Polarisation optics for biomedical and clinical applications: a review.

Many polarisation techniques have been harnessed for decades in biological and clinical research, each based upon measurement of the vectorial properties of light or the vectorial transformations imposed on light by objects. Various advanced vector measurement/sensing techniques, physical interpretation methods, and approaches to analyse biomedically relevant information have been developed and harnessed. In this review, we focus mainly on summarising methodologies and applications related to tissue polarimetry, with an emphasis on the adoption of the Stokes-Mueller formalism. Several recent breakthroughs, development trends, and potential multimodal uses in conjunction with other techniques are also presented. The primary goal of the review is to give the reader a general overview in the use of vectorial information that can be obtained by polarisation optics for applications in biomedical and clinical research.

Complex vectorial optics through gradient index lens cascades.

Graded index (GRIN) lenses are commonly used for compact imaging systems. It is not widely appreciated that the ion-exchange process that creates the rotationally symmetric GRIN lens index profile also causes a symmetric birefringence variation. This property is usually considered a nuisance, such that manufacturing processes are optimized to keep it to a minimum. Here, rather than avoiding this birefringence, we understand and harness it by using GRIN lenses in cascade with other optical components to enable extra functionality in commonplace GRIN lens systems. We show how birefringence in the GRIN cascades can generate vector vortex beams and foci, and how it can be used advantageously to improve axial resolution. Through using the birefringence for analysis, we show that the GRIN cascades form the basis of a new single-shot Müller matrix polarimeter with potential for endoscopic label-free cancer diagnostics. The versatility of these cascades opens up new technological directions.

Monitoring microstructural variations of fresh skeletal muscle tissues by Mueller matrix imaging.

Recently many attempts have been made for extracting the structural information of myofibrils as indicators for diseases of skeletal muscle. In this paper we adopt wide-field illumination and take the backscattering Mueller matrix images of bovine skeletal muscle tissues during the 24-hour experimental time after the animal's death. The 2D images of Mueller matrix elements and their frequency distribution histograms (FDHs) reveal rich qualitative information on the changes in the microstructures of the skeletal muscle. The temporal variations of the sample are quantitatively analyzed using two Mueller matrix transformation (MMT) parameters. The characteristic features of the temporal plots are attributed to the rigor mortis and proteolysis processes. For a deeper insight on the relationship between the features of the MMT parameters and the microstructures during the rigor mortis and proteolysis processes, Monte Carlo (MC) simulations are carried out based on sphere-cylinder birefringence model (SCBM). The good agreement between the experimental and MC simulated results show that the FDHs and MMT parameters can describe more clearly the characteristic microstructural features of skeletal muscle tissues. The techniques are useful for the characterization of physiological status of tissues, or quantitative assessment of meat qualities in food industry.

Division of focal plane polarimeter-based 3 × 4 Mueller matrix microscope: a potential tool for quick diagnosis of human carcinoma tissues.

A polarization microscope is a useful tool to reveal the optical anisotropic nature of a specimen and can provide abundant microstructural information about samples. We present a division of focal plane (DoFP) polarimeter-based polarization microscope capable of simultaneously measuring both the Stokes vector and the 3×4 Mueller matrix with an optimal polarization illumination scheme. The Mueller matrix images of unstained human carcinoma tissue slices show that the m24 and m34 elements can provide important information for pathological observations. The characteristic features of the m24 and m34 elements can be enhanced by polarization staining under illumination by a circularly polarized light. Hence, combined with a graphics processing unit acceleration algorithm, the DoFP polarization microscope is capable of real-time polarization imaging for potential quick clinical diagnoses of both standard and frozen slices of human carcinoma tissues.

Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues.

Today the increasing cancer incidence rate is becoming one of the biggest threats to human health.Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper,we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameter scan provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

Quantitatively differentiating microstructures of tissues by frequency distributions of Mueller matrix images.

We present a new way to extract characteristic features of the Mueller matrix images based on their frequency distributions and the central moments. We take the backscattering Mueller matrices of tissues with distinctive microstructures, and then analyze the frequency distribution histograms (FDHs) of all the matrix elements. For anisotropic skeletal muscle and isotropic liver tissues, we find that the shapes of the FDHs and their central moment parameters, i.e., variance, skewness, and kurtosis, are not sensitive to the sample orientation. Comparisons among different tissues further indicate that the frequency distributions of Mueller matrix elements and their corresponding central moments can be used as indicators for the characteristic microstructural features of tissues. A preliminary application to human cervical cancerous tissues shows that the distribution curves and central moment parameters may have the potential to give quantitative criteria for cancerous tissues detections.

Optimization of GRIN lens Stokes polarimeter.

In a recent study we reported on the gradient index (GRIN) lens Stokes polarimeter (GLP) [Opt. Lett.39, 2656 (2014)10.1364/OL.39.002656OPLEDP0146-9592]. With a simple architecture, this polarimeter can measure the state of polarization in a single shot. In this article, we present further studies for improving the performance of the GLP. Detailed discussions are presented on the optimization process of the GLP based on different choices of data from the CCD images. It is pointed out that many optimization techniques, although developed for other types of Stokes polarimeters, can also be applied to the GLP because the GRIN lens can traverse all possible retardance and fast axis modulations.

Characterizing microstructures of cancerous tissues using multispectral transformed Mueller matrix polarization parameters.

In this paper, we take the transmission 3 × 3 linear polarization Mueller matrix images of the unstained thin slices of human cervical and thyroid cancer tissues, and analyze their multispectral behavior using the Mueller matrix transformation (MMT) parameters. The experimental results show that for both cervical and thyroid cancerous tissues, the characteristic features of multispectral transmitted MMT parameters can be used to distinguish the normal and abnormal areas. Moreover, Monte Carlo simulations based on the sphere-cylinder birefringence model (SCBM) provide additional information of the relations between the characteristic spectral features of the MMT parameters and the microstructures of the tissues. Comparisons between the experimental and simulated data confirm that the contrast mechanism of the transmission MMT imaging for cancer detection is the breaking down of birefringent normal tissues for cervical cancer, or the formation of birefringent surrounding structures accompanying the inflammatory reaction for thyroid cancer. It is also testified that, the characteristic spectral features of polarization imaging techniques can provide more detailed microstructural information of tissues for diagnosis applications.

Differentiating characteristic microstructural features of cancerous tissues using Mueller matrix microscope.

Polarized light imaging can provide rich microstructural information of samples, and has been applied to the detections of various abnormal tissues. In this paper, we report a polarized light microscope based on Mueller matrix imaging by adding the polarization state generator and analyzer (PSG and PSA) to a commercial transmission optical microscope. The maximum errors for the absolute values of Mueller matrix elements are reduced to 0.01 after calibration. This Mueller matrix microscope has been used to examine human cervical and liver cancerous tissues with fibrosis. Images of the transformed Mueller matrix parameters provide quantitative assessment on the characteristic features of the pathological tissues. Contrast mechanism of the experimental results are backed up by Monte Carlo simulations based on the sphere-cylinder birefringence model, which reveal the relationship between the pathological features in the cancerous tissues at the cellular level and the polarization parameters. Both the experimental and simulated data indicate that the microscopic transformed Mueller matrix parameters can distinguish the breaking down of birefringent normal tissues for cervical cancer, or the formation of birefringent surrounding structures accompanying the inflammatory reaction for liver cancer. With its simple structure, fast measurement and high precision, polarized light microscope based on Mueller matrix shows a good diagnosis application prospect.

Linear polarization optimized Stokes polarimeter based on four-quadrant detector.

A four-quadrant detector (4QD) consists of four well-balanced detectors. We report on a Stokes polarimeter with optimal linear polarization measurements based on a 4QD. We turned the four intensity-detection channels into four polarization-analyzing channels by placing four polarizers and one quarter-wave plate in front of the individual detectors. An optimization method for the four polarization-analyzing channels is proposed to improve measurement accuracy. Considering applications in favor of linear polarization measurements instead of global optimization for all the possible states of polarization (SOP), we optimize the polarimeter first for the linear polarization components and then for the circular polarization component. The polarimeter is capable of simultaneous measurements of fast varying SOP with improved performance for the linear polarizations.

Single-shot spatially modulated Stokes polarimeter based on a GRIN lens.

A new polarimeter for the simultaneous measurement of all Stokes parameters in a single shot is presented. It consists of only a gradient index (GRIN) lens, a polarizer, an imaging lens, and a CCD, without mechanical movements, electrical signal modulation, or the division of amplitude components. This design takes advantage of the continuous spatial distributions of birefringence value and the fast axis direction of a GRIN lens and derives the state of polarization (SOP) of the incident beam from the characteristic patterns on the CCD images. Tests show that this polarimeter is very accurate even with low-resolution images. It is versatile and adapts to light sources of different wavelengths. It is also very stable, robust, low cost, and simple to use.