Haitham N. Zaatari

High-sensitivity determination of birefringence in turbid media with enhanced polarization-sensitive optical coherence tomography

Polarization-sensitive optical coherence tomography provides high-resolution cross-sectional characterization of birefringence in turbid media. Weakly birefringent biological tissues such as the retinal nerve fiber layer (RNFL) require advanced speckle noise reduction for high-sensitivity measurement of form birefringence. We present a novel method for high-sensitivity birefringence quantification by using enhanced polarization-sensitive optical coherence tomography (EPS-OCT) and introduce the polarimetric signal-to-noise ratio, a mathematical tool for analyzing speckle noise in polarimetry. Multiple incident polarization states and non-linear fitting of normalized Stokes vectors allow determination of retardation with +/-1 degrees uncertainty with invariance to unknown unitary polarization transformations. Results from a weakly birefringent turbid film and in vivo primate RNFL are presented. In addition, we discuss the potential of EPS-OCT for noninvasive quantification of intracellular filamentous nanostructures, such as neurotubules in the RNFL that are lost during the progression of glaucoma.

Detection of vulnerable plaque in a murine model of atherosclerosis with optical coherence tomography

The aim of this study was to evaluate the feasibility of optical coherence tomography (OCT) to identify the components of vulnerable plaques in a well‐established murine model of human atherosclerosis.

Form-biattenuance in fibrous tissues measured with polarization-sensitive optical coherence tomography (PS-OCT)

Form-biattenuance ( chi) in biological tissue arises from anisotropic light scattering by regularly oriented cylindrical fibers and results in a differential attenuation (diattenuation) of light amplitudes polarized parallel and perpendicular to the fiber axis (eigenpolarizations). Form-biattenuance is complimentary to form-birefringence (n) which results in a differential delay (phase retardation) between eigenpolarizations. We justify the terminology and motivate the theoretical basis for form-biattenuance in depth-resolved polarimetry. A technique to noninvasively and accurately quantify form-biattenuance which employs a polarization-sensitive optical coherence tomography (PS-OCT) instrument in combination with an enhanced sensitivity algorithm is demonstrated on ex vivo rat tail tendon (mean chi = 5.3.10-4, N = 111), rat Achilles tendon ( chi = 1.3.10-4, N = 45), chicken drumstick tendon ( chi = 2.1.10-4, N = 57), and in vivo primate retinal nerve fiber layer ( chi = 0.18.10-4, N = 6). A physical model is formulated to calculate the contributions of chi and n to polarimetric transformations in anisotropic media.

Depth-resolved optic axis orientation in multiple layered anisotropic tissues measured with enhanced polarization-sensitive optical coherence tomography (EPS-OCT)

Enhanced polarization-sensitive optical coherence tomography (EPS-OCT) is a noninvasive cross-sectional imaging technique capable of quantifying with high sensitivity the optically anisotropic properties of fibrous tissues. We present a method to measure the depth-resolved optic axis orientations in superficial and deep regions of multiple-layered form-birefringent tissue. Additionally, the bulk-optic EPS-OCT instrument provides anatomical fiber direction referenced absolutely to the laboratory frame, in contrast with fiber-based PS-OCT instruments which provide relative optic axis orientation measurements. Results presented on ex vivo murine tail tendon and porcine annulus fibrosis indicate that the method iscapable of characterizing depth-resolved fiber direction [ theta(z)], form-birefringence [Deltan(z)], and form-biattenuance [Delta chi(z)] for at least 10 successive lamellae and a depth of 0.52 mm into the intervertebral disc. Noninvasive assessment of optic axis orientation by EPS-OCT provides increased contrast in images of multiple-layered media and may improve the understanding of fibrous tissue ultrastructure and the diseases or traumas that affect fibrous tissues.

Differential geometry of normalized Stokes vector trajectories in anisotropic media

Trajectory of the normalized Stokes vector on the Poincaré sphere corresponding to light propagation in anisotropic tissues with birefringence and biattenuance is derived. Analytic expressions are determined from the Serret-Frenet formulas and derivatives of arc length for five quantities including the tangent, normal, and binormal vectors with curvature and torsion. Depth variation of curvature and torsion of normalized Stokes vector trajectories corresponding to light propagating in rodent tail tendon are given. Use of analytic expressions for depth variation of curvature and torsion of the normalized Stokes vector trajectories on the Poincaré sphere is discussed for analysis of polarization-sensitive optical coherence tomography data recorded from anisotropic biological tissues with birefringence and biattenuance.

Fibre orientation contrast for depth-resolved identification of structural interfaces in birefringent tissue

Incorporation of polarimetric sensitivity into optical coherence tomography can provide additional image contrast when structures of interest are optically anisotropic (e.g., fibrous tissue). We present a generalized technique based on polarization-sensitive optical coherence tomography to detect changes in depth-resolved fibre orientation and thus increase image contrast in multiple-layered birefringent tissues. A high contrast B-scan image of collagen fibre orientation is shown for a porcine intervertebral disc cartilage specimen that exhibited low backscattering intensity contrast. Interfaces in the annulus fibrosus identified using depth-resolved fibre orientation allowed quantification of lamellae thickness. Moreover, the technique detects changes in fibre orientation without intense processing needed to effectively quantify tissue retardation and diattenuation.

Characterizing Cartilage Ultrastructure Using Noninvasive Depth-Resolved Polarimetric Imaging

Using enhanced polarization-sensitive optical coherence tomography (EPS-OCT), we demonstrate visualization and quantification of collagen fiber ultrastructure in cartilage. This is important for understanding the physiological and mechanical properties of cartilage and its associated diseases.

Retardation measurement with capillary blood flow using enhanced polarization-sensitivity optical coherence tomography (EPS-OCT)

Polarization-Sensitive Optical Coherence Tomography (PS-OCT) has been used to measure birefringence of biological samples, namely the retinal nerve fiber layer (RNFL). The presence of blood vessels in biological samples complicates accurate measurement of tissue birefringence as a result of the Doppler shift in fringe frequency and the shadowing effect below blood vessels due to absorption and scattering of light photons by blood. We investigate phase retardation measurement with controlled capillary blood flow overlying a birefringent sample with enhanced polarization-sensitivity optical coherence tomography (EPS-OCT). The effect of blood flow on the calculation of phase retardation and tissue birefringence was studied in the polarization domain. Light propagating through an overlying moving turbid medium (blood) undergoes single or multiple forward scattering events and a Doppler shift in presence of flow. Light propagating through an overlying medium may introduce Doppler shifts of each polarization component and/or polarization shifts or retardation of light. While undergoing multiple forward scattering, each scattering event can modify the frequency or light phase delay. In successive scattering events, potential Doppler shifts and/or polarization shifts accumulate. Light propagating within the birefringent sample undergoes multiple forward scattering events leading to phase retardation between polarization components. This paper investigates phase retardation measurement underlying physiological blood flow rates (6, 12, 18, and 24μl/min) at a range of light incident angle (0-20 deg.) on the sample. With EPS-OCT, the effect of light scattering and differential Doppler shifts between the polarization modes on the measurement of phase retardation was within our speckle noise range.

Birefringence and nerve fiber orientation in healthy in vivo primate RNFL with enhanced polarization-sensitive optical coherence tomography (EPS-OCT)

Form-birefringent properties of the retinal nerve fiber layer (RNFL) have become increasingly important as investigators strive to provide an improved methodology for glaucoma diagnosis. Techniques such as scanning laser polarimetry (SLP) and polarization-sensitive optical coherence tomography (PS-OCT) are two approaches which directly assess RNFL neurotubules, the sub-cellular structures responsible for form-birefringence and axoplasmic transport in retinal ganglion cell axons. We present a novel algorithm for enhancing the sensitivity of PS-OCT. Enhanced polarization-sensitive OCT (EPS-OCT) is capable of detecting small transformations in polarization typically experienced by light propagating through the thin and weakly birefringent primate RNFL. We report birefringence and nerve fiber orientation measurements for the peripapillary region in healthy in vivo primate RNFL and discuss the implications of the enhanced-sensitivity approach on noninvasive quantification of form-birefringence in glaucoma diagnostics.ABSTRACT Form-birefringent properties of the retinal nerve fiber layer (RNFL) have become increasingly important asinvestigators strive to provide an improved methodology for glaucoma diagnosis. Techniques such as scanning laserpolarimetry (SLP) and polarization-sensitive optical coherence tomography (PS-OCT) are two approaches whichdirectly assess RNFL neurotubules, the sub-cellular structures responsible for form-birefringence and axoplasmictransport in retinal ganglion cell axons. We present a novel algorithm for enhancing the sensitivity of PS-OCT.Enhanced polarization-sensitive OCT (EPS-OCT) is capable of detecting small transformations in polarization typicallyexperienced by light propagating through the thin and weakly birefringent primate RNFL. We report birefringence andnerve fiber orientation measurements for the peripapillary region in healthy in vivo primate RNFL and discuss theimplications of the enhanced-sensitivity approach on noninvasive quantification of form-birefringence in glaucomadiagnostics.Keywords: Glaucoma, retinal nerve fiber layer, birefringence, retardation, axis orientation, polarization, opticalcoherence tomography, neurotubules

Polarization-sensitive optical coherence tomography with de-correlated channels

We describe a Polarization Sensitive Optical Coherence Tomography (PS-OCT) system with de-correlated horizontal and vertical channels. Construction of PS-OCT depth-resolved images is achieved with a scanning bulk Michelson interferometer and a broadband TiAl2O3 femtosecond laser source. We de-correlate and delay horizontal and vertical channels using a birefringent crystal in the source path and calcite prism pairs in the sample and reference paths. Cross-correlation and phase changes between horizontal and vertical channels are measured at different reference-sample optical delays in correlated and de-correlated PS-OCT. PS-OCT with de-correlated (DPS-OCT) channels can broaden applications to include de-correlated Doppler imaging of blood flow and imaging the retinal nerve fiber layer with delayed channels. We achieve a differential delay of 0-400 microns between vertical and horizontal channels by translating the calcite prisms. DPS-OCT system design and experimental measurements are presented and discussed.