1. Articles from Vivek J. Srinivasan

    1-24 of 54 1 2 3 »
    1. Incoherent excess noise spectrally encodes broadband light sources

      Incoherent excess noise spectrally encodes broadband light sources

      Across optics and photonics, excess intensity noise is often considered a liability. Here, we show that excess noise in broadband supercontinuum and superluminescent diode light sources encodes each spectral channel with unique intensity fluctuations, which actually serve a useful purpose. Specifically, we report that excess noise correlations can both characterize the spectral resolution of spectrometers and enable cross-calibration of their wavelengths across a broad bandwidth. Relative to previous methods that use broadband interferometry and narrow linewidth lasers to characterize and calibrate spectrometers, our approach is simple, comprehensive, and rapid enough to be deployed during spectrometer alignment. First, we employ this ...

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    2. Water wavenumber calibration for visible light optical coherence tomography

      Water wavenumber calibration for visible light optical coherence tomography

      Significance : Visible light optical coherence tomography (OCT) is emerging for spectroscopic and ultrahigh resolution imaging, but challenges remain. Depth-dependent dispersion limits retinal image quality and current correction approaches are cumbersome. Inconsistent group refractive indices during image reconstruction also limit reproducibility. Aim: To introduce and evaluate water wavenumber calibration (WWC), which corrects depth-dependent dispersion and provides an accurate depth axis in water. Approach: Enabled by a visible light OCT spectrometer configuration with a 3- to 4-dB sensitivity roll-off over 1 mm in air across a 90-nm bandwidth, we determine the spectral phase of a 1-mm water cell, an affine function of ...

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    3. Visibility of microvessels in Optical Coherence Tomography Angiography depends on angular orientation

      Visibility of microvessels in Optical Coherence Tomography Angiography depends on angular orientation

      OCT Angiography (OCTA) is a widespread tool for depth‐resolved imaging of chorioretinal vasculature with single microvessel resolution. To improve the clinical interpretation of OCTA, the conditions affecting visualization of microvessels must be defined. Here we inject a scattering plasma tracer (Intralipid) during OCTA imaging of the anesthetized rat eye. In the retina, we find that interlaminar (vertical) vessels that connect laminae have one‐fourth to one‐third the OCTA red blood cell to tracer (RBC‐to‐tracer) signal ratio of intralaminar (horizontal) vessels. This finding suggests that the OCTA signal from microvessels depends on angular orientation, making vertically‐oriented ...

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    4. Noninvasive, in vivo rodent brain optical coherence tomography at 2.1  microns

      Noninvasive, in vivo rodent brain optical coherence tomography at 2.1  microns

      n 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 ...

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    5. Dynamic Contrast Optical Coherence Tomography reveals laminar microvascular hemodynamics in the mouse neocortex in vivo

      Dynamic Contrast Optical Coherence Tomography reveals laminar microvascular hemodynamics in the mouse neocortex in vivo

      Studies of flow-metabolism coupling often presume that microvessel architecture is a surrogate for blood flow. To test this assumption, we introduce an in vivo Dynamic Contrast Optical Coherence Tomography (DyC-OCT) method to quantify layer-resolved microvascular blood flow and volume across the full depth of the mouse neocortex, where the angioarchitecture has been previously described . First, we cross-validate average DyC-OCT cortical flow against conventional Doppler OCT flow. Next, with laminar DyC-OCT, we discover that layer 4 consistently exhibits the highest microvascular blood flow, approximately two-fold higher than the outer cortical layers. While flow differences between layers are well-explained by microvascular volume ...

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    6. Compensating spatially dependent dispersion in visible light OCT

      Compensating spatially dependent dispersion in visible light OCT

      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 109 nm bandwidth visible light OCT mouse retinal imaging system centered at 587 nm. After carefully compensating ...

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    7. Visible light optical coherence microscopy imaging of the mouse cortex with femtoliter volume resolution

      Visible light optical coherence microscopy imaging of the mouse cortex with femtoliter volume resolution

      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/e 2 intensity diameter ~0.82 Airy disks), enabling ~1.1 ...

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    8. Structural and functional human retinal imaging with a fiber-based visible light OCT ophthalmoscope

      Structural and functional human retinal imaging with a fiber-based visible light OCT ophthalmoscope

      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 ...

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    9. Dynamic contrast optical coherence tomography images transit time and quantifies microvascular plasma volume and flow in the retina and choriocapillaris

      Dynamic contrast optical coherence tomography images transit time and quantifies microvascular plasma volume and flow in the retina and choriocapillaris

      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 ...

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    10. Microstructural characterization of myocardial infarction with optical coherence tractography and two‐photon microscopy

      Microstructural characterization of myocardial infarction with optical coherence tractography and two‐photon microscopy

      Myocardial infarction leads to complex changes in the fiber architecture of the heart. Here, we present a novel optical approach to characterize these changes in intact hearts in three dimensions. Optical coherence tomography (OCT) was used to derive a depth‐resolved field of orientation on which tractography was performed. Tractography of healthy myocardium revealed a smooth linear transition in fiber inclination or helix angle from the epicardium to endocardium. Conversely, in infarcted hearts, no coherent microstructure could be identified in the infarct with OCT. Additional characterization of the infarct was performed by the measurement of light attenuation and with two ...

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    11. Imaging and graphing of cortical vasculature using dynamically focused optical coherence microscopy angiography

      Imaging and graphing of cortical vasculature using dynamically focused optical coherence microscopy angiography

      Recently, optical coherence tomography (OCT) angiography has enabled label-free imaging of vasculature based on dynamic scattering in vessels. However, quantitative volumetric analysis of the vascular networks depicted in OCT angiography data has remained challenging. Multiple-scattering tails (artifacts specific to the imaging geometry) make automated assessment of vascular morphology problematic. We demonstrate that dynamically focused optical coherence microscopy (OCM) angiography with a high numerical aperture, chosen so the scattering length greatly exceeds the depth-of-field, significantly reduces the deleterious effect of multiple-scattering tails in synthesized angiograms. Capitalizing on the improved vascular image quality, we devised and tailored a self-correcting automated graphing approach ...

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    12. Noninvasive, in vivo imaging of subcortical mouse brain regions with 1.7  μm optical coherence tomography

      Noninvasive, in vivo imaging of subcortical mouse brain regions with 1.7  μm optical coherence tomography

      A spectral/Fourier domain optical coherence tomography (OCT) intravital microscope using a supercontinuum light source at 1.7 μm was developed to study subcortical structures noninvasively in the living mouse brain. The benefits of 1.7 μm 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 ...

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    13. Laminar microvascular transit time distribution in the mouse somatosensory cortex revealed by Dynamic Contrast Optical Coherence Tomography

      Laminar microvascular transit time distribution in the mouse somatosensory cortex revealed by Dynamic Contrast Optical Coherence Tomography

      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 ...

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    14. Cerebral metabolic rate of oxygen (CMRO2) assessed by combined Doppler and spectroscopic OCT

      Cerebral metabolic rate of oxygen (CMRO2) assessed by combined Doppler and spectroscopic OCT

      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 (FiO 2 ) or in the ...

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    15. Mapping the 3D Connectivity of the Rat Inner Retinal Vascular Network Using OCT Angiography

      Mapping the 3D Connectivity of the Rat Inner Retinal Vascular Network Using OCT Angiography

      Purpose : The purpose of this study is to demonstrate three-dimensional (3D) graphing based on optical coherence tomography (OCT) angiography for characterization of the inner retinal vascular architecture and determination of its topologic principles. Methods : Rat eyes ( N = 3) were imaged with a 1300-nm spectral/Fourier domain OCT microscope. A topologic model of the inner retinal vascular network was obtained from OCT angiography data using a combination of automated and manually-guided image processing techniques. Using a resistive network model, with experimentally-quantified flow in major retinal vessels near the optic nerve head as boundary conditions, theoretical changes in the distribution of flow ...

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    16. Micro-heterogeneity of flow in a mouse model of chronic cerebral hypoperfusion revealed by longitudinal Doppler optical coherence tomography and angiography

      Micro-heterogeneity of flow in a mouse model of chronic cerebral hypoperfusion revealed by longitudinal Doppler optical coherence tomography and angiography

      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 ...

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    17. Quantitative microvascular hemoglobin mapping using visible light spectroscopic Optical Coherence Tomography

      Quantitative microvascular hemoglobin mapping using visible light spectroscopic Optical Coherence Tomography

      Quantification of chromophore concentrations in reflectance mode remains a major challenge for biomedical optics. Spectroscopic Optical Coherence Tomography (SOCT) provides depth-resolved spectroscopic information necessary for quantitative analysis of chromophores, like hemoglobin, but conventional SOCT analysis methods are applicable only to well-defined specular reflections, which may be absent in highly scattering biological tissue. Here, by fitting of the dynamic scattering signal spectrum in the OCT angiogram using a forward model of light propagation, we quantitatively determine hemoglobin concentrations directly. Importantly, this methodology enables mapping of both oxygen saturation and total hemoglobin concentration, or alternatively, oxyhemoglobin and deoxyhemoglobin concentration, simultaneously. Quantification was ...

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    18. Feature Of The Week 9/14/14: UC Davis Investigates Brain Imaging with Optical Coherence Tomography

      Feature Of The Week 9/14/14: UC Davis Investigates Brain Imaging with Optical Coherence Tomography

      One of the nine high priority research areas in the recent BRAIN Initiative (executive summary available at HERE ) is to “Delineate mechanisms underlying human brain imaging technologies.” While empowering tools such as two-photon microscopy, used in conjunction with dyes and indicators, can image cellular and vascular activity, even measuring activity in all cells and vessels comprising a single voxel in a functional magnetic resonance imaging (fMRI) scanner remains a daunting task. Hence, mesoscopic imaging tools are needed to help bridge the gap between microscopic and macroscopic (human brain level) findings. Here, using Optical Coherence Tomography angiography at 1300 nm, we ...

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    19. Optical Coherence Tomography angiography reveals laminar microvascular hemodynamics in the rat somatosensory cortex during activation

      Optical Coherence Tomography angiography reveals laminar microvascular hemodynamics in the rat somatosensory cortex during activation

      The BOLD (blood-oxygen-level dependent) fMRI (functional Magnetic Resonance Imaging) signal is shaped, in part, by changes in red blood cell (RBC) content and flow across vascular compartments over time. These complex dynamics have been challenging to characterize directly due to a lack of appropriate imaging modalities. In this study, making use of infrared light scattering from RBCs, depth-resolved Optical Coherence Tomography (OCT) angiography was applied to image laminar functional hyperemia in the rat somatosensory cortex. After defining and validating depth-specific metrics for changes in RBC content and speed, laminar hemodynamic responses in microvasculature up to cortical depths of > 1 mm ...

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    20. Maximum Likelihood Doppler Frequency Estimation under Decorrelation Noise for Quantifying Flow in Optical Coherence Tomography

      Maximum Likelihood Doppler Frequency Estimation under Decorrelation Noise for Quantifying Flow in Optical Coherence Tomography

      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 sub-optimal. In previous work, we have shown that the Kasai autocorrelation estimator is statistically sub-optimal 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 ...

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    21. Feature Of The Week 10/20/13: Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

      Feature Of The Week 10/20/13: Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

      To better understand pathophysiology during brain injuries such as stroke, we combined a number of OCT imaging techniques. Namely, we employed Doppler methods to map blood flow, angiography methods to measure capillary-level perfusion and vessel diameter, and scattering quantification methods to determine cell viability. This multi-parametric approach was used to perform imaging in the acute and recovery stages in experimental ischemic stroke, with the goal of determining the fate of the penumbra using imaging biomarkers. The penumbra is an area of brain tissue which is compromised during stroke but could be salvaged through thrombolysis or other treatment methods. Multi-parametric imaging ...

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    22. Volumetric imaging and quantification of cytoarchitecture and myeloarchitecture with intrinsic scattering contrast

      Volumetric imaging and quantification of cytoarchitecture and myeloarchitecture with intrinsic scattering contrast

      We present volumetric imaging and computational techniques to quantify neuronal and myelin architecture with intrinsic scattering contrast. Using spectral / Fourier domain Optical Coherence Microscopy (OCM) and software focus-tracking we validate imaging of neuronal cytoarchitecture and demonstrate quantification in the rodent cortex in vivo . Additionally, by ex vivo imaging in conjunction with optical clearing techniques, we demonstrate that intrinsic scattering contrast is preserved in the brain, even after sacrifice and fixation. We volumetrically image cytoarchitecture and myeloarchitecture ex vivo across the entire depth of the rodent cortex. Cellular-level imaging up to the working distance of our objective (~3 mm) is demonstrated ...

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    23. Multiparametric optical coherence tomography imaging of the inner retinal hemodynamic response to visual stimulation

      Multiparametric optical coherence tomography imaging of the inner retinal hemodynamic response to visual stimulation

      The hemodynamic response to neuronal activation is a well-studied phenomenon in the brain, due to the prevalence of functional magnetic resonance imaging. The retina represents an optically accessible platform for studying lamina-specific neurovascular coupling in the central nervous system; however, due to methodological limitations, this has been challenging to date. We demonstrate techniques for the imaging of visual stimulus-evoked hyperemia in the rat inner retina using Doppler optical coherence tomography (OCT) and OCT angiography. Volumetric imaging with three-dimensional motion correction, en face flow calculation, and normalization of dynamic signal to static signal are techniques that reduce spurious changes caused by ...

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    24. Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

      Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

      Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered ...

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    1-24 of 54 1 2 3 »
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    1. (54 articles) Vivek J. Srinivasan
    2. (26 articles) UC Davis
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