Jones-matrix imaging of biological tissues with quadruple-channel optical coherence tomography

Two-dimensional depth-resolved Jones-matrix images of scattering biological tissues were measured with novel double-source double-detector polarization-sensitive optical coherence tomography (OCT). The Jones matrix can be determined in a single scan with this OCT system. The experimental results show that this system can be effectively applied to the measurement of soft tissues, which are less stable than hard tissues. Polarization parameters such as diattenuation, birefringence, and orientation of the fast axis can be extracted through decomposition of the measured Jones matrix. The Jones matrix of thermally treated porcine tendon showed a reduction of birefringence from thermal damage. The Jones matrices of porcine skin and bovine cartilage also revealed that the density and orientation of the collagen fibers in porcine skin and bovine cartilage are not distributed as uniformly as in porcine tendon. Birefringence is sensitive to changes in tissue because it is based on phase contrast

Measuring Collagen Arrangement and Its Relationship with Preterm Birth using Mueller Matrix Polarimetry

Preterm birth (PTB) is defined as delivery prior to 37 weeks of gestation. It is the leading cause of infant death worldwide, responsible for infant neurological disorders, long-term cognitive impairment, as well as chronic health issues involving the auditory, visual, digestive, and respiratory systems. In expectant mothers, causes for PTB can include infection, inflammation, vascular disease, short intervals between pregnancies, multiple gestations and genetic factors. In the U.S., PTB occurs in over 11% of births and at an elevated 18.1% in Miami-Dade County, FL; while in the developing world the incidence of PB is over 15%. Early identification of at-risk pregnancies is important for the success of medical intervention. Current diagnosis methodologies of PTB include ultrasound imaging of cervical length and fetal fibronectin assay but have low positive predictive power. Compared to the markers targeted by current diagnosis methodologies, collagen content in the cervix changes more drastically throughout the course of gestation due to its link to changes in load bearing capacity that occur during the phases of pregnancy. Mueller matrix polarimetry is capable of characterizing changes in collagen without making contact with patients and may prove to be an improvement to current diagnosis methodologies. A clear difference is seen in collagen orientation between nonpregnant and pregnant patients. The development of a new imaging modality aimed at assessing early changes in collagen arrangement in the cervix may improve risk determination of PTB and reduce the morbidity of the condition. Earlier prediction of PTB could improve outcomes by allowing longer intervention times to prolong gestation time for the infant in the womb. A more reliable quantitative predictor may also lead to development of more treatment options

Optical tracking of nerve activity using intrinsic changes in birefringence

Changes in birefringence (or dynamic birefringence) provide an arguably cleaner method of measuring IOS as compared to scattering methods. Other imaging methods have substantial limitations. Nerves inherently exhibit a static (rest condition) birefringence that is associated with the structural anisotropies of axonal protein filaments, membrane phospholipids and proteins, as well as surrounding tissues, which include Schwann cells and axon sheaths. The dynamic birefringence, or “crossed-polarized signal” (XPS), in neurons arises from activity in axons and occurs with a rapid momentary change, typically a decrease, in the birefringence when action potentials (APs) propagate along them. We improved the signal-to-noise to make detecting this signal an easier task, and present the XPS as a viable candidate for detecting AP activity in anisotropic nervous tissue. Our data collectively serves as a strong indication that there is a capacitive-charging-like effect directly inducing a gradual recovery (long tail) of the XPS to baseline, and also causing a smoothing of the XPS trace. A setup was constructed that successfully demonstrated the feasibility of tracking propagating compound APs in a peripheral nerve using the XPS. We made significant progress in the attempt to investigate birefringence of myelination. For the first time, the XPS in a myelinated tissue was detected, and it appears to be bipolar in nature. Further work in investigating the nature of this signal is needed, and is currently underway. Since changes in birefringence in neurons are associated instantaneously with electrophysiological phenomena, they are well-suited for fast imaging of propagating action potentials in neuronal tissue. In summary, imaging based on polarization sensing of changes in birefringence offers promise for an improved noninvasive method of detecting and tracking AP activity in myelinated and unmyelinated nerves and could be designed for pre-clinical and surgical applications

Polarization Sensor Design for Biomedical Applications

Advances in fabrication technology have enabled the development of compact, rigid polarization image sensors by integrating pixelated polarization filters with standard image sensing arrays. These compact sensors have the capability for allowing new applications across a variety of disciplines, however their design and use may be influenced by many factors. The underlying image sensor, the pixelated polarization filters, and the incident lighting conditions all directly impact how the sensor performs. In this research endeavor, I illustrate how a complete understanding of these factors can lead to both new technologies and applications in polarization sensing. To investigate the performance of the underlying image sensor, I present a new CMOS image sensor architecture with a pixel capable of operation using either measured voltages or currents. I show a detailed noise analysis of both modes, and that, as designed, voltage mode operates with lower noise than current mode. Further, I integrated aluminum nanowires with this sensor post fabrication, realizing the design of a compact CMOS sensor with polarization sensitivity. I describe a full set of experiments designed as a benchmark to evaluate the performance of compact, integrated polarization sensors. I use these tests to evaluate for incident intensity, wavelength, focus, and polarization state, demonstrating the accuracy and limitations of polarization measurements with such a compact sensor. Using these as guides, I present two novel biomedical applications that rely on the compact, real-time nature of compact integrated polarimeters. I first demonstrate how these sensors can be used to measure the dynamics of soft tissue in real-time, with no moving parts or complex optical alignment. I used a 2 megapixel integrated polarization sensor to measure the direction and strength of alignment in a bovine flexor tendon at over 20 frames per second, with results that match the current method of rotating polarizers. Secondly, I present a new technique for optical neural recording that uses intrinsic polarization reflectance and requires no fluorescent dyes or electrodes. Exposing the antennal lobe of the locust Schistocerca americana, I was able to measure a change in the polarization reflectance during the introduction of the odors hexanol and octanol with the integrated CMOS polarization sensor

Fiber Optic Sensors and Fiber Lasers

The optical fiber industry is emerging from the market for selling simple accessories using optical fiber to the new optical-IT convergence sensor market combined with high value-added smart industries such as the bio industry. Among them, fiber optic sensors and fiber lasers are growing faster and more accurately by utilizing fiber optics in various fields such as shipbuilding, construction, energy, military, railway, security, and medical.This Special Issue aims to present novel and innovative applications of sensors and devices based on fiber optic sensors and fiber lasers, and covers a wide range of applications of optical sensors. In this Special Issue, original research articles, as well as reviews, have been published

Design and development of optical reflectance spectroscopy and optical coherence tomography catheters for myocardial tissue characterization

Catheter ablation therapy attempts to restore sinus rhythm in arrhythmia patients by producing site-specific tissue modification along regions which cause abnormal electrical activity. This treatment, though widely used, often requires repeat procedures to observe long-term therapeutic benefits. This limitation is driven in part by challenges faced by conventional schemes in validating lesion adequacy at the time of the procedure. Optical techniques are well-suited for the interrogation and characterization of biological tissues. In particular, optical coherence tomography (OCT) relies on coherence gating of singly-scattered light to enable high-resolution structural imaging for tissue diagnostics and procedural guidance. Alternatively, optical reflectance spectroscopy (ORS) is a point measurement technique which makes use of incoherent, multiply-scattered light to probe tissue volumes and derive important data from its optical signature. ORS relies on the fact that light-tissue interactions are regulated by absorption and scattering, which directly relate to the intrinsic tissue biochemistry and cellular organization. In this thesis, we explore the integration of these modalities into ablation catheters for obtaining procedural metrics which could be utilized to guide catheter ablation therapy. We first present the development of an accelerated computational light transport model and its application for guiding ORS catheter design. A custom ORS-integrated ablation catheter is then implemented and tested within porcine specimens in vitro. A model is proposed for real-time estimation of lesion size based on changes in spectral morphology acquired during ablation. We then fabricated custom integrated OCT M-mode RF catheters and present a model for detecting contact status based on deep convolutional neural networks trained on endomyocardial images. Additionally, we demonstrate for the first time, tracking of RF-induced lesion formation employing OCT Doppler micro-velocimetry; this response is shown to be commensurate with the degree of treatment. We further demonstrate for the first time spectroscopic tracking of kinetics related to the heme oxidation cascade during thermal treatment, which are linked to tissue denaturation. The pairing of these modalities into a single RF catheter was also validated for guiding lesion delivery in vitro and within live pigs. Finally, we conclude with a proof-of-concept demonstration of ORS as a mapping tool to guide epicardial ablation in human donor hearts. These results showcase the vast potential of ORS and OCT empowered RF catheters for aiding intraprocedural guidance of catheter ablation procedures which could be utilized alongside current practices

Development of polarization-resolved optical scanning microscopy imaging techniques to study biomolecular organizations

Light, as electromagnetic radiation, conveys energy through space and time via fluctuations in electric and magnetic fields. This thesis explores the interaction of light and biological structures through polarization-resolved imaging techniques. Light microscopy, and polarization analysis enable the examination of biological entities. Biological function often centers on chromatin, the genetic material composed of DNA wrapped around histone proteins within cell nuclei. This structure's chiral nature gives rise to interactions with polarized light. This research encompasses three main aspects. Firstly, an existing multimodal Circular Intensity Differential Scattering (CIDS) and fluorescence microscopy are upgraded into an open configuration to be integrated with other modalities. Secondly, a novel cell classification method employing CIDS and a phasor representation is introduced. Thirdly, polarization analysis of fluorescence emission is employed for pathological investigations. Accordingly, the thesis is organized into three chapters. Chapter 1 lays the theoretical foundation for light propagation and polarization, outlining the Jones and Stokes-Mueller formalisms. The interaction between light and optical elements, transmission, and reflection processes are discussed. Polarized light's ability to reveal image contrast in polarizing microscopes, linear and nonlinear polarization-resolved microscopy, and Mueller matrix microscopy as a comprehensive technique for studying biological structures are detailed. Chapter 2 focuses on CIDS, a label-free light scattering method, including a single point angular spectroscopy mode and scanning microscopy imaging. A significant upgrade of the setup is achieved, incorporating automation, calibration, and statistical analysis routines. An intuitive phasor approach is proposed, enabling image segmentation, cell discrimination, and enhanced interpretation of polarimetric contrast. As a result, image processing programs have been developed to provide automated measurements using polarization-resolved laser scanning microscopy imaging integrated with confocal fluorescence microscopy of cells and chromatin inside cell nuclei, including the use of new types of samples such as progeria cells. Chapter 3 applies a polarization-resolved two-photon excitation fluorescence (2PEF) microscopy to study multicellular cancerous cells. A homemade 2PEF microscope is developed for colon cancer cell analysis. The integration of polarization and fluorescence techniques leads to a comprehensive understanding of the molecular orientation within samples, particularly useful for cancer diagnosis. Overall, this thesis presents an exploration of polarization-resolved imaging techniques for studying biological structures, encompassing theory, experimental enhancements, innovative methodologies, and practical applications

Single-pulse, Kerr-effect Mueller Matrix LiDAR Polarimeter

We present a novel light detection and ranging (LiDAR) polarimeter that enables measurement of 12 of 16 sample Mueller matrix elements in a single, 10 ns pulse. The new polarization state generator (PSG) leverages Kerr phase modulation in a birefringent optical fiber, creating a probe pulse characterized by temporally varying polarization. Theoretical expressions for the Polarization State Generator (PSG) Stokes vector are derived for birefringent walk-off and no walk-off and incorporated into a time-dependent polarimeter signal model employing multiple polarization state analyzers (PSA). Polarimeter modeling compares the Kerr effect and electro-optic phase modulator–based PSG using a single Polarization State Analyzer (PSA) and a scattering sample yielding similarly good performance for both. We include results from an experimental demonstration of the Kerr effect PSG

A dual-modality imaging method based on polarimetry and second harmonic generation for characterization and evaluation of skin tissue structures

The characterization and evaluation of skin tissue structures are crucial for dermatological applications. Recently, Mueller matrix polarimetry and second harmonic generation microscopy have been widely used in skin tissue imaging due to their unique advantages. However, the features of layered skin tissue structures are too complicated to use a single imaging modality for achieving a comprehensive evaluation. In this study, we propose a dual-modality imaging method combining Mueller matrix polarimetry and second harmonic generation microscopy for quantitative characterization of skin tissue structures. It is demonstrated that the dual-modality method can well divide the mouse tail skin tissue specimens' images into three layers of stratum corneum, epidermis, and dermis. Then, to quantitatively analyze the structural features of different skin layers, the gray level co-occurrence matrix is adopted to provide various evaluating parameters after the image segmentations. Finally, to quantitatively measure the structural differences between damaged and normal skin areas, an index named Q-Health is defined based on cosine similarity and the gray-level co-occurrence matrix parameters of imaging results. The experiments confirm the effectiveness of the dual-modality imaging parameters for skin tissue structure discrimination and assessment. It shows the potential of the proposed method for dermatological practices and lays the foundation for further, in-depth evaluation of the health status of human skin