However, 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 simultaneously. We have investigated the efficacy of a Mueller matrix decomposition methodology to extract the individual intrinsic polarimetry characteristics (linear retardance $δ$ and optical rotation $ψ$, in particular) from a multiply scattering medium exhibiting simultaneous linear birefringence and optical activity. In the experimental studies, a photoelastic 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 controlled polarization properties yielded reasonable estimates for $δ$ and $ψ$ parameters. The confounding effects of scattering, the propagation path of multiple scattered photons, and detection geometry on the estimated values for $δ$ and $ψ$ 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 $δ$ and $ψ$ with reasonable accuracy. The ability of this approach to extract the individual intrinsic polarimetry characteristics should prove valuable in diagnostic photomedicine, for example, in quantifying the small optical rotations due to the presence of glucose in tissue and for monitoring changes in tissue birefringence as a signature of tissue abnormality.

We optimize speckle variance optical coherence tomography (svOCT) imaging of microvasculature in high and low bulk tissue motion scenarios. To achieve a significant level of image contrast, frame rates must be optimized such that tissue displacement between frames is less than the beam radius. We demonstrate that higher accuracy estimates of speckle variance can enhance the detection of capillaries. These findings are illustrated in vivo by imaging the dorsal window chamber model (low bulk motion). We also show svOCT imaging of the nonstabilized finger (high bulk motion), using optimized imaging parameters, demonstrating better vessel detection than Doppler OCT.

Purpose: Optical coherence tomography (OCT) is an optical imaging method that can visualize cellular and extracellular structures at and below tissue surface. The objective of the study was to determine if OCT could characterize preneoplastic changes in the bronchial epithelium identified by autofluorescence bronchoscopy.Experimental Design: A 1.5-mm fiberoptic probe was inserted via a bronchoscope into the airways of 138 volunteer heavy smokers participating in a chemoprevention trial and 10 patients with lung cancer to evaluate areas that were found to be normal or abnormal on autofluorescence bronchoscopy. Radial scanning of the airways was done to generate OCT images in real time. Following OCT imaging, the same sites were biopsied for pathologic correlation.Results: A total of 281 OCT images and the corresponding bronchial biopsies were obtained. The histopathology of these areas includes 145 normal/hyperplasia, 61 metaplasia, 39 mild dysplasia, 10 moderate dysplasia, 6 severe dysplasia, 7 carcinoma in situ, and 13 invasive carcinomas. Quantitative measurement of the epithelial thickness showed that invasive carcinoma was significantly different than carcinoma in situ (P = 0.004) and dysplasia was significantly different than metaplasia or hyperplasia (P = 0.002). In addition, nuclei of the cells corresponding to histologic results became more discernible in lesions that were moderate dysplasia or worse compared with lower-grade lesions.Conclusion: Preliminary data suggest that autofluorescence bronchoscopy–guided OCT imaging of bronchial lesions is technically feasible. OCT may be a promising nonbiopsy tool for in vivo imaging of preneoplastic bronchial lesions to study their natural history and the effect of chemopreventive intervention.