Persistence of Cloquet's Canal in Normal Healthy Eyes

American Journal of Ophthalmology. Nov, 2006  |  Pubmed ID: 17056372

Optic nerve head (ONH) structural imaging with state-of-the-art, high-speed, ultra-high-resolution optical coherence tomography (hsUHR-OCT).

High-definition and 3-dimensional Imaging of Macular Pathologies with High-speed Ultrahigh-resolution Optical Coherence Tomography

Ophthalmology. Nov, 2006  |  Pubmed ID: 17074565

To assess high-speed ultrahigh-resolution optical coherence tomography (OCT) image resolution, acquisition speed, image quality, and retinal coverage for the visualization of macular pathologies.

Noninvasive Volumetric Imaging and Morphometry of the Rodent Retina with High-speed, Ultrahigh-resolution Optical Coherence Tomography

Investigative Ophthalmology & Visual Science. Dec, 2006  |  Pubmed ID: 17122144

To demonstrate high-speed, ultrahigh-resolution optical coherence tomography (OCT) for noninvasive, in vivo, three-dimensional imaging of the retina in rat and mouse models.

Extracellular Carbonic Anhydrase Mediates Hemorrhagic Retinal and Cerebral Vascular Permeability Through Prekallikrein Activation

Nature Medicine. Feb, 2007  |  Pubmed ID: 17259996

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.

Peripapillary Schisis in Glaucoma Patients with Narrow Angles and Increased Intraocular Pressure

American Journal of Ophthalmology. Apr, 2007  |  Pubmed ID: 17386284

To describe two cases of peripapillary retinal schisis in patients with glaucoma without evidence of optic nerve pits, pseudopits, or X-linked retinoschisis.

Peripapillary Nerve Fiber Layer Thickness Profile Determined with High Speed, Ultrahigh Resolution Optical Coherence Tomography High-density Scanning

Investigative Ophthalmology & Visual Science. Jul, 2007  |  Pubmed ID: 17591885

To determine the retinal nerve fiber layer (RNFL) thickness profile in the peripapillary region of healthy eyes.

Analysis of Posterior Retinal Layers in Spectral Optical Coherence Tomography Images of the Normal Retina and Retinal Pathologies

Journal of Biomedical Optics. Jul-Aug, 2007  |  Pubmed ID: 17867796

We present a computationally efficient, semiautomated method for analysis of posterior retinal layers in three-dimensional (3-D) images obtained by spectral optical coherence tomography (SOCT). The method consists of two steps: segmentation of posterior retinal layers and analysis of their thickness and distance from an outer retinal contour (ORC), which is introduced to approximate the normal position of external interface of the healthy retinal pigment epithelium (RPE). The algorithm is shown to effectively segment posterior retina by classifying every pixel in the SOCT tomogram using the similarity of its surroundings to a reference set of model pixels from user-selected area(s). Operator intervention is required to assess the quality of segmentation. Thickness and distance maps from the segmented layers and their analysis are presented for healthy and pathological retinas.

Spectral Oximetry Assessed with High-speed Ultra-high-resolution Optical Coherence Tomography

Journal of Biomedical Optics. Jul-Aug, 2007  |  Pubmed ID: 17867801

We use Fourier domain optical coherence tomography (OCT) data to assess retinal blood oxygen saturation. Three-dimensional disk-centered retinal tissue volumes were assessed in 17 normal healthy subjects. After removing DC and low-frequency a-scan components, an OCT fundus image was created by integrating total reflectance into a single reflectance value. Thirty fringe patterns were sampled; 10 each from the edge of an artery, adjacent tissue, and the edge of a vein, respectively. A-scans were recalculated, zeroing the DC term in the power spectrum, and used for analysis. Optical density ratios (ODRs) were calculated as ODR(Art)=ln(Tissue(855)Art(855))ln(Tissue(805)Art(805)) and ODR(Vein)=ln(Tissue(855)Vein(855))ln(Tissue(805)Vein(805)) with Tissue, Art, and Vein representing total a-scan reflectance at the 805- or 855-nm centered bandwidth. Arterial and venous ODRs were compared by the Wilcoxon signed rank test. Arterial ODRs were significantly greater than venous ODRs (1.007+/-2.611 and -1.434+/-4.310, respectively; p=0.0217) (mean+/-standard deviation). A difference between arterial and venous blood saturation was detected. This suggests that retinal oximetry may possibly be added as a metabolic measurement in structural imaging devices.

High-speed, Ultrahigh Resolution Optical Coherence Tomography of the Retina in Hunter Syndrome

Ophthalmic Surgery, Lasers & Imaging : the Official Journal of the International Society for Imaging in the Eye. Sep-Oct, 2007  |  Pubmed ID: 17955852

A 42-year-old man with Hunter syndrome developed bilateral visual field loss. Visual field testing demon-strated 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.

Photoreceptor Disruption Secondary to Posterior Vitreous Detachment As Visualized Using High-speed Ultrahigh-resolution Optical Coherence Tomography

Archives of Ophthalmology. Nov, 2007  |  Pubmed ID: 17998527

Characterization of Outer Retinal Morphology with High-speed, Ultrahigh-resolution Optical Coherence Tomography

Investigative Ophthalmology & Visual Science. Apr, 2008  |  Pubmed ID: 18385077

To visualize, quantitatively assess, and interpret outer retinal morphology by using high-speed, ultrahigh-resolution (UHR) OCT.

Optical Coherence Tomography Scan Circle Location and Mean Retinal Nerve Fiber Layer Measurement Variability

Investigative Ophthalmology & Visual Science. Jun, 2008  |  Pubmed ID: 18515577

To investigate the effect on optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness measurements of varying the standard 3.4-mm-diameter circle location.

Ultrahigh-speed Optical Coherence Tomography for Three-dimensional and En Face Imaging of the Retina and Optic Nerve Head

Investigative Ophthalmology & Visual Science. Nov, 2008  |  Pubmed ID: 18658089

To demonstrate ultrahigh-speed optical coherence tomography (OCT) imaging of the retina and optic nerve head at 249,000 axial scans per second and a wavelength of 1060 nm. To investigate methods for visualization of the retina, choroid, and optic nerve using high-density sampling enabled by improved imaging speed.

Ultrahigh Speed Spectral / Fourier Domain OCT Ophthalmic Imaging at 70,000 to 312,500 Axial Scans Per Second

Optics Express. Sep, 2008  |  Pubmed ID: 18795054

We demonstrate ultrahigh speed spectral / Fourier domain optical coherence tomography (OCT) using an ultrahigh speed CMOS line scan camera at rates of 70,000 - 312,500 axial scans per second. Several design configurations are characterized to illustrate trade-offs between acquisition speed, resolution, imaging range, sensitivity and sensitivity roll-off performance. Ultrahigh resolution OCT with 2.5 - 3.0 micron axial image resolution is demonstrated at approximately 100,000 axial scans per second. A high resolution spectrometer design improves sensitivity roll-off and imaging range performance, trading off imaging speed to 70,000 axial scans per second. Ultrahigh speed imaging at >300,000 axial scans per second with standard image resolution is also demonstrated. Ophthalmic OCT imaging of the normal human retina is investigated. The high acquisition speeds enable dense raster scanning to acquire densely sampled volumetric three dimensional OCT (3D-OCT) data sets of the macula and optic disc with minimal motion artifacts. Imaging with approximately 8 - 9 micron axial resolution at 250,000 axial scans per second, a 512 x 512 x 400 voxel volumetric 3D-OCT data set can be acquired in only approximately 1.3 seconds. Orthogonal registration scans are used to register OCT raster scans and remove residual axial eye motion, resulting in 3D-OCT data sets which preserve retinal topography. Rapid repetitive imaging over small volumes can visualize small retinal features without motion induced distortions and enables volume registration to remove eye motion. Cone photoreceptors in some regions of the retina can be visualized without adaptive optics or active eye tracking. Rapid repetitive imaging of 3D volumes also provides dynamic volumetric information (4D-OCT) which is shown to enhance visualization of retinal capillaries and should enable functional imaging. Improvements in the speed and performance of 3D-OCT volumetric imaging promise to enable earlier diagnosis and improved monitoring of disease progression and response to therapy in ophthalmology, as well as have a wide range of research and clinical applications in other areas.

Real Time En Face Fourier-domain Optical Coherence Tomography with Direct Hardware Frequency Demodulation

Optics Letters. Nov, 2008  |  Pubmed ID: 18978919

We demonstrate en face swept source optical coherence tomography (ss-OCT) without requiring a Fourier transformation step. The electronic optical coherence tomography (OCT) interference signal from a k-space linear Fourier domain mode-locked laser is mixed with an adjustable local oscillator, yielding the analytic reflectance signal from one image depth for each frequency sweep of the laser. Furthermore, a method for arbitrarily shaping the spectral intensity profile of the laser is presented, without requiring the step of numerical apodization. In combination, these two techniques enable sampling of the in-phase and quadrature signal with a slow analog-to-digital converter and allow for real-time display of en face projections even for highest axial scan rates. Image data generated with this technique is compared to en face images extracted from a three-dimensional OCT data set. This technique can allow for real-time visualization of arbitrarily oriented en face planes for the purpose of alignment, registration, or operator-guided survey scans while simultaneously maintaining the full capability of high-speed volumetric ss-OCT functionality.

High-Speed Ultrahigh-Resolution Optical Coherence Tomography Findings in Chronic Solar Retinopathy

Retinal Cases & Brief Reports. 2008  |  Pubmed ID: 19756263

PURPOSE: To describe ocular findings for a 34-year-old man with chronic solar retinopathy using high-speed ultrahigh-resolution (UHR) optical coherence tomography (OCT). METHODS: Fundus photography, fluorescein angiography, and Stratus OCT (Carl Zeiss Meditec, Inc., Dublin, CA) were performed. A high-speed UHR OCT prototype developed in our ophthalmology clinic was used to obtain detailed images of the retina. PATIENTS: Two eyes of one patient with chronic solar retinopathy were studied. RESULTS: Both Stratus OCT and high-speed UHR OCT demonstrated foveal thinning bilaterally. In addition, high-speed UHR OCT showed distinct hyporeflective disruptions in the photoreceptor inner segment/outer segment junction and photoreceptor outer segments bilaterally. En face OCT images from three-dimensional OCT data sets revealed hyporeflective regions of photoreceptor atrophy in the outer retina. CONCLUSIONS: High-speed UHR OCT showed more detail than standard OCT, and findings were consistent with histopathologic and ultrastructural features that have been reported previously. Solar retinopathy should be studied further with high-speed UHR OCT to determine the short- and long-term effects of solar radiation damage.

Depth-resolved Microscopy of Cortical Hemodynamics with Optical Coherence Tomography

Optics Letters. Oct, 2009  |  Pubmed ID: 19838234

We describe depth-resolved microscopy of cortical hemodynamics with high-speed spectral/Fourier domain optical coherence tomography (OCT). Stimulus-evoked changes in blood vessel diameter, flow, and total hemoglobin were measured in the rat somatosensory cortex. The results show OCT measurements of hemodynamic changes during functional activation and represent an important step toward understanding functional hyperemia at the microscopic level.

Optical Monitoring of Oxygen Tension in Cortical Microvessels with Confocal Microscopy

Optics Express. Dec, 2009  |  Pubmed ID: 20052157

Evaluating cerebral oxygenation is of critical importance for the understanding of brain function and several neuropathologies. Although several techniques exist for measuring cerebral oxygenation in vivo, the most widely accepted techniques offer limited spatial resolution. We have developed a confocal imaging system for minimally invasive measurement of oxygen tension (pO(2)) in cerebral microvessels with high spatial and temporal resolution. The system relies on the phosphorescence quenching method using exogenous porphyrin-based dendritic oxygen probes. Here we present high-resolution phosphorescence images of cortical microvasculature and temporal pO(2) profiles from multiple locations in response to varied fraction of inspired oxygen and functional activation.

Three-dimensional Ultrahigh Resolution Optical Coherence Tomography Imaging of Age-related Macular Degeneration

Optics Express. Mar, 2009  |  Pubmed ID: 19259245

Ultrahigh resolution optical coherence tomography (OCT) enhances the ability to visualize different intra retinal layers. In age-related macular degeneration (AMD), pathological changes in individual retinal layers, including photoreceptor inner and outer segments and retinal pigment epithelium, can be detected. OCT using spectral / Fourier domain detection enables high speed, volumetric imaging of the macula, which provides comprehensive three-dimensional tomographic and morphologic information. We present a case series of AMD patients, from mild drusen to more advanced geographic atrophy and exudative AMD. Patients were imaged with a research prototype, ultrahigh resolution spectral / Fourier domain OCT instrument with 3.5 microm axial image resolution operating at 25,000 axial scans per second. These cases provide representative volumetric datasets of well-documented AMD pathologies which could be used for the development of visualization and imaging processing methods and algorithms.

High-speed Ultrahigh Resolution Optical Coherence Tomography Before and After Ranibizumab for Age-related Macular Degeneration

Ophthalmology. May, 2009  |  Pubmed ID: 19410953

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.

Quantitative Cerebral Blood Flow with Optical Coherence Tomography

Optics Express. Feb, 2010  |  Pubmed ID: 20174075

Absolute measurements of cerebral blood flow (CBF) are an important endpoint in studies of cerebral pathophysiology. Currently no accepted method exists for in vivo longitudinal monitoring of CBF with high resolution in rats and mice. Using three-dimensional Doppler Optical Coherence Tomography and cranial window preparations, we present methods and algorithms for regional CBF measurements in the rat cortex. Towards this end, we develop and validate a quantitative statistical model to describe the effect of static tissue on velocity sensitivity. This model is used to design scanning protocols and algorithms for sensitive 3D flow measurements and angiography of the cortex. We also introduce a method of absolute flow calculation that does not require explicit knowledge of vessel angles. We show that OCT estimates of absolute CBF values in rats agree with prior measures by autoradiography, suggesting that Doppler OCT can perform absolute flow measurements in animal models.

Rapid Volumetric Angiography of Cortical Microvasculature with Optical Coherence Tomography

Optics Letters. Jan, 2010  |  Pubmed ID: 20664667

We describe methods and algorithms for rapid volumetric imaging of cortical vasculature with optical coherence tomography (OCT). By optimizing system design, scanning protocols, and algorithms for visualization of capillary flow, comprehensive imaging of the surface pial vasculature and capillary bed is performed in approximately 12 s. By imaging during hypercapnia and comparing with simultaneous CCD imaging, the sources of contrast of OCT angiography are investigated.

Two-photon High-resolution Measurement of Partial Pressure of Oxygen in Cerebral Vasculature and Tissue

Nature Methods. Sep, 2010  |  Pubmed ID: 20693997

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.

Comparison of Spectral/Fourier Domain Optical Coherence Tomography Instruments for Assessment of Normal Macular Thickness

Retina (Philadelphia, Pa.). Feb, 2010  |  Pubmed ID: 19952997

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).

Two-photon Microscopy of Cortical NADH Fluorescence Intensity Changes: Correcting Contamination from the Hemodynamic Response

Journal of Biomedical Optics. Oct, 2011  |  Pubmed ID: 22029350

Quantification of nicotinamide adenine dinucleotide (NADH) changes during functional brain activation and pathological conditions provides critical insight into brain metabolism. Of the different imaging modalities, two-photon laser scanning microscopy (TPLSM) is becoming an important tool for cellular-resolution measurements of NADH changes associated with cellular metabolic changes. However, NADH fluorescence emission is strongly absorbed by hemoglobin. As a result, in vivo measurements are significantly affected by the hemodynamics associated with physiological and pathophysiological manipulations. We model NADH fluorescence excitation and emission in TPLSM imaging based on precise maps of cerebral microvasculature. The effects of hemoglobin optical absorption and optical scattering from red blood cells, changes in blood volume and hemoglobin oxygen saturation, vessel size, and location with respect to imaging location are explored. A simple technique for correcting the measured NADH fluorescence intensity changes is provided, with the utilization of a parallel measurement of a physiologically inert fluorophore. The model is applied to TPLSM measurements of NADH fluorescence intensity changes in rat somatosensory cortex during mild hypoxia and hyperoxia. The general approach of the correction algorithm can be extended to other TPLSM measurements, where changes in the optical properties of the tissue confound physiological measurements, such as the detection of calcium dynamics.

Microvascular Oxygen Tension and Flow Measurements in Rodent Cerebral Cortex During Baseline Conditions and Functional Activation

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. Apr, 2011  |  Pubmed ID: 21179069

Measuring cerebral oxygen delivery and metabolism microscopically is important for interpreting macroscopic functional magnetic resonance imaging (fMRI) data and identifying pathological changes associated with stroke, Alzheimer's disease, and brain injury. Here, we present simultaneous, microscopic measurements of cerebral blood flow (CBF) and oxygen partial pressure (pO(2)) in cortical microvessels of anesthetized rats under baseline conditions and during somatosensory stimulation. Using a custom-built imaging system, we measured CBF with Fourier-domain optical coherence tomography (OCT), and vascular pO(2) with confocal phosphorescence lifetime microscopy. Cerebral blood flow and pO(2) measurements displayed heterogeneity over distances irresolvable with fMRI and positron emission tomography. Baseline measurements indicate O(2) extraction from pial arterioles and homogeneity of ascending venule pO(2) despite large variation in microvessel flows. Oxygen extraction is linearly related to flow in ascending venules, suggesting that flow in ascending venules closely matches oxygen demand of the drained territory. Oxygen partial pressure and relative CBF transients during somatosensory stimulation further indicate arteriolar O(2) extraction and suggest that arterioles contribute to the fMRI blood oxygen level dependent response. Understanding O(2) supply on a microscopic level will yield better insight into brain function and the underlying mechanisms of various neuropathologies.

Intact Retinal Tissue and Retinal Pigment Epithelium Identified Within a Coloboma Via High-Speed, Ultrahigh Resolution Optical Coherence Tomography

Retinal Cases & Brief Reports. 2011  |  Pubmed ID: 21218127

PURPOSE: To report on a posterior segment coloboma manifesting unusual morphology as determined by high-speed, ultrahigh resolution optical coherence tomography imaging (hsUHR-OCT). METHODS: A 47-year-old patient with bilateral colobomas was evaluated via fundus examination and hsUHR-OCT. RESULTS: Imaging with hsUHR-OCT showed intact retinal pigment epithelium (RPE) within the posterior segment coloboma. Most of the retinal layers appeared to continue into the coloboma, although they exhibited slight attenuation. The external limiting membrane (ELM) was clearly visible continuing within the coloboma, suggesting that Muller cells and the inner segments of the photoreceptors were still present in this area. The junction between the inner and outer segments of the photoreceptors ended at the margin of the coloboma, which may be due to either photoreceptor disruption or a change in the orientation of the outer segments. CONCLUSION: hsUHR-OCT demonstrated the presence of Muller cells and photoreceptor inner segments within a posterior segment coloboma. The retinal pigment epithelium (RPE) was intact within the coloboma, representing an unusual morphology.

Optical Coherence Tomography for the Quantitative Study of Cerebrovascular Physiology

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. Jun, 2011  |  Pubmed ID: 21364599

Doppler optical coherence tomography (DOCT) and OCT angiography are novel methods to investigate cerebrovascular physiology. In the rodent cortex, DOCT flow displays features characteristic of cerebral blood flow, including conservation along nonbranching vascular segments and at branch points. Moreover, DOCT flow values correlate with hydrogen clearance flow values when both are measured simultaneously. These data validate DOCT as a noninvasive quantitative method to measure tissue perfusion over a physiologic range.

Due to Intravascular Multiple Sequential Scattering, Diffuse Correlation Spectroscopy of Tissue Primarily Measures Relative Red Blood Cell Motion Within Vessels

Biomedical Optics Express. Jul, 2011  |  Pubmed ID: 21750779

We suggest that Diffuse Correlation Spectroscopy (DCS) measurements of tissue blood flow primarily probe relative red blood cell (RBC) motion, due to the occurrence of multiple sequential scattering events within blood vessels. The magnitude of RBC shear-induced diffusion is known to correlate with flow velocity, explaining previous reports of linear scaling of the DCS "blood flow index" with tissue perfusion despite the observed diffusion-like auto-correlation decay. Further, by modeling RBC mean square displacement using a formulation that captures the transition from ballistic to diffusive motion, we improve the fit to experimental data and recover effective diffusion coefficients and velocity de-correlation time scales in the range expected from previous blood rheology studies.

"Overshoot" of O₂ is Required to Maintain Baseline Tissue Oxygenation at Locations Distal to Blood Vessels

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Sep, 2011  |  Pubmed ID: 21940458

In vivo imaging 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 pO₂ depended on the baseline pO₂ level. In particular, during sustained stimulation, the steady-state pO₂ at low-baseline locations remained at the baseline, despite large pO₂ increases elsewhere. In contrast to the steady state, where pO₂ never 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.

Cortical Spreading Depression Impairs Oxygen Delivery and Metabolism in Mice

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. Feb, 2012  |  Pubmed ID: 22008729

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.

Frontiers in Optical Imaging of Cerebral Blood Flow and Metabolism

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. Jan, 2012  |  Pubmed ID: 22252238

In vivo optical imaging of cerebral blood flow (CBF) and metabolism did not exist 50 years ago. While point optical fluorescence and absorption measurements of cellular metabolism and hemoglobin concentrations had already been introduced by then, point blood flow measurements appeared only 40 years ago. The advent of digital cameras has significantly advanced two-dimensional optical imaging of neuronal, metabolic, vascular, and hemodynamic signals. More recently, advanced laser sources have enabled a variety of novel three-dimensional high-spatial-resolution imaging approaches. Combined, as we discuss here, these methods are permitting a multifaceted investigation of the local regulation of CBF and metabolism with unprecedented spatial and temporal resolution. Through multimodal combination of these optical techniques with genetic methods of encoding optical reporter and actuator proteins, the future is bright for solving the mysteries of neurometabolic and neurovascular coupling and translating them to clinical utility.Journal of Cerebral Blood Flow & Metabolism advance online publication, 18 January 2012; doi:10.1038/jcbfm.2011.195.

Optical Coherence Microscopy for Deep Tissue Imaging of the Cerebral Cortex with Intrinsic Contrast

Optics Express. Jan, 2012  |  Pubmed ID: 22330462

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.