SNR enhancement through phase dependent signal reconstruction algorithms for phase separated interferometric signals

We report several signal reconstruction algorithms for processing phase separated homodyne interferometric signals. Methods that take advantage of the phase of the signal are experimentally shown to achieve a signal-to-noise ratio (SNR) improvement of up to 5 dB over commonly used algorithms. To begin, we present a derivation of the SNR resulting from five image reconstruction algorithms in the context of a 3x3 fiber-coupler based homodyne optical coherence tomography (OCT) system, and clearly show the improvement in SNR associated with phase-based algorithms. Finally, we experimentally verify this improvement and demonstrate the enhancement in contrast and improved image quality afforded by these algorithms through homodyne OCT imaging of a Xenopus laevis tadpole. These algorithms can be generally applied in signal extraction processing where multiple phase separated measurements are available

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

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

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

We report the narrowest to-date (21 gauge, 820-µm-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)

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

Subconjunctival delivery of p75NTR antagonists reduces the inflammatory, vascular, and neurodegenerative pathologies of diabetic retinopathy

The p75NTR is a novel therapeutic target validated in a streptozotocin mouse model of diabetic retinopathy. Intravitreal (IVT) injection of small molecule p75NTR antagonist THX-B was therapeutic and resolved the inflammatory, vascular, and neurodegenerative phases of the retinal pathology. To simplify clinical translation, we sought a superior drug delivery method that circumvents risks associated with IVT injections. METHODS. We compared the pharmacokinetics of a single 40 lg subconjunctival (SCJ) depot to the reported effective 5 lg IVT injections of THX-B. We quantified therapeutic efficacy, with endpoints of inflammation, edema, and neuronal death. RESULTS. The subconjunctival depot affords retinal exposure equal to IVT injection, without resulting in detectable drug in circulation. At week 2 of diabetic retinopathy, the SCJ depot provided therapeutic efficacy similar to IVT injections, with reduced inflammation, reduced edema, reduced neuronal death, and a long-lasting protection of the retinal structure. CONCLUSIONS. Subconjunctival injections are a safe and effective route for retinal delivery of p75NTR antagonists. The subconjunctival route offers an advantageous, less-invasive, more compliant, and nonsystemic method to deliver p75NTR antagonists for the treatment of retinal diseases.Fil: Galan, Alba. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Barcelona, Pablo Federico. Mc Gill University. Lady Davis Research Intitute; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Nedev, Hinyu. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Sarunic, Marinko V.. University Fraser Simon; CanadáFil: Jian, Yifan. University Fraser Simon; CanadáFil: Saragovi, H. Uri. Mc Gill University. Lady Davis Research Intitute; Canad

Molecular contrast optical coherence tomography: SNR comparison of techniques and introduction of ground state recovery pump-probe OCT

Molecular contrast OCT (MCOCT) is an extension of OCT in which specific molecular species are imaged based on their spectroscopic characteristics. In order to improve the sensitivity and specificity of MCOCT, several techniques have recently been introduced which depend upon coherent detection of inelastically scattered light from molecules of interest in a sample. These techniques include harmonic generation, coherent anti-Stokes Raman scattering, and several different forms of pump-probe spectroscopy. We have developed a theoretical framework to facilitate the comparison of different inelastic scattering-based contrast mechanisms for molecular contrast OCT. This framework is based upon the observation that since the noise floor is defined by the reference arm power in a shot-noise limited heterodyne detection system, the relevant comparison among the techniques is isolated to the available molecular-specific signal power. We have derived the value of the molecular contrast signal power for second harmonic generation OCT (SHOCT) and three different pump-probe OCT (PPOCT) techniques. Motivated by this analysis, we have constructed a preliminary ground state recovery pump-probe OCT system, and demonstrated its performance using rhodamine 6G as the MCOCT contrast agent

Instantaneous complex spectral domain OCT using 3x3 fiber couplers

We report that the complex conjugate ambiguity in spectral domain OCT approaches (including swept source OCT and Fourier-domain OCT) may be removed by the use of novel interferometer designs based on NxN couplers. An interferometer based on a 3x3 truly fused fiber coupler with equal splitting ratios provides simultaneous access to components of the complex interferometric signal separated by 120o. These phase components may be converted to quadrature components by use of a simple trigonometric operation, and then inverse Fourier transformed to obtain A-scans and images free of complex conjugate artifact. We demonstrate instantaneous complex spectral-domain OCT using a novel Fourier-domain OCT system employing photodiode arrays, and will also report on a similar system design for instantaneous complex swept-source OCT

Endoscopic optical coherence tomography of the retina at 1310 nm using paired-angle rotating scanning

Vitrectomy (removal of the vitreous humor) is an ophthalmic surgery required as a precursor to several posterior chamber procedures. Vitrectomy is commonly performed using an endoscopic vitreous cutter and fiber based light delivery for observation through a surgical microscope. Cross-sectional visualization of the retina and remnant vitreous layers during surgery using an external optical coherence tomography (OCT) scanner is impractical due to deformation in the shape of the eye and the cornea. We present a forward imaging probe with 820 &mgr;m outer diameter (21 gauge needle) for cross-sectional endoscopic OCT imaging during ophthalmic surgeries. The Paired-Angle-Rotating Scanner (PARS) OCT probe is based on angle polished gradient index (GRIN) lenses which are rotated about the optical axis. The scan pattern is determined by the angle between the GRIN lenses and the relative angular velocity. Endoscopic placement of the PARS-OCT probe tip near the retinal surface permits use of a longer wavelength light, in particular 1310 nm, which would otherwise suffer significant attenuation traversing the vitreous humor. The prototype endoscopic PARS-OCT probe is coupled to a commercially available 1310 nm swept laser source, and uses commercial software for data acquisition, processing, and display of retinal images in real time at an A-scan rate of 16 kHz. We present an analysis of aberrations due to off axis use of GRIN lenses and measure the scan pattern of the PARS probe. Images acquired on an ex vivo porcine retina are presented, motivating development of the endoscopic PARS-OCT probe for clinical evaluation