Nate J. Kemp

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.

Detection of macrophages in atherosclerotic tissue using magnetic nanoparticles and differential phase optical coherence tomography

We demonstrate the detection of iron oxide nanoparticles taken up by macrophages in atherosclerotic plaque with differential phase optical coherence tomography (DP-OCT). Magneto mechanical detection of nanoparticles is demonstrated in hyperlipidemic Watanabe and balloon-injured fat-fed New Zealand white rabbits injected with monocrystalline iron oxide nanoparticles (MIONs) of < 40 nm diam. MIONs taken up by macrophages was excited by an oscillating magnetic flux density and resulting nanometer tissue surface displacement was detected by DP-OCT. Frequency response of tissue surface displacement in response to an externally applied magnetic flux density was twice the stimulus frequency as expected from the equations of motion for the nanoparticle cluster.

Gas-Cell Referenced Swept Source Phase Sensitive Optical Coherence Tomography

Distinct reference and signal interferometers in combination with a gas-cell spectral reference are employed to increase sensitivity and environmental stability of a swept source phase-sensitive optical coherence tomography. A displacement sensitivity (DS) of 65 pm at 280-μm depth and DS degradation with depth of 0.0015 rad/mm is achieved. Differential DS of 234 pm in a 127-μm -thick scattering phantom is six-fold superior to previously reported values. DS degradation with a depth of 0.026 rad/mm is reported for tissue-like scattering phantoms. Measured depth-dependent DS suggests that digitization time jitter noise contributes to degradation of phase sensitivity with depth.

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.

Complex polarization ratio to determine polarization properties of anisotropic tissue using polarization-sensitive optical coherence tomography

Complex polarization ratio (CPR) in materials with birefringence and biattenuance is shown as a logarithmic spiral in the complex plane. A multi-state Levenberg-Marquardt nonlinear fitting algorithm using the CPR trajectory collected by polarization sensitive optical coherence tomography (PS-OCT) was developed to determine polarization properties of an anisotropic scattering medium. The Levenberg-Marquardt nonlinear fitting algorithm using the CPR trajectory is verified using simulated PS-OCT data with speckle noise. Birefringence and biattenuance of a birefringent film, ex-vivo rodent tail tendon and in-vivo primate retinal nerve fiber layer were determined using measured CPR trajectories and the Levenberg-Marquardt nonlinear fitting algorithm.

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.

Safety and efficacy of frequency domain optical coherence tomography in pigs

AIMS To determine the safety and efficacy of frequency domain OCT, which can scan at much higher rates and make it possible to avoid an occlusion balloon and image during an angiographic injection through guide catheter. The catheters have diameters ranging from 2.7 to 3.5 Fr. The presence of the imaging catheter increases fluid resistance to the injection of viscous solutions necessary for clearing the blood. METHODS AND RESULTS The Volcano 3.5 Fr frequency domain OCT catheter system was investigated for safety in (a) n=10 porcine studies using acute and 30-day histology, and (b) for efficacy in n=9 in vivo porcine coronary arteries. We found: (a) frequency domain imaging is safe in the porcine model using histology as an endpoint; (b) the addition of a viscous contrast (iodixonal) to saline is superior for lumen clearance compared to saline alone; (c) hand injection, 4 ml/sec, and 6 ml/sec power injection all provided similar vessel wall clearance; (d) the anticipated loss of vessel wall visualisation with left main injection (due to half the injectate in the non-imaged vessel) was not evident in proximal and middle coronary artery OCT catheter positions. CONCLUSIONS Frequency domain OCT is safe and efficacious in the porcine model.