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.
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.
Stereotactic body radiotherapy (SBRT) is an emerging cancer treatment due to its logistical and potential therapeutic benefits as compared to conventional radiotherapy. However, its mechanism of ...action is yet to be fully understood, likely involving the ablation of tumour microvasculature by higher doses per fraction used in SBRT. In this study, we hypothesized that longitudinal imaging and quantification of the vascular architecture may elucidate the relationship between the microvasculature and tumour response kinetics. Pancreatic human tumour xenografts were thus irradiated with single doses of Formula: see text, Formula: see text and Formula: see text Gy to simulate the first fraction of a SBRT protocol. Tumour microvascular changes were monitored with optical coherence angiography for up to Formula: see text weeks following irradiation. The temporal kinetics of two microvascular architectural metrics were studied as a function of time and dose: the diffusion-limited fraction, representing poorly vascularized tissue Formula: see text μm from the nearest detected vessel, and the vascular distribution convexity index, a measure of vessel aggregation at short distances. These biological metrics allowed for dose dependent temporal evaluation of tissue (re)vascularization and vessel aggregation after radiotherapy, showing promise for determining the SBRT dose-response relationship.
A new polarimetry method is demonstrated to image the entire Mueller matrix of a turbid sample using four photoelastic modulators (PEMs) and a charge coupled device (CCD) camera, with no moving ...parts. Accurate wide-field imaging is enabled with a field-programmable gate array (FPGA) optical gating technique and an evolutionary algorithm (EA) that optimizes imaging times. This technique accurately and rapidly measured the Mueller matrices of air, polarization elements, and turbid phantoms. The system should prove advantageous for Mueller matrix analysis of turbid samples (e.g., biological tissues) over large fields of view, in less than a second.
The effects of scatterer size and scattering coefficient on backscattered linearly and circularly polarized light are investigated through Stokes polarimetry. High-SNR polarization ...modulation/synchronous detection measurements are corroborated by polarization-sensitive Monte Carlo simulations. Circular degree of polarization (DOP) is found to be sensitive to scatterer size, but is equivocal at times due to helicity flipping effects; linear DOP appears to be mostly dependent on the medium scattering coefficient. We exploit these trends to generate a DOP
C
- DOP
L
response surface which clusters turbid samples based on these medium properties. This work may prove useful in biomedicine, for example in noninvasive assessment of epithelial precancer progression.
Plasmonic gold nanorods (GNRs) are finding increasing use in biomedicine due to their unique electromagnetic properties, optical contrast enhancement and biocompatibility; they also show promise as ...polarization contrast agents. However, quantification of their polarization-enhancing properties within heterogeneous turbid media remains challenging. We report on polarization response in controlled tissue phantoms consisting of dielectric microsphere scatterers with varying admixtures of GRNs. Experimental Mueller matrix measurements and polarization sensitive Monte-Carlo simulations show excellent agreement. Despite the GNRs' 3D random orientation and distribution in the strong multiply scattering background, significant linear diattenuation and retardance were observed. These exclusive measurable characteristics of GNRs suggest their potential uses as contrast enhancers for polarimetric assessment of turbid biological tissue.
Backscattered circularly polarized light from turbid media consists of helicity-flipped and helicity-preserved photon sub-populations (i.e., photons of perpendicular and parallel circular ...handedness). Their intensities and spatial distributions are found to be acutely sensitive to average scatterer size and modestly sensitive to the scattering coefficient (medium turbidity) through an interplay of single and multiple scattering effects. Using a highly sensitive intensified-CCD camera, helicity-based images of backscattered light are captured, which, with the aid of corroborating Monte Carlo simulation images and statistics, enable (1) investigation of subsurface photonic pathways and (2) development of the novel 'spatial helicity response' metric to quantify average scatterer size and turbidity of tissue-like samples. An exciting potential application of this work is noninvasive early cancer detection since malignant tissues exhibit alterations in scatterer size (larger nuclei) and turbidity (increased cell density).
Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is emerging as a valuable tool for non-invasive volumetric monitoring of the tumor vascular status and its therapeutic response. ...However, clinical utility of DCE-MRI is challenged by uncertainty in its ability to quantify the tumor microvasculature (Formula: see text scale) given its relatively poor spatial resolution (mm scale at best). To address this challenge, we directly compared DCE-MRI parameter maps with co-registered micron-scale-resolution speckle variance optical coherence tomography (svOCT) microvascular images in a window chamber tumor mouse model. Both semi and fully quantitative (Toft's model) DCE-MRI metrics were tested for correlation with microvascular svOCT biomarkers. svOCT's derived vascular volume fraction (VVF) and the mean distance to nearest vessel (Formula: see text) metrics were correlated with DCE-MRI vascular biomarkers such as time to peak contrast enhancement (Formula: see text and Formula: see text respectively, Formula: see text for both), the area under the gadolinium-time concentration curve (Formula: see text and Formula: see text respectively, Formula: see text for both) and Formula: see text (Formula: see text and Formula: see text respectively, Formula: see text for both). Several other correlated micro-macro vascular metric pairs were also noted. The microvascular insights afforded by svOCT may help improve the clinical utility of DCE-MRI for tissue functional status assessment and therapeutic response monitoring applications.
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 degrees to 90 degrees . We demonstrate in vivo detection of blood flow in vessels as small as 25 microm 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.
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
and optical rotation
, 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
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 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.
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