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Over the past 5 years, visible light Optical Coherence Tomography (OCT) has emerged as a promising technique for ultrahigh resolution microstructural imaging and depth-resolved imaging of chromophores. In the retina, visible light OCT can simultaneously induce and observe retinal changes during the phototransduction cascade, including bleaching-related absorption changes, as well as intrinsic scattering, cell swelling, and possible longer-term changes in retinal chromophores. Here we investigate outer retinal reflectance changes during visible light OCT in mice to better understand the contributions of these various signals. All experiments were performed on pigmented (C57BL/6J) and albino (BALB/c) mice in an initially dark-adapted state. There were no consistent reflectance changes in any layers including and proximal to the External Limiting Membrane (ELM). However, reflectance increased in the inner segment / outer segment (IS / OS) junction and outer segments tips (OST) of both strains. Layers distal to the photoreceptors such as the Retinal Pigment Epithelium (RPE), Bruch’s membrane (BM), and choroid showed a consistent increase in pigmented mice and showed no significant change in albino mice. Though our results are qualitatively well-explained by results from photopigment bleaching and intrinsic optical signal experiments in the literature, the time scale of some of the changes observed in our study is too long, which could indicate either signals with a different physiological origin or the need for a more precise model to describe imaging and stimulation using the same beam profile.

Interferometric near-infrared spectroscopy (iNIRS) is a time-of-flight- (TOF-) resolved sensing method for direct and simultaneous quantification of tissue optical properties (absorption and reduced scattering) and dynamics (blood flow index) in vivo with a single modality. The technique has previously been validated in Intralipid phantoms, and applied to continuously and non-invasively monitor optical properties and blood flow index in the brains of head-fixed, anesthetized mice. A demonstration of robust iNIRS measurements in human tissues with motion would support the viability of iNIRS for clinical applications. Here, we perform non-contact iNIRS in human tissues. We show that phase drift caused by involuntary motion during acquisition significantly distorts the optical field autocorrelation, particularly at early TOFs. To solve this issue, we present a novel numerical phase drift correction method to isolate field dynamics due to just red blood cell motion within the sample. Upon correction, TOF-resolved autocorrelations exhibit exponential decay behavior, whether acquired from Intralipid, the human forearm, or the human forehead. We confirm the link between bulk motion artifacts and phase drift by simultaneous, co-registered iNIRS and Optical Coherence Tomography measurements. By applying conventional, time-resolved diffusion theory and diffusing wave spectroscopy theory, we quantify optical properties and time-of-flight-resolved dynamics in Intralipid, the human forearm, and the human brain. Finally, we explore strategies for increased photon collection through parallelization of iNIRS, to probe greater depths in the human brain. This work conclusively shows that diffuse optical measurements of field dynamics are possible, even in the presence of motion artifacts.

The penetration depth of optical microscopy in biological tissue is limited by attenuation due to absorption and scattering. Scattering decreases with wavelength, while water absorption is locally minimized at so-called infrared “optical windows.” Of the four infrared optical windows, light in the longest wavelength window at 2200 nm experiences the least scattering and the most water absorption. Therefore, the 2200 nm window is rarely used for biological microscopy. However, fractional water content differs greatly between tissues. Therefore, the best optical window for deep imaging may depend on tissue type. Here, we demonstrate the benefits of the 2200 nm optical window for imaging through the skull, which is highly turbid with a relatively low water content. A spectral domain optical coherence tomography (OCT) system at ~2200 nm was built. A maximum sensitivity of 86 dB and a tissue axial resolution of 13.9 µm were achieved. To assess relative contributions of scattering and water absorption, 2200 nm was compared with 1300 nm. In vivo cortical vasculature was imaged angiographically through the intact skull in mice. Overall 2200 nm experienced less attenuation through the intact skull. In cortical layer I, 1300 nm, which experiences more scattering but less water absorption, and 2200 nm, which experiences less scattering but more water absorption, exhibit similar attenuation. In deeper cortical layer II/III, higher attenuation was observed at 2200 nm due to higher water absorption. Thus the infrared window at 2200 nm may provide advantages for imaging layers at or near the cortical surface through thick skull.

© 2016 Elsevier Inc. Purpose To evaluate the diagnostic performance of a 3-dimensional (3D) neuroretinal rim parameter, the minimum distance band (MDB), using optical coherence tomography (OCT) high-density volume scans for open-angle glaucoma. Design Reliability analysis. Methods SETTING: Institutional. STUDY POPULATION: Total of 163 patients (105 glaucoma and 58 healthy subjects). OBSERVATION PROCEDURES: One eye of each patient was included. MDB and retinal nerve fiber layer (RNFL) thickness values were determined for 4 quadrants and 4 sectors using a spectral-domain OCT device. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC) values, sensitivities, specificities, and positive and negative predictive values. Results The best AUROC values of 3D MDB thickness for glaucoma and early glaucoma were for the overall globe (0.969, 0.952), followed by the inferior quadrant (0.966, 0.949) and inferior-temporal sector (0.966, 0.944), and then followed by the superior-temporal sector (0.964, 0.932) and superior quadrant (0.962, 0.924). All 3D MDB thickness AUROC values were higher than those of 2D RNFL thickness. Pairwise comparisons showed that the diagnostic performance of the 3D MDB parameter was significantly better than 2D RNFL thickness only for the nasal quadrant and inferior-nasal and superior-nasal sectors (P = .023–.049). Combining 3D MDB with 2D RNFL parameters provided significantly better diagnostic performance (AUROC 0.984) than most single MDB parameters and all single RNFL parameters. Conclusions Compared with the 2D RNFL thickness parameter, the 3D MDB neuroretinal rim thickness parameter had uniformly equal or better diagnostic performance for glaucoma in all regions and was significantly better in the nasal region.

Visible light optical coherence tomography (OCT) has recently emerged in retinal imaging, with claims of micrometer-scale axial resolution and multi-color (sub-band) imaging. Here, we show that the large dispersion of optical glass and aqueous media, together with broad optical bandwidths often used in visible light OCT, compromises both of these claims. To rectify this, we introduce the notion of spatially dependent (i.e., depth and transverse position-dependent) dispersion. We use a novel sub-band, sub-image correlation algorithm to estimate spatially dependent dispersion in our 109nm bandwidth visible light OCT mouse retinal imaging system centered at 587nm. After carefully compensating spatially dependent dispersion, we achieve delineation of fine outer retinal bands in mouse strains of varying pigmentation. Spatially dependent dispersion correction is critical for broader bandwidths and shorter visible wavelengths.

Quantifying light transport in turbid media is a long-standing challenge. This challenge arises from the difficulty in experimentally separating unscattered, ballistic light from forward scattered light. Correlation gating is a new approach that numerically separates light paths based on statistical dynamics of the optical field. Here we apply correlation gating with interferometric near-infrared spectroscopy (iNIRS) to separate and independently quantify ballistic and scattered light transmitted through thick samples. First, we present evidence that correlation gating improves the isolation of ballistic light in a thick, intrinsically dynamic medium with Brownian motion. Then, from a single set of iNIRS transmission measurements, we determine the ballistic attenuation coefficient and group refractive index from the time-of-flight (TOF) resolved static intensity, and we determine the reduced scattering and absorption coefficients from the diffusive part of the TOF resolved dynamic intensity. Finally, we show that correlation gating is applicable in intrinsically static media in which motion is induced externally. Thus, for the first time, to the best of our knowledge, the key optical properties of a turbid medium can be derived from a single set of transmission measurements.

Optical Coherence Tomography Angiography (OCTA) has recently emerged for imaging vasculature in clinical ophthalmology. Yet, apparent OCTA image artifacts remain challenging to interpret. Here, contrast-enhanced OCTA is employed in rats to help explain these apparent artifacts. By quantifying enhancement due to an intravascular contrast agent with rheological and scattering properties that are different from red blood cells (RBCs), OCTA image features are ascribed to specific rheological and scattering properties of RBCs. By imaging pigmented and unpigmented rats at a wavelength where scattering dominates image contrast (1300 nm), the impact of melanosome scattering on OCT and OCTA signals is determined.

Most flying-spot Optical Coherence Tomography (OCT) and Optical Coherence Microscopy (OCM) systems use a symmetric confocal geometry, where the detection path retraces the illumination path starting from and ending with the spatial mode of a single mode optical fiber. Here, we describe a visible light OCM instrument that breaks this symmetry to improve transverse resolution without sacrificing collection efficiency in scattering tissue. This was achieved by overfilling a 0.3 numerical aperture (NA) water immersion objective on the illumination path, while maintaining a conventional Gaussian mode detection path (1/e2 intensity diameter ~0.82 Airy disks), enabling ~1.1 μm full-width at half-maximum (FWHM) transverse resolution. At the same time, a ~0.9 μm FWHM axial resolution in tissue, achieved by a broadband visible light source, enabled femtoliter volume resolution. We characterized this instrument according to paraxial coherent microscopy theory, and then used it to image the meningeal layers, intravascular red blood cell-free layer, and myelinated axons in the mouse neocortex in vivo through the thinned skull. Finally, by introducing a 0.8 NA water immersion objective, we improved the lateral resolution to 0.44 μm FWHM, which provided a volumetric resolution of ~0.2 fL, revealing cell bodies in cortical layer I of the mouse brain with OCM for the first time.

Chromatic aberrations are an important design consideration in high resolution, high bandwidth, refractive imaging systems that use visible light. Here, we present a fiber-based spectral/Fourier domain, visible light OCT ophthalmoscope corrected for the average longitudinal chromatic aberration (LCA) of the human eye. Analysis of complex speckles from in vivo retinal images showed that achromatization resulted in a speckle autocorrelation function that was ~20% narrower in the axial direction, but unchanged in the transverse direction. In images from the improved, achromatized system, the separation between Bruch’s membrane (BM), the retinal pigment epithelium (RPE), and the outer segment tips clearly emerged across the entire 6.5 mm field-of-view, enabling segmentation and morphometry of BM and the RPE in a human subject. Finally, cross-sectional images depicted distinct inner retinal layers with high resolution. Thus, with chromatic aberration compensation, visible light OCT can achieve volume resolutions and retinal image quality that matches or exceeds ultrahigh resolution near-infrared OCT systems with no monochromatic aberration compensation.

Interferometric near-infrared spectroscopy (iNIRS) is a recently introduced time-of-flight- (TOF-) resolved sensing method for quantifying optical and dynamical properties of turbid media non-invasively. iNIRS measures the interference spectrum of light traversing a turbid medium using a rapidly tunable, or frequency swept, light source. While the modality was successfully demonstrated in vivo in the nude mouse brain for monitoring absorption, reduced scattering, and blood flow index, translation towards human measurements requires improving light collection efficiency. Particularly, interrogating cortical tissue beneath the adult human scalp and skull remains challenging due to the limited core size and throughput of the single mode fiber currently used for detection. To tackle this problem, we implement a short to null source-detector separation geometry setup to significantly improve the number of detected diffuse photons. We discuss both hardware and post-processing improvements to isolate the desired diffuse signal from the large, non-diffuse and specular signals. Furthermore, key improvements in the iNIRS optical system, including higher TOF resolution (22-60 ps), optimized dynamic range (36-47 dB), faster sweep rate (50-500 kHz), and a technique for combining the forward and backward sweeps to double the effective optical field autocorrelation sampling rate, are presented. These allow for more precise and quantitative extraction of in vivo optical properties and TOF-resolved dynamics at long path lengths. Collectively, these key advances in the technology pave the way for translating iNIRS towards non-invasive, real-time, and quantitative measurements of oxygen metabolism and blood perfusion in deep human tissues.

Optical coherence tomography angiography (OCTA) has recently emerged for imaging vasculature in clinical ophthalmology. Yet, OCTA images contain artifacts that remain challenging to interpret. To help explain these artifacts, we perform contrast-enhanced OCTA with a custom-designed wide-field ophthalmoscope in rats in vivo. We choose an intravascular contrast agent (Intralipid) with particles that are more isotropically scattering and more symmetrically shaped than red blood cells (RBCs). Then, by examining how OCTA artifacts change after contrast agent injection, we attribute OCTA artifacts to RBC-specific properties. In this work, we investigate retinal and choroidal OCTA in rats with or without melanosomes, both before and after contrast agent injection, at a wavelength at which scattering dominates the image contrast (1300 nm). First, baseline images suggest that high backscattering of choroidal melanosomes accounts for the relatively dark appearance of choroidal vessel lumens in OCTA. Second, Intralipid injection tends to eliminate the hourglass pattern artifact in OCTA images of vessel lumens and highlights vertical capillaries that were previously faint in OCTA, showing that RBC orientation is important in determining OCTA signal. Third, Intralipid injection increases lumen signal without significantly affecting the tails, suggesting that projection artifacts, or tails, are due to RBC multiple scattering. Fourth, Intralipid injection increases the side-to-top signal ratio less in choroidal vessel lumens of pigmented rats, suggesting that melanosome multiple scattering makes the hourglass artifact less prominent. This study provides the first direct experimental in vivo evidence to explain light scattering-related artifacts in OCTA.

We introduce the feature issue on the Optics in the Life Sciences Congress held on April 2-5, 2017 in San Diego, CA. The Congress consisted of 5 topical symposia: (i) Bio-optics Design and Application; (ii) Novel Techniques in Microscopy; (iii) Optical Molecular Probes, Imaging and Drug Delivery; (iv) Optical Trapping Applications; and (v) Optics and the Brain. These separate symposia also held joint sessions of common interest. The following highlights some of the topics from the Congress.

Most flying-spot optical coherence tomography and optical coherence microscopy (OCM) systems use a symmetric confocal geometry, where the detection path retraces the illumination path starting from and ending with the spatial mode of a single-mode optical fiber. Here we describe a visible light OCM instrument that breaks this symmetry to improve transverse resolution without sacrificing collection efficiency in scattering tissue. This was achieved by overfilling a water immersion objective on the illumination path while maintaining a conventional Gaussian mode detection path (1/e2 intensity diameter ∼0.82 Airy disks), enabling ∼1.1 μm full width at half-maximum (FWHM) transverse resolution. At the same time, a ∼0.9 μm FWHM axial resolution in tissue, achieved by a broadband visible light source, enabled femtoliter volume resolution. We characterized this instrument according to paraxial coherent microscopy theory and, finally, used it to image the meningeal layers, intravascular red blood cell-free layer, and myelinated axons in the mouse neocortex in vivo through the thinned skull.

Light-scattering methods are widely used in soft matter physics and biomedical optics to probe dynamics in turbid media, such as diffusion in colloids or blood flow in biological tissue. These methods typically rely on fluctuations of coherent light intensity, and therefore cannot accommodate more than a few modes per detector. This limitation has hindered efforts to measure deep tissue blood flow with high speed, since weak diffuse light fluxes, together with low single-mode fiber throughput, result in low photon count rates. To solve this, we introduce multimode fiber (MMF) interferometry to the field of diffuse optics. In doing so, we transform a standard complementary metal-oxide-semiconductor (CMOS) camera into a sensitive detector array for weak light fluxes that probe deep in biological tissue. Specifically, we build a novel CMOS-based, multimode interferometric diffusing wave spectroscopy (iDWS) system and show that it can measure ∼20 speckles simultaneously near the shot noise limit, acting essentially as ∼20 independent photon-counting channels. We develop a matrix formalism, based on MMF mode field solutions and detector geometry, to predict both coherence and speckle number in iDWS. After validation in liquid phantoms, we demonstrate iDWS pulsatile blood flow measurements at 2.5 cm source-detector separation in the adult human brain in vivo. By achieving highly sensitive and parallel measurements of coherent light fluctuations with a CMOS camera, this work promises to enhance performance and reduce cost of diffuse optical instruments.

We apply correlation gating with interferometric near-infrared spectroscopy (iNIRS) to separate ballistic and scattered light transmitted through thick samples. By analyzing each component, we determine optical properties of a dynamic medium from one measurement set.

Optical Coherence Tomography Angiography (OCTA) refers to a powerful class of OCT scanning protocols and algorithms that selectively enhance the imaging of blood vessel lumens, based mainly on the motion and scattering of red blood cells (RBCs). Though OCTA is widely used in clinical and basic science applications for visualization of perfused blood vessels, OCTA is still primarily a qualitative tool. However, more quantitative hemodynamic information would better delineate disease mechanisms, and potentially improve the sensitivity for detecting early stages of disease. Here, we take a broader view of OCTA in the context of microvascular hemodynamics and light scattering. Paying particular attention to the unique challenges presented by capillaries versus larger supplying and draining vessels, we critically assess opportunities and challenges in making OCTA a quantitative tool.

Blood flow patterns and kinetics in the choriocapillaris are poorly understood owing to a lack of quantitative ophthalmic imaging techniques for studying microvascular flow in the eye. Compared with the proximal retinal vasculature, the more distal choroidal vasculature is relatively more challenging to probe. Magnetic Resonance Imaging and Doppler Ultrasound can assess the retina and choroid, but do not resolve the finer layers or microvasculature. While Optical Coherence Tomography (OCT) angiography produces high-quality choroidal images, attempts at quantification through Doppler-based methods have had mixed success. Here, we use a new technique called Dynamic Contrast OCT (DyC-OCT), which tracks the passage of an intravascular scattering contrast agent, to reveal laminar blood flow patterns in the retina and choroid in vivo. While conceptually similar to fluorescence angiography, DyC-OCT has the substantial benefit of depth resolution, which enables separation of retinal and choroidal microvasculature. The scattering contrast agent enables improved angiography of both macro- and microvasculature in the retina and choroid. Blood plasma transit times are measured in individual vessels, while flow and volume are quantified for each of the microvascular layers. As expected, the choriocapillaris had the highest volume and flow. Blood flow rates were estimated with an average retinal blood flow of 9.1 ± 4.3 μL/min and an average choroidal blood flow of 40 ± 18.3 μL/min in the rat eye. These rates are consistent with previous literature. DyC-OCT affords a new perspective on the poorly understood choriocapillaris blood flow and kinetics and may be useful for studying outer retinal diseases.

The Western diet, causative in the development of atherosclerotic cardiovascular disease, has recently been associated with the development of diffuse white matter disease (WMD) and other subcortical changes. Yet, little is known about the pathophysiological mechanisms by which a high-fat diet can cause WMD. Mechanistic studies of deep brain regions in mice have been challenging due to a lack of non-invasive, high-resolution, and deep imaging technologies. Here we used Optical Coherence Tomography to study mouse cortical/subcortical structures noninvasively and in vivo. To better understand the role of Western Diet in the development of WMD, intensity and Doppler flow OCT images, obtained using a 1300 nm spectral / Fourier domain OCT system, were used to observe the structural and functional alterations in the cortex and corpus callosum of Western Diet and control diet mouse models. Specifically, we applied segmentation to the OCT images to identify the boundaries of the cortex/corpus callosum, and further quantify the layer thicknesses across animals between the two diet groups. Furthermore, microvasculature alterations such as changes in spatiotemporal flow profiles within diving arterioles, arteriole diameter, and collateral tortuosity were analyzed. In the current study, while the arteriole vessel diameters between the two diet groups was comparable, we show that collateral tortuosity was significantly higher in the Western diet group, compared to control diet group, possibly indicating remodeling of brain vasculature due to dietary changes. Moreover, there is evidence showing that the corpus callosum is thinner in Western diet mice, indicative of tissue atrophy.

Visible light is absorbed by intrinsic chromophores such as photopigment, melanin, and hemoglobin, and scattered by subcellular structures, all of which are potential retinal disease biomarkers. Recently, high-resolution quantitative measurement and mapping of hemoglobin concentrations was demonstrated using visible light Optical Coherence Tomography (OCT). Yet, most high-resolution visible light OCT systems adopt free-space, or bulk, optical setups, which could limit clinical applications. Here, the construction of a multi-functional fiber-optic OCT system for human retinal imaging with

In the original publication of the article the fifth author’s name “A. Littlewood” was submitted as “A. Littewood” which was left unnoticed in the later stages. The correct name is as published in this erratum.

In biological tissue, longer near-infrared wavelengths generally experience less scattering and more water absorption. Here we demonstrate an optical coherence tomography (OCT) system centered at 2.1 microns, whose bandwidth falls in the 2.2 micron water absorption optical window, for in vivo imaging of the rodent brain. We show in vivo that at 2.1 microns, the OCT signal is actually attenuated less in cranial bone than at 1.3 microns, and is also less susceptible to multiple scattering tails. We also show that the 2.2 micron window enables direct spectroscopic OCT assessment of tissue water content. We conclude that with further optimization, 2.2 micron OCT will have advantages in low-water-content tissue such as bone, as well as applications where extensive averaging is possible to compensate absorption losses.

We present a new optical modality called interferometric Near-Infrared Spectroscopy (iNIRS), which measures time-of-flight- (TOF-) resolved field autocorrelations in turbid media, enabling both optical and dynamical properties to be quantified. The iNIRS method is described, validated, and demonstrated in vivo in the brain.

The design of a multi-functional fiber-based Optical Coherence Tomography (OCT) system for human retinal imaging with < 2 micron axial resolution in tissue is described. A detailed noise characterization of two supercontinuum light sources with different pulse repetition rates is presented. The higher repetition rate and lower noise source is found to enable a sensitivity of 96 dB with 0.15 mW light power at the cornea and a 98 microsecond exposure time. Using a broadband (560 ± 50 nm), 90/10, fused single-mode fiber coupler designed for visible wavelengths, the sample arm is integrated into an ophthalmoscope platform, similar to current clinical OCT systems. To demonstrate the instrument's range of operation, in vivo structural retinal imaging is also shown at 0.15 mW exposure with 10,000 and 70,000 axial scans per second (the latter comparable to commercial OCT systems), and at 0.03 mW exposure and 10,000 axial scans per second (below maximum permissible continuous exposure levels). Lastly, in vivo spectroscopic imaging of anatomy, saturation, and hemoglobin content in the human retina is also demonstrated.

White Matter Disease is increasingly being recognized as an important cause of cognitive decline and dementia. Various investigations have linked chronic diet-related conditions to the development of white matter lesions, which appear as white matter hyperintensities on T2-weighted magnetic resonance imaging (MRI) scans of the brain. Thus, it can be postulated that the metabolic, inflammatory, and microvascular changes accompanying a western diet, hyperlipidemia, hypertension, and diabetes mellitus type II (DMII) are potential mediators in the development and progression of white matter disease, which in turn contributes to the development and progression of cognitive decline. This review will examine evidence for potential metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline. Specifically, we will focus on the effects of altered insulin signaling in diabetes, obesity-induced oxidative stress, neuroinflammation, arterial stiffness due to hypertension, ischemia secondary to cerebral small vessel disease, and blood brain barrier disturbances.

Despite the prevalence of optical imaging techniques to measure hemodynamics in large retinal vessels, quantitative measurements of retinal capillary and choroidal hemodynamics have traditionally been challenging. Here, a new imaging technique called dynamic contrast optical coherence tomography (DyC-OCT) is applied in the rat eye to study microvascular blood flow in individual retinal and choroidal layers in vivo. DyC-OCT is based on imaging the transit of an intravascular tracer dynamically as it passes through the field-of-view. Hemodynamic parameters can be determined through quantitative analysis of tracer kinetics. In addition to enabling depth-resolved transit time, volume, and flow measurements, the injected tracer also enhances OCT angiograms and enables clear visualization of the choriocapillaris, particularly when combined with a post-processing method for vessel enhancement. DyC-OCT complements conventional OCT angiography through quantification of tracer dynamics, similar to fluorescence angiography, but with the important added benefit of laminar resolution.

We introduce and implement interferometric near-infrared spectroscopy (iNIRS), which simultaneously extracts the optical and dynamic properties of turbid media from the analysis of the spectral interference fringe pattern. The spectral interference fringe pattern is measured using a Mach-Zehnder interferometer with a frequency swept narrow bandwidth light source such that the temporal intensity autocorrelations can be determined for all photon path lengths. This approach enables time-of-flight (TOF) resolved measurement of scatterer motion, which is a feature inaccessible in well-established diffuse correlation spectroscopy techniques. We prove this by analyzing intensity correlations of the light transmitted through diffusive fluid phantoms with photon random walks of up to 55 (approximately 110 scattering events) using laser sweep rates on the order of 100kHz. Thus, the results we present here advance diffuse optical methods by enabling simultaneous determination of depth-resolved optical properties and dynamics in highly scattering samples.

Introduction:Recently developed direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV) are groundbreaking in their high efficacy across disease genotypes and lack of severe side effects. This study used a cost-of-illness (COI) approach to estimate the net value conferred by one of these novel drug combinations, sofosbuvir and velpatasir (SOF/VEL), recently licensed for generic manufacture in India.Methods:This study considered COI from lifetime earnings lost due to disability and premature death from HCV infection. Risk of death and disability in future years was calculated using a Markov state-transition model with parameters determined from the literature. The future earnings of sampled patients were predicted using an empirical earnings model, with coefficients determined from India Human Development Survey data. Costs to both the patient and secondarily infected individuals were considered.Results:Preliminary results suggested that curing individuals diagnosed with chronic HCV in India would preserve INR 3.7 million (USD 55,750) in earnings per person. For non-cirrhotic (NC) and compensated cirrhotic (CC) individuals, the expected benefits associated with preventing secondary infections were worth between one and forty-one percent of the value of benefits conferred to the diagnosed individuals (depending on sex and extent of liver damage). Treating decompensated cirrhotic (DC) individuals with DAAs alone offered minimal earnings benefits because these individuals will likely remain disabled and unable to work without a liver transplant. Expected net benefits of treatment were substantial for NC and CC patients, ranging from INR 640,349 (USD 9,531) for NC women to INR 10.7 million (USD 158,968) for CC men. The cost of treatment for DC individuals exceeded the expected earnings benefits.Conclusions:For average NC and CC individuals, the cost of treatment with SOF/VEL is offset by the benefits of increased future productivity. Increased earnings are not sufficient to offset the cost of treatment for DC individuals, but treatment may still be justified on the basis of the intrinsic value of health improvements and other treatment benefits.

In vivo optical microscopic imaging techniques have recently emerged as important tools for the study of neurobiological development and pathophysiology. In particular, two-photon microscopy has proved to be a robust and highly flexible method for in vivo imaging in highly scattering tissue. However, two-photon imaging typically requires extrinsic dyes or contrast agents, and imaging depths are limited to a few hundred microns. Here we demonstrate Optical Coherence Microscopy (OCM) for in vivo imaging of neuronal cell bodies and cortical myelination up to depths of ~1.3 mm in the rat neocortex. Imaging does not require the administration of exogenous dyes or contrast agents, and is achieved through intrinsic scattering contrast and image processing alone. Furthermore, using OCM we demonstrate in vivo, quantitative measurements of optical properties (index of refraction and attenuation coefficient) in the cortex, and correlate these properties with laminar cellular architecture determined from the images. Lastly, we show that OCM enables direct visualization of cellular changes during cell depolarization and may therefore provide novel optical markers of cell viability.

Cortical spreading depression (CSD) is associated with severe hypoperfusion in mice. Using minimally invasive multimodal optical imaging, we show that severe flow reductions during and after spreading depression are associated with a steep decline in cerebral metabolic rate of oxygen. Concurrent severe hemoglobin desaturation suggests that the oxygen metabolism becomes at least in part supply limited, and the decrease in cortical blood volume implicates vasoconstriction as the mechanism. In support of oxygen supply-demand mismatch, cortical nicotinamide adenine dinucleotide (NADH) fluorescence increases during spreading depression for at least 5 minutes, particularly away from parenchymal arterioles. However, modeling of tissue oxygen delivery shows that cerebral metabolic rate of oxygen drops more than predicted by a purely supply-limited model, raising the possibility of a concurrent reduction in oxygen demand during spreading depression. Importantly, a subsequent spreading depression triggered within 15 minutes evokes a monophasic flow increase superimposed on the oligemic baseline, which markedly differs from the response to the preceding spreading depression triggered in naive cortex. Altogether, these data suggest that CSD is associated with long-lasting oxygen supply-demand mismatch linked to severe vasoconstriction in mice.

Cardiac and respiratory motions in animals are the primary source of image quality degradation in dynamic imaging studies, especially when using phase-resolved imaging modalities such as spectral-domain optical coherence tomography (SD-OCT), whose phase signal is very sensitive to movements of the sample. This study demonstrates a method with which to compensate for motion artifacts in dynamic SD-OCT imaging of the rodent cerebral cortex. We observed that respiratory and cardiac motions mainly caused, respectively, bulk image shifts (BISs) and global phase fluctuations (GPFs). A cross-correlation maximization-based shift correction algorithm was effective in suppressing BISs, while GPFs were significantly reduced by removing axial and lateral global phase variations. In addition, a non-origin-centered GPF correction algorithm was examined. Several combinations of these algorithms were tested to find an optimized approach that improved image stability from 0.5 to 0.8 in terms of the cross-correlation over 4 s of dynamic imaging, and reduced phase noise by two orders of magnitude in ~8% voxels.

In vivoimaging of cerebral tissue oxygenation is important in defining healthy physiology and pathological departures associated with cerebral disease. We used a recently developed two-photon microscopy method, based on a novel phosphorescent nanoprobe, to image tissue oxygenation in the rat primary sensory cortex in response to sensory stimulation. Our measurements showed that a stimulus-evoked increase in tissue pO2depended on the baseline pO2level. In particular, during sustained stimulation, the steady-state pO2at low-baseline locations remained at the baseline, despite large pO2increases elsewhere. In contrast to the steady state, where pO2never decreased below the baseline, transient decreases occurred during the “initial dip” and “poststimulus undershoot.” These results suggest that the increase in blood oxygenation during the hemodynamic response, which has been perceived as a paradox, may serve to prevent a sustained oxygenation drop at tissue locations that are remote from the vascular feeding sources.

Measurements of oxygen partial pressure (pO(2)) with high temporal and spatial resolution in three dimensions is crucial for understanding oxygen delivery and consumption in normal and diseased brain. Among existing pO(2) measurement methods, phosphorescence quenching is optimally suited for the task. However, previous attempts to couple phosphorescence with two-photon laser scanning microscopy have faced substantial difficulties because of extremely low two-photon absorption cross-sections of conventional phosphorescent probes. Here we report to our knowledge the first practical in vivo two-photon high-resolution pO(2) measurements in small rodents' cortical microvasculature and tissue, made possible by combining an optimized imaging system with a two-photon-enhanced phosphorescent nanoprobe. The method features a measurement depth of up to 250 microm, sub-second temporal resolution and requires low probe concentration. The properties of the probe allowed for direct high-resolution measurement of cortical extravascular (tissue) pO(2), opening many possibilities for functional metabolic brain studies.

Author Manuscript 2011 February 1., Purpose: The purpose of this study was to report normal macular thickness measurements and assess reproducibility of retinal thickness measurements acquired by a time-domain optical coherence tomography (OCT) (Stratus, Carl Zeiss Meditec, Inc., Dublin, CA) and three commercially available spectral/Fourier domain OCT instruments (Cirrus HD-OCT, Carl Zeiss Meditec, Inc.; RTVue-100, Optovue, Inc., Fremont, CA; 3D OCT-1000, Topcon, Inc., Paramus, NJ). Methods: Forty randomly selected eyes of 40 normal, healthy volunteers were imaged. Subjects were scanned twice during 1 visit and a subset of 25 was scanned again within 8 weeks. Retinal thickness measurements were automatically generated by OCT software and recorded after manual correction. Regression and Bland-Altman plots were used to compare agreement between instruments. Reproducibility was analyzed by using intraclass correlation coefficients, and incidence of artifacts was determined. Results: Macular thickness measurements were found to have high reproducibility across all instruments with intraclass correlation coefficients values ranging 84.8% to 94.9% for Stratus OCT, 92.6% to 97.3% for Cirrus Cube, 76.4% to 93.7% for RTVue MM5, 61.1% to 96.8% for MM6, 93.1% to 97.9% for 3D OCT-1000 radial, and 31.5% to 97.5% for 3D macular scans. Incidence of artifacts was higher in spectral/Fourier domain instruments, ranging from 28.75% to 53.16%, compared with 17.46% in Stratus OCT. No significant age or sex trends were found in the measurements. Conclusion: Commercial spectral/Fourier domain OCT instruments provide higher speed and axial resolution than the Stratus OCT, although they vary greatly in scanning protocols and are currently limited in their analysis functions. Further development of segmentation algorithms and quantitative features are needed to assist clinicians in objective use of these newer instruments to manage diseases., National Institutes of Health (U.S.) (Contract RO1-EY11289-23), National Institutes of Health (U.S.) (Contract R01-EY13178-07), National Institutes of Health (U.S.) (Contract P30-EY008098), United States. Air Force Office of Scientific Research (FA9550-07-1-0101), United States. Air Force Office of Scientific Research (FA9550-07-1-0014)

Objective To evaluate intraretinal anatomy in patients with exudative age-related macular degeneration (AMD) using high-speed ultrahigh resolution optical coherence tomography (hsUHR-OCT) before and 1 month after intravitreal injection of ranibizumab. Design Retrospective case series. Participants Twelve eyes of 12 patients. Methods A broad bandwidth superluminescent diode laser light source and spectral/Fourier domain signal detection were used to create a prototype hsUHR-OCT instrument with 3.5 μm axial image resolution and approximately 25,000 lines/second acquisition speed. Twelve eyes of 12 patients with exudative AMD were imaged with hsUHR-OCT before and 1 month after intravitreal ranibizumab injection. High pixel density and raster-scanned 3-dimensional (3D) OCT data sets were generated. Three-dimensional imaging software was used to calculate subretinal/retinal pigment epithelium fluid volume and volume of the fibrovascular lesion. Main Outcome Measures Qualitative and quantitative analysis of hsUHR-OCT images and 3D data sets. Results All eyes had some degree of normalization of macular contour after intravitreal ranibizumab. The inner/outer photoreceptor segment junction visualized on hsUHR-OCT was discontinuous, overlying the fibrovascular lesion in all 12 of 12 eyes both before and after treatment; 9 of 12 eyes had focal areas of thinning of the outer nuclear layer, which remained after treatment. Volumetric measurements were possible in 8 of 12 eyes with 3D-rendering software. Fibrovascular lesion volume did not change significantly after treatment. Conclusions hsUHR-OCT is capable of unprecedented imaging speed and resolution, making it a valuable instrument in measuring in vivo intraretinal pathology. All 12 eyes had some normalization of macular contour. Fibrovascular lesion volume did not change significantly 1 month after treatment, suggesting that ranibizumab does not cause much initial regression of preexisting neovascular tissue. Photoreceptor abnormalities remained in all patients after treatment of wet AMD, suggesting that although ranibizumab improves overall retinal architecture, some photoreceptor damage may be irreversible. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Aims: To demonstrate ultrahigh-resolution, three-dimensional optical coherence tomography (3D-OCT) and projection OCT fundus imaging for enhanced visualisation of outer retinal pathology in non-exudative age-related macular degeneration (AMD). Methods: A high-speed, 3.5 μm resolution OCT prototype instrument was developed for the ophthalmic clinic. Eighty-three patients with non-exudative AMD were imaged. Projection OCT fundus images were generated from 3D-OCT data by selectively summing different retinal depth levels. Results were compared with standard ophthalmic examination, including fundus photography and fluorescein angiography, when indicated. Results: Projection OCT fundus imaging enhanced the visualisation of outer retinal pathology in non-exudative AMD. Different types of drusen exhibited distinct features in projection OCT images. Photoreceptor disruption was indicated by loss of the photoreceptor inner/outer segment (IS/OS) boundary and external limiting membrane (ELM). RPE atrophy can be assessed using choroid-level projection OCT images. Conclusions: Projection OCT fundus imaging facilities rapid interpretation of large 3D-OCT data sets. Projection OCT enhances contrast and visualises outer retinal pathology not visible with standard fundus imaging or OCT fundus imaging. Projection OCT fundus images enable registration with standard ophthalmic diagnostics and cross-sectional OCT images. Outer retinal alterations can be assessed and drusen morphology, photoreceptor impairment and pigmentary abnormalities identified.

We introduce and implement interferometric near-infrared spectroscopy (iNIRS), which simultaneously extracts optical and dynamical properties of turbid media through analysis of a spectral interference fringe pattern. The spectral interference fringe pattern is measured using a Mach-Zehnder interferometer with a frequency-swept narrow linewidth laser. Fourier analysis of the detected signal is used to determine time-of-flight (TOF)-resolved intensity, which is then analyzed over time to yield TOF-resolved intensity autocorrelations. This approach enables quantification of optical properties, which is not possible in conventional, continuous-wave near-infrared spectroscopy (NIRS). Furthermore, iNIRS quantifies scatterer motion based on TOF-resolved autocorrelations, which is a feature inaccessible by well-established diffuse correlation spectroscopy (DCS) techniques. We prove this by determining TOF-resolved intensity and temporal autocorrelations for light transmitted through diffusive fluid phantoms with optical thicknesses of up to 55 reduced mean free paths (approximately 120 scattering events). The TOF-resolved intensity is used to determine optical properties with time-resolved diffusion theory, while the TOF-resolved intensity autocorrelations are used to determine dynamics with diffusing wave spectroscopy. iNIRS advances the capabilities of diffuse optical methods and is suitable for in vivo tissue characterization. Moreover, iNIRS combines NIRS and DCS capabilities into a single modality.

We present advances in deep rodent brain imaging using Optical Coherence Tomography: including dynamic contrast, ~1700 nm for deeper penetration to subcortical layers, and visible light for hemoglobin concentrations and cortical metabolism.

Excessive retinal vascular permeability contributes to the pathogenesis of proliferative diabetic retinopathy and diabetic macular edema, leading causes of vision loss in working-age adults. Using mass spectroscopy–based proteomics, we detected 117 proteins in human vitreous and elevated levels of extracellular carbonic anhydrase-I (CA-I) in vitreous from individuals with diabetic retinopathy, suggesting that retinal hemorrhage and erythrocyte lysis contribute to the diabetic vitreous proteome. Intravitreous injection of CA-I in rats increased retinal vessel leakage and caused intraretinal edema. CA-I–induced alkalinization of vitreous increased kallikrein activity and its generation of factor XIIa, revealing a new pathway for contact system activation. CA-I–induced retinal edema was decreased by complement 1 inhibitor, neutralizing antibody to prekallikrein and bradykinin receptor antagonism. Subdural infusion of CA-I in rats induced cerebral vascular permeability, suggesting that extracellular CA-I could have broad relevance to neurovascular edema. Inhibition of extracellular CA-I and kallikrein-mediated innate inflammation could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema. The effects of diabetes in the eye are characterized by microvascular abnormalities, proliferation of retinal vessels and increased retinal vascular permeability (RVP), which contributes to nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME), respectively. Among working-age adults in developed countries, PDR and DME are the leading causes of severe and moderate vision loss 1,2 . Although the incidence and progression of diabetic retinopathy can be reduced by intensive glycemic and blood pressure control 3–5 , nearly

A 42-year-old man with Hunter syndrome developed bilateral visual field loss. Visual field testing demonstrated bilateral ring scotomata that corresponded to areas of thinning seen on standard resolution optical coherence tomography. High-speed, ultrahigh resolution optical coherence tomography, capable of 3.5-micron axial resolution, showed a loss of photoreceptors outside the fovea and cystoid spaces within the inner nuclear, ganglion cell, and outer nuclear layers. These results were consistent with histopathologic features that have been reported previously in patients with Hunter syndrome. Optical coherence tomography could be used as a diagnostic modality to monitor patients with Hunter syndrome and to detect subclinical forms of disease. [Ophthalmic Surg Lasers Imaging 2007;38:423-428.] AUTHORS From New England Eye Center (MKY, RWC, TRH, IG, MW, JSD), Tufts-New England Medical Center, Tufts University, Boston, Massachusetts; the Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics (VJS, IG, JGF, MW), Massachusetts Institute of Technology, Cambridge, Massachusetts; and UPMC Eye Center and the Eye and Ear Institute (JSS), Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Accepted for publication April 20, 2007. Supported in part by National Institutes of Health RO1-EY13178-06, RO1-EY11289-20, P30-EY08098, P30-EY13078, Air Force Office of Scientific Research, Medical Free Electron Laser Program contract FA9550-040- 1-0046, FA9550-040-1-0011, National Science Foundation ECS-0119452, BES-0522845, The Eye and Ear Foundation (Pittsburgh, PA), and Research to Prevent Blindness Unrestricted Grant and Medical Student Eye Research Fellowship. Drs. Fujimoto and Schuman receive royalties from intellectual property licensed by the Massachusetts Institute of Technology to Carl Zeiss Meditec, and Drs. Duker and Schuman receive research support from Optovue, Inc. Dr. Schuman also receives research support from Alcon Laboratories, Inc., Allergan, Inc., SOLX, and Clarity, and receives lecture fees from Alcon Laboratories, Inc., Allergan, Inc., Carl Zeiss Meditec, Merck U.S. Human Health, the National Eye Institute, Heidelberg Engineering, Inc., and Optovue, Inc. Dr. Schuman did not participate in the editorial review of this manuscript. Address correspondence to Thomas R. Hedges III, MD, Ophthalmology Department, Tufts-New England Medical Center, 750 Washington Street, Boston, MA 02111.

Improving our understanding of brain function requires novel tools to observe multiple physiological parameters with high resolution in vivo. We have developed a multimodal imaging system for investigating multiple facets of cerebral blood flow and metabolism in small animals. The system was custom designed and features multiple optical imaging capabilities, including 2-photon and confocal lifetime microscopy, optical coherence tomography, laser speckle imaging, and optical intrinsic signal imaging. Here, we provide details of the system's design and present in vivo observations of multiple metrics of cerebral oxygen delivery and energy metabolism, including oxygen partial pressure, microvascular blood flow, and NADH autofluorescence.

A spectral/Fourier domain optical coherence tomography (OCT) intravital microscope using a supercontinuum light source at 1.7μm was developed to study subcortical structures noninvasively in the living mouse brain. The benefits of 1.7μm for deep tissue brain imaging are demonstrated by quantitatively comparing OCT signal attenuation characteristics of cortical tissue across visible and near-infrared wavelengths. Imaging of hippocampal tissue architecture and white matter microvasculature are demonstrated in vivo through thinned-skull, glass coverslip-reinforced cranial windows in mice. Applications of this novel platform include monitoring disease progression and pathophysiology in rodent models of Alzheimer's disease and subcortical dementias, including vascular dementia.

Although microvascular dysfunction accompanies cognitive decline in aging, vascular dementia, and Alzheimer's disease, tools to study microvasculature longitudinally in vivo are lacking. Here, we use Doppler optical coherence tomography (OCT) and angiography for noninvasive, longitudinal imaging of mice with chronic cerebral hypoperfusion for up to 1 month. In particular, we optimized the OCT angiography method to selectively image red blood cell (RBC)-perfused capillaries, leading to a novel way of assessing capillary supply heterogeneity in vivo. After bilateral common carotid artery stenosis (BCAS), cortical blood flow measured by Doppler OCT dropped to half of baseline throughout the imaged tissue acutely. Microscopic imaging of the capillary bed with OCT angiography further revealed local heterogeneities in cortical flow supply during hypoperfusion. The number of RBC-perfused capillaries decreased, leading to increased oxygen diffusion distances in the days immediately after BCAS. Linear regression showed that RBC-perfused capillary density declined by 0.3% for a drop in flow of 1 mL/100 g per minute, and decreases in RBC-perfused capillary density as high as 25% were observed. Taken together, these results demonstrate the existence of local supply heterogeneity at the capillary level even at nonischemic global flow levels, and demonstrate a novel imaging method to assess this heterogeneity.

The transit time distribution of blood through the cerebral microvasculature both constrains oxygen delivery and governs the kinetics of neuroimaging signals such as blood-oxygen-level-dependent functional Magnetic Resonance Imaging (BOLD fMRI). However, in spite of its importance, capillary transit time distribution has been challenging to quantify comprehensively and efficiently at the microscopic level. Here, we introduce a method, called Dynamic Contrast Optical Coherence Tomography (DyC-OCT), based on dynamic cross-sectional OCT imaging of an intravascular tracer as it passes through the field-of-view. Quantitative transit time metrics are derived from temporal analysis of the dynamic scattering signal, closely related to tracer concentration. Since DyC-OCT does not require calibration of the optical focus, quantitative accuracy is achieved even deep in highly scattering brain tissue where the focal spot degrades. After direct validation of DyC-OCT against dilution curves measured using a fluorescent plasma label in surface pial vessels, we used DyC-OCT to investigate the transit time distribution in microvasculature across the entire depth of the mouse somatosensory cortex. Laminar trends were identified, with earlier transit times and less heterogeneity in the middle cortical layers. The early transit times in the middle cortical layers may explain, at least in part, the early BOLD fMRI onset times observed in these layers. The layer-dependencies in heterogeneity may help explain how a single vascular supply manages to deliver oxygen to individual cortical layers with diverse metabolic needs.

A method of measuring cortical oxygen metabolism in the mouse brain that uses independent quantitative measurements of three key parameters: cerebral blood flow (CBF), arteriovenous oxygen extraction (OE), and hemoglobin concentration ([HbT]) is presented. Measurements were performed using a single visible light spectral/Fourier domain OCT microscope, with Doppler and spectroscopic capabilities, through a thinned-skull cranial window in the mouse brain. Baseline metabolic measurements in mice are shown to be consistent with literature values. Oxygen consumption, as measured by this method, did not change substantially during minor changes either in the fraction of inspired oxygen (FiO2) or in the fraction of inspired carbon dioxide (FiCO2), in spite of larger variations in oxygen saturations. This set of experiments supports, but does not prove, the validity of the proposed method of measuring brain oxygen metabolism.

Using a full-field optical coherence tomography system, we measured changes in the time that light requires to pass through photoreceptor outer segments, when the retina is stimulated by a light pulse. This effect can be used to monitor the activity of single cones in the living human eye. Objective monitoring of photoreceptor activity using such intrinsic optical signals could have important diagnostic applications in ophthalmology and neurology and might provide insight to facilitate basic research.

Interferometric near-infrared spectroscopy (iNIRS) is a time-of-flight- (TOF-) resolved sensing modality for determining optical and dynamical properties of a turbid medium. iNIRS achieves this by measuring the interference spectrum of light traversing the medium with a rapidly tunable, or frequency-swept, light source. Thus, iNIRS system performance critically depends on the source and detection apparatus. Using a current-tuned 855 nm distributed feedback laser as the source, we experimentally characterize iNIRS system parameters, including speed, sensitivity, dynamic range, TOF resolution, and TOF range. We also employ a novel Mach-Zehnder interferometer variant with a multi-pass loop to monitor the laser instantaneous linewidth and TOF range at high tuning speeds. We identify and investigate tradeoffs between parameters, with the goal of optimizing performance. We also demonstrate a technique to combine forward and backward sweeps to double the effective speed. Combining these advances, we present in vivo TPSFs and autocorrelations from the mouse brain with TOF resolutions of 22-60 ps, 36-47 dB peak-sidelobe dynamic range, 4-10 μs autocorrelation lag time resolution, a TOF range of nanoseconds or more, and nearly shot noise limited sensitivity.

Recent hardware advances in optical coherence tomography (OCT) have led to ever higher A-scan rates. However, the estimation of blood flow axial velocities is limited by the presence and type of noise. Higher acquisition rates alone do not necessarily enable precise quantification of Doppler velocities, particularly if the estimator is suboptimal. In previous work, we have shown that the Kasai autocorrelation estimator is statistically suboptimal under conditions of additive white Gaussian noise. In addition, for practical OCT measurements of flow, decorrelation noise affects Doppler frequency estimation by broadening the signal spectrum. Here, we derive a general maximum likelihood estimator (MLE) for Doppler frequency estimation that takes into account additive white noise as well as signal decorrelation. We compare the decorrelation MLE with existing techniques using simulated and flow phantom data and find that it has better performance, achieving the Cramer-Rao lower bound. By making an approximation, we also provide an interpretation of this method in the Fourier domain. We anticipate that this estimator will be particularly suited for estimating blood flow in in vivo scenarios.

A recent trend in optical coherence tomography (OCT) hardware has been the move towards higher A-scan rates. However, the estimation of axial blood flow velocities is affected by the presence and type of noise, as well as the estimation method. Higher acquisition rates alone do not enable the accurate quantification of axial blood velocity. Moreover, decorrelation is an unavoidable feature of OCT signals when there is motion relative to the OCT beam. For in-vivo OCT measurements of blood flow, decorrelation noise affects Doppler frequency estimation by broadening the signal spectrum. Here we derive a maximum likelihood estimator (MLE) for Doppler frequency estimation that takes into account spectral broadening due to decorrelation. We compare this estimator with existing techniques. Both theory and experiment show that this estimator is effective, and outperforms the Kasai and additive white Gaussian noise (AWGN) ML estimators. We find that maximum likelihood estimation can be useful for estimating Doppler shifts for slow axial flow and near transverse flow. Due to the inherent linear relationship between decorrelation and Doppler shift of scatterers moving relative to an OCT beam, decorrelation itself may be a measure of flow speed.

Here, we present high-speed spectral domain OCT in the visible spectral range using a supercontinuum source that performs angiography, oximetry, and speed assessment of red blood cells in individual vessels of the mouse pinna in vivo.