Marinko V. Sarunic

Sensitivity advantage of swept source and Fourier domain optical coherence tomography

We present theoretical and experimental results which demonstrate the superior sensitivity of swept source (SS) and Fourier domain (FD) optical coherence tomography (OCT) techniques over the conventional time domain (TD) approach. We show that SS- and FD-OCT have equivalent expressions for system signal-to-noise ratio which result in a typical sensitivity advantage of 20-30dB over TD-OCT. Experimental verification is provided using two novel spectral discrimination (SD) OCT systems: a differential fiber-based 800nm FD-OCT system which employs deep-well photodiode arrays, and a differential 1300nm SS-OCT system based on a swept laser with an 87nm tuning range.

Instantaneous complex conjugate resolved spectral domain and swept-source OCT using 3x3 fiber couplers

We report that the complex conjugate artifact in Fourier domain optical coherence tomography approaches (including spectral domain and swept source OCT) may be resolved by the use of novel interferometer designs based on 3x3 and higher order fiber couplers. Interferometers built from NxN (N>2) truly fused fiber couplers provide simultaneous access to non-complementary phase components of the complex interferometric signal. These phase components may be converted to quadrature components by trigonometric manipulation, then inverse Fourier transformed to obtain A-scans and images with resolved complex conjugate artifact. We demonstrate instantaneous complex conjugate resolved Fourier domain OCT using 3x3 couplers in both spectral domain and swept source implementations. Complex conjugate artifact suppression by factors of ~20dB and ~25dB are demonstrated for spectral domain and swept source implementations, respectively.

Frequency estimation precision in Doppler optical coherence tomography using the Cramer-Rao lower bound

Doppler optical coherence tomography (DOCT) is a technique for simultaneous cross-sectional imaging of tissue structure and blood flow. We derive the fundamental uncertainty limits on frequency estimation precision in DOCT using the Cramer-Rao lower bound in the case of additive (e.g., thermal, shot) noise. Experimental results from a mirror and a scattering phantom are used to verify the theoretical limits. Our results demonstrate that the stochastic nature of frequency noise influences the precision of flow imaging, and that the noise model must be selected judiciously in order to estimate the frequency precision.

Imaging the Ocular Anterior Segment With Real-Time, Full-Range Fourier-Domain Optical Coherence Tomography

We have demonstrated a novel Fourier-domain optical coherence tomography system and signal-processing algorithm for full-range, real-time, artifact-free quantitative imaging of the anterior chamber. Cross-sectional full-range images comprising 1024 x 800 pixels (axial x lateral) were acquired and displayed at 6.7 images/s. Volumetric data comprising 1024 x 400 x 60 pixels (axial x lateral x elevation) were acquired in 4.5 seconds with real-time visualization of individual slices and 3-dimensional reconstruction performed in postprocessing. Details of the cornea, limbus, iris, anterior lens capsule, trabecular meshwork, and Schlemms canal were visualized. Quantitative surface height maps of the corneal epithelium and endothelium were obtained from the volumetric data and used to generate corneal thickness maps.

Handheld forward-imaging needle endoscope for ophthalmic optical coherence tomography inspection

We report the narrowest to-date (21 gauge, 820-microm-diam) handheld forward-imaging optical coherence tomography (OCT) needle endoscope and demonstrate its feasibility for ophthalmic OCT inspection. The probe design is based on paired-angle-rotation scanning (PARS), which enables a linear B-scan pattern in front of the probe tip by using two counterrotating angle polished gradient-index (GRIN) lenses. Despite its small size, the probe can provide a numerical apertune (NA) of 0.22 and an experimental sensitivity of 92 dB at 0.5 frames. The feasibility of retinal imaging is tested on enucleated ex vivo porcine eyes, where structural features including remnant vitreous humor, retina, and choroid can be clearly distinguished. Due to its imaging quality comparable to a commercial OCT system and compatibility with the current ophthalmic surgery standard, the probe can potentially serve as a better alternative to traditional visual inspection by white light illumination during vitreoretinal surgery (e.g., vitrectomy).

Segmentation of Intra-Retinal Layers From Optical Coherence Tomography Images Using an Active Contour Approach

Optical coherence tomography (OCT) is a noninvasive, depth-resolved imaging modality that has become a prominent ophthalmic diagnostic technique. We present a semi-automated segmentation algorithm to detect intra-retinal layers in OCT images acquired from rodent models of retinal degeneration. We adapt Chan-Veses energy-minimizing active contours without edges for the OCT images, which suffer from low contrast and are highly corrupted by noise. A multiphase framework with a circular shape prior is adopted in order to model the boundaries of retinal layers and estimate the shape parameters using least squares. We use a contextual scheme to balance the weight of different terms in the energy functional. The results from various synthetic experiments and segmentation results on OCT images of rats are presented, demonstrating the strength of our method to detect the desired retinal layers with sufficient accuracy even in the presence of intensity inhomogeneity resulting from blood vessels. Our algorithm achieved an average Dice similarity coefficient of 0.84 over all segmented retinal layers, and of 0.94 for the combined nerve fiber layer, ganglion cell layer, and inner plexiform layer which are the critical layers for glaucomatous degeneration.

Real-time quadrature projection complex conjugate resolved Fourier domain optical coherence tomography

We present a novel algorithm for full-range imaging by suppression of the complex conjugate artifact in phase-shifting Fourier domain optical coherence tomography. This technique utilizes the projection of multiple phase-shifted interferograms onto an orthogonal basis set to reconstruct the complex interferogram. Full-range imaging with >30 dB suppression of the symmetric artifact is demonstrated using a 3 x 3 fiber coupler swept source OCT system, providing a depth range of 6.6mm with -8 dB roll-off in sensitivity at the depth boundaries relative to DC. Real-time display of full-range images of the anterior segment of the human eye acquired in vivo at a line rate of 6.67 kHz are presented.

Detailed visualization of the anterior segment using fourier-domain optical coherence tomography.

OBJECTIVE To study details of the anterior chamber drainage angle using Fourier-domain optical coherence tomography in healthy subjects and patients with angle abnormalities. METHODS A high-speed anterior segment optical coherence tomography prototype was developed using a 1310-nm-wavelength swept light source. Six healthy subjects and 6 patients with glaucoma were imaged in an observational cross-sectional study. RESULTS Schlemms canal and the trabecular meshwork were visualized in all of the patients. Fifteen-millimeter scans enabled entire anterior segment visualization providing configuration details of the iris with respect to the angle. Four-millimeter scans permitted detailed views of the angle configuration and its structures. Volumetric imaging was possible and Schlemms canal was visualized along part of its circumference. CONCLUSION Anterior segment Fourier-domain optical coherence tomography permits detailed noncontact imaging of the angle and its structures, providing a tool to improve our understanding of the pathogenesis of narrow-angle glaucoma.

Graphics processing unit accelerated optical coherence tomography processing at megahertz axial scan rate and high resolution video rate volumetric rendering

Abstract. In this report, we describe how to highly optimize a computer unified device architecture based platform to perform real-time processing of optical coherence tomography interferometric data and three-dimensional (3-D) volumetric rendering using a commercially available, cost-effective, graphics processing unit (GPU). The maximum complete attainable axial scan processing rate, including memory transfer and displaying B-scan frame, was 2.24 MHz for 16 bits pixel depth and 2048 fast Fourier transform size; the maximum 3-D volumetric rendering rate, including B-scan, en face view display, and 3-D rendering, was ∼23  volumes/second (volume size: 1024×256×200). To the best of our knowledge, this is the fastest processing rate reported to date with a single-chip GPU and the first implementation of real-time video-rate volumetric optical coherence tomography (OCT) processing and rendering that is capable of matching the acquisition rates of ultrahigh-speed OCT.

Chronic and acute models of retinal neurodegeneration TrkA activity are neuroprotective whereas p75NTR activity is neurotoxic through a paracrine mechanism.

In normal adult retinas, NGF receptor TrkA is expressed in retinal ganglion cells (RGC), whereas glia express p75NTR. During retinal injury, endogenous NGF, TrkA, and p75NTR are up-regulated. Paradoxically, neither endogenous NGF nor exogenous administration of wild type NGF can protect degenerating RGCs, even when administered at high frequency. Here we elucidate the relative contribution of NGF and each of its receptors to RGC degeneration in vivo. During retinal degeneration due to glaucoma or optic nerve transection, treatment with a mutant NGF that only activates TrkA, or with a biological response modifier that prevents endogenous NGF and pro-NGF from binding to p75NTR affords significant neuroprotection. Treatment of normal eyes with an NGF mutant-selective p75NTR agonist causes progressive RGC death, and in injured eyes it accelerates RGC death. The mechanism of p75NTR action during retinal degeneration due to glaucoma is paracrine, by increasing production of neurotoxic proteins TNF-α and α2-macroglobulin. Antagonists of p75NTR inhibit TNF-α and α2-macroglobulin up-regulation during disease, and afford neuroprotection. These data reveal a balance of neuroprotective and neurotoxic mechanisms in normal and diseased retinas, and validate each neurotrophin receptor as a pharmacological target for neuroprotection.