Towards Improved Collagen Assessment: Polarization-Sensitive Optical Coherence Tomography with Tailored Reference Arm Polarization

Single channel PS-OCT has advantages for assessing birefringent tissue components in various clinical scenarios, with implications for assessing pathology, ranging from osteoarthritis to myocardial infarction. While the technique has been successfully used both in vitro and in vivo, there have been limited attempts to optimize single channel PS-OCT with respect to performance, particularly paddle rotation. In this study, we developed and tested a new approach for the real-time assessment of birefringence through tailoring of reference arm polarization. Different polarization rotation patterns, as depicted on a Poincare sphere, were assessed with polarization filters and retarders. When further tested in tissue, PS-OCT assessments of bovine cartilage and tendon demonstrated that contrast was sensitive to the pattern selected, indicating that rotation pattern influenced birefringence assessment and providing insights into optimal patterns. We also discuss the difference between diagnostic accuracy and precision with respect to both the construction and application of PS-OCT embodiments

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

Extracting structural features of rat sciatic nerve using polarization-sensitive spectral domain optical coherence tomography

We present spectral domain polarization-sensitive optical coherence tomography (SD PS-OCT) imaging of peripheral nerves. Structural and polarization-sensitive OCT imaging of uninjured rat sciatic nerves was evaluated both qualitatively and quantitatively. OCT and its functional extension, PS-OCT, were used to image sciatic nerve structure with clear delineation of the nerve boundaries to muscle and adipose tissues. A long-known optical effect, bands of Fontana, was also observed. Postprocessing analysis of these images provided significant quantitative information, such as epineurium thickness, estimates of extinction coefficient and birefringence of nerve and muscle tissue, frequency of bands of Fontana at different stretch levels of nerve, and change in average birefringence of nerve under stretched condition. We demonstrate that PS-OCT combined with regular-intensity OCT (compared with OCT alone) allows for a clearer determination of the inner and outer boundaries of the epineurium and distinction of nerve and muscle based on their birefringence pattern. PS-OCT measurements on normal nerves show that the technique is promising for studies on peripheral nerve injury. © 2012 Society of Photo-Optical Instrumentation Engineers (SPIE)

Multimodal Optical Medical Imaging Concepts Based on Optical Coherence Tomography

Optical medical imaging techniques in general exhibit outstanding resolution and molecule-specific contrast. They come however with a limited penetration in depth and small field of view. Multimodal concepts help to combine complementary strengths of different imaging technologies. The present article reviews the advantages of optical multimodal imaging concepts using optical coherence tomography (OCT) as core technology. In particular we first discuss polarization sensitive OCT, Doppler OCT and OCT angiography, OCT elastography, and spectroscopic OCT as intramodal concepts. To highlight intermodal imaging concepts, we then chose the combination of OCT with photoacoustics, and with non-linear optical microscopy. The selected multimodal concepts and their particular complementary strengths and applications are discussed in detail. The article concludes with notes on standardization of OCT imaging and multimodal extensions

Rapid wide-field imaging of soft-tissue microstructure

Tissue microstructure is pivotal in determining the function, behavior, and disease state of biological tissues. Histology and advanced optical techniques are commonly used to examine the cellular, extracellular, and subcellular constituents that define tissue microstructure. However, these techniques frequently require tedious and destructive tissue preparations and lengthy imaging times, or have limited fields of view. Therefore, it is challenging to study soft-tissue microstructure within the macroscopic spatial and temporal context of tissue- and organ-level function. Wide-field imaging techniques provide a non-destructive alternative to rapidly assess tissue microstructure across macroscopic fields of view. Rather than resolving microstructure directly, these techniques are sensitive to light-scattering characteristics of tissue that indicate the underlying microstructure. This dissertation develops light-scattering models to interpret tissue microstructure from light-scattering across macroscopic fields of view rapidly and non-destructively. The first half of the dissertation uses spatial frequency domain imaging (SFDI) to quantify the sub-diffuse light-scattering characteristics of tissues that are intrinsically linked to microstructure. It then introduces a novel empirical model which allows rapid fitting of SFDI data and is sensitive to changes in microparticle size. This technique is then demonstrated as a potential surgical guidance tool for Mohs Micrographic Surgery by rapidly and non-destructively demarcating tumor boundaries in skin biopsies. The imaging and processing speeds achieved with this technique can improve clinical workflows, particularly tissue-conserving surgical procedures, which are currently hindered by the time necessary to determine tumor boundaries using histopathology. Improvements to this technique by use of higher spatial frequencies are also considered. The second section investigates polarization-dependent scattering in tissues that is a result of collagen fiber microstructure. An experimentally-validated computational model is developed to allow direct conversion of polarized-light measurements into absolute measures of collagen fiber alignment in tissues. Furthermore, a combined polarized light SFDI system (pSFDI) is demonstrated to measure distinct fiber alignments in multi-layered tissue samples. The increased speed and versatility of this system is employed to map wide-field microfiber kinematics during mechanical tissue deformation. This technique enables direct examination of the contributions of local fiber kinematics to tissue- and organ-level scales of growth and remodeling.Biomedical Engineerin

Multi-contrast Jones-matrix optical coherence tomography -- the concept, principle, implementation, and applications

Jones-matrix optical coherence tomography (JM-OCT) is an extension of OCT that provides multiple types of optical contrasts of biological and clinical samples. JM-OCT measures the spatial distribution of the Jones matrix of the sample and also its time sequence. All contrasts (i.e., multi-contrast OCT images) are then computed from the Jones matrix. The contrasts obtained from the Jones matrix include the conventional and polarization-insensitive OCT intensity, cumulative and local phase retardation (birefringence), degree-of-polarization uniformity quantifying the polarization randomness of the sample, signal attenuation coefficient, sample scatterer density, Doppler OCT, OCT angiography, and dynamic OCT. JM-OCT is a generalized version of OCT because it measures the generalized form of the sample information; i.e., the Jones matrix sequence. This review summarizes the basic conception, mathematical principle, hardware implementation, signal and image processing, and biological and clinical applications of JM-OCT. Advanced technical topics, including JM-OCT-specific noise correction and quantity estimation and JM-OCT's self-calibration nature, are also described

Deep tissue volume imaging of birefringence through fibre-optic needle probes for the delineation of breast tumour

Published online: 01 July 2016Identifying tumour margins during breast-conserving surgeries is a persistent challenge. We have previously developed miniature needle probes that could enable intraoperative volume imaging with optical coherence tomography. In many situations, however, scattering contrast alone is insufficient to clearly identify and delineate malignant regions. Additional polarization-sensitive measurements provide the means to assess birefringence, which is elevated in oriented collagen fibres and may offer an intrinsic biomarker to differentiate tumour from benign tissue. Here, we performed polarization-sensitive optical coherence tomography through miniature imaging needles and developed an algorithm to efficiently reconstruct images of the depth-resolved tissue birefringence free of artefacts. First ex vivo imaging of breast tumour samples revealed excellent contrast between lowly birefringent malignant regions, and stromal tissue, which is rich in oriented collagen and exhibits higher birefringence, as confirmed with co-located histology. The ability to clearly differentiate between tumour and uninvolved stroma based on intrinsic contrast could prove decisive for the intraoperative assessment of tumour margins.Martin Villiger, Dirk Lorenser, Robert A. McLaughlin, Bryden C. Quirk, Rodney W. Kirk, Brett E. Bouma and David D. Sampso

Polarization-sensitive optical frequency domain imaging based on unpolarized light

Polarization-sensitive optical coherence tomography (PS-OCT) is an augmented form of OCT, providing 3D images of both tissue structure and polarization properties. We developed a new method of polarization-sensitive optical frequency domain imaging (PS-OFDI), which is based on a wavelength-swept source. In this method the sample was illuminated with unpolarized light, which was composed of two orthogonal polarization states (i.e., separated by 180° in the Poincaré sphere) that are uncorrelated to each other. Reflection of these polarization states from within the sample was detected simultaneously and independently using a frequency multiplexing scheme. This simultaneous sample probing with two polarization states enabled determination of the depth-resolved Jones matrices of the sample. Polarization properties of the sample were obtained by analyzing the sample Jones matrices through eigenvector decomposition. The new PS-OFDI system ran at 31K wavelength-scans/s with 3072 pixels per wavelength-scan, and was tested by imaging a polarizer and several birefringent tissues such as chicken muscle and human skin. Lastly the new PS-OFDI was applied to imaging two cancer animal models: a mouse model by injecting cancer cells and a hamster cheek pouch model. These animal model studies demonstrated the significant differences in tissue polarization properties between cancer and normal tissues in vivo. © 2011 Optical Society of America

Polarization-sensitive optical coherence tomography with a conical beam scan for the investigation of birefringence and collagen alignment in the human cervix

By measuring the phase retardance of a cervical extracellular matrix, our in-house polarization-sensitive optical coherence tomography (PS-OCT) was shown to be capable of (1) mapping the distribution of collagen fibers in the non-gravid cervix, (2) accurately determining birefringence, and (3) measuring the distinctive depolarization of the cervical tissue. A conical beam scan strategy was also employed to explore the 3D orientation of the collagen fibers in the cervix by interrogating the samples with an incident light at 45° and successive azimuthal rotations of 0-360°. Our results confirmed previous observations by X-ray diffraction, suggesting that in the non-gravid human cervix collagen fibers adjacent to the endocervical canal and in the outermost areas tend to arrange in a longitudinal fashion whereas in the middle area they are oriented circumferentially. PS-OCT can assess the microstructure of the human cervical collagen in vitro and holds the potential to help us better understand cervical remodeling prior to birth pending the development of an in vivo probe