Defining metrics of visual acuity from theoretical models of observers.

Many experimental studies show that metrics of visual image quality can predict changes in visual acuity due to optical aberrations. Here we use statistical decision theory and Fourier optics formalism to demonstrate that two metrics known in the field of vision sciences are approximations of two different theoretical models of linear observers. The theory defines metrics of visual acuity to potentially predict changes in visual acuity due to optical aberrations, without needing a posteriori scale or offset. We illustrate our approach with experiments, using combinations of defocus and spherical aberration, and pure coma.

Absolute prediction of relative changes in contrast sensitivity with aberrations using a single metric of retinal image quality.

Metrics of retinal image quality predict optimal refractive corrections and correlate with visual performance. To date, they do not predict absolutely the relative change in visual performance when aberrations change and therefore need to be a-posteriori rescaled to match relative measurements. Here we demonstrate that a recently proposed metric can be used to predict, in an absolute manner, changes in contrast sensitivity measurements with Sloan letters when aberrations change. Typical aberrations of young and healthy eyes (for a 6 mm pupil diameter) were numerically introduced, and we measured the resulting loss in contrast sensitivity of subjects looking through a 2 mm diameter pupil. Our results suggest that the metric can be used to corroborate measurements of visual performance in clinical practice, thereby potentially improving patient follow-ups.

Predicting the effects of defocus blur on contrast sensitivity with a model-based metric of retinal image quality.

We measure the effect of defocus blur on contrast sensitivity with Sloan letters in the 0.75-2.00 arc min range of letter gaps. We compare our results with the prediction of the Dalimier and Dainty model [J. Opt. Soc. Am. A25, 2078 (2008)JOAOD60740-323210.1364/JOSAA.25.002078] and propose a new metric of retinal image quality that we define as the model limit for very small letters. The contrast sensitivity is measured for computationally blurred Sloan letters (0, 0.25, and 0.50 diopters for a 3 mm pupil) of different sizes (20/40 to 20/15 visual acuity), and subjects look through a small (2 mm) diaphragm to limit the impact of their own aberration on measurements. Measurements and model predictions, which are normalized by the blur-free condition, weakly depend on letter size and are in good agreement with our metric of retinal image quality. Our metric relates two approaches of modeling visual performance: complete modeling of the optotype classification task and calculation of retinal image quality with a descriptive metric.

The random walk of accommodation fluctuations.

The focusing distance of the eye fluctuates during accommodation. However, the visual role of these accommodation fluctuations is not yet fully understood. The fluctuation complexity is one of the obstacles to this long standing challenge in visual science. In this work we seek to develop a statistical approach that i) accurately describes experimental measurements and ii) directly generates randomized and realistic simulations of accommodation fluctuations for use in future experiments. To do so we use the random walk approach, which is usually appropriate to describe the dynamics of systems that combine both randomness and memory.

Analysis of macular curvature in normal eyes using swept-source optical coherence tomography.

PURPOSE: To evaluate macular shape in normal eyes using swept-source optical coherence tomography (SS-OCT). STUDY DESIGN: Retrospective cross-sectional study. METHODS: We retrospectively evaluated 77 normal eyes of 48 subjects. Curvature of retinal pitment epithelium (RPE) and choroid/scleral interface (CSI) was measured in vertical and horizontal SS-OCT 16-mm scanned images. After correcting the optical distortion of OCT images, curvatures of superior, central, and inferior sectors in the vertical scan, and temporal, central, and nasal sectors in the horizontal scan (each 4-mm length) were compared. Factors associated with overall RPE and CSI curvatures were investigated. RESULTS: RPE and CSI curvatures of superior, central, and inferior sectors in the vertical scan were 16.6±3.1, 13.8±2.1, 17.7±3.2 and 17.8±3.0, 13.8±3.3, 18.4±3.3 (×10-5 µm-1), respectively. Central curvature was significantly flatter than superior and inferior curvatures in both RPE and CSI (all P<0.001). The RPE and CSI curvatures of temporal, central, and nasal sectors in the horizontal scan were 17.2±2.3, 15.2±2.5, 18.8±2.7 and 18.3±2.7, 16.7±2.9,14.4±2.9 (×10-5 µm-1), respectively. While central curvature was significantly flatter than nasal and temporal curvatures in RPE (P<0.001 and P=0.025), nasal curvature was significantly flatter than central and temporal curvatures (P=0.027 and P<0.001) in CSI. Overall CSI curvature was significantly associated with axial length (AL) (P<0.001), whereas overall RPE curvature was significantly associated with overall CSI curvature (P<0.001), choroidal thickness (P<0.001), and AL (P=0.038) CONCLUSIONS: This study revealed that RPE curvature is associated with CSI curvature, choroidal thickness, and AL, suggesting that choroidal and scleral structures affect macular RPE curvature.

Highly Tunable Hollow Gold Nanospheres: Gaining Size Control and Uniform Galvanic Exchange of Sacrificial Cobalt Boride Scaffolds.

In principle, the diameter and surface plasmon resonance (SPR) frequency of hollow metal nanostructures can be independently adjusted, allowing the formation of targeted photoactivated structures of specific size and optical functionality. Although tunable SPRs have been reported for various systems, the shift in SPR is usually concomitant with a change in particle size. As such, more advanced tunability, including constant diameter with varying SPR or constant SPR with varying diameter, has not been properly achieved experimentally. Herein, we demonstrate this advanced tunability with hollow gold nanospheres (HGNs). HGNs were synthesized through galvanic exchange using cobalt-based nanoparticles (NPs) as sacrificial scaffolds. Co2B NP scaffolds were prepared by sodium borohydride nucleation of aqueous cobalt chloride and characterized using UV-vis, dynamic light scattering, X-ray absorption spectroscopy, and X-ray photoelectron spectroscopy. Careful control over the size of the Co2B scaffold and its galvanic conversion is essential to realize fine control of the resultant HGN diameter and shell thickness. In pursuit of size control, we introduce B(OH)4- (the final product of NaBH4 hydrolysis) as a growth agent to obtain hydrodynamic diameters ranging from ∼17-85 nm with relative standard deviation <3%. The highly monodisperse Co2B NPs were then used as scaffolds for the formation of HGNs. In controlling HGN shell thickness and uniformity, environmental oxygen was shown to affect both the structural and optical properties of the resultant gold shells. With careful control of these key factors, we demonstrate an HGN synthesis that enables independent variation of diameter and shell thickness, and thereby SPR, with unprecedented uniformity. The new synthesis method creates a truly tunable plasmonic nanostructure platform highly desirable for a wide range of applications, including sensing, catalysis, and photothermal therapy.

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 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.

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 that achieves a reconstruction of cortical microvasculature from OCM angiography data sets with accuracy approaching that attained by trained operators. The automated techniques described here will facilitate more widespread study of vascular network topology in health and disease.

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 (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.

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 induced by vessel dilations were inferred. RESULTS: A topologically-representative 3D vectorized graph of the inner retinal vasculature, derived from OCT angiography data, is presented. The laminar and compartmental connectivity of the vasculature are characterized. In contrast to sparse connectivity between the superficial vitreal vasculature and capillary plexuses of the inner retina, connectivity between the two capillary plexus layers is dense. Simulated dilation of single arterioles is shown to produce both localized and lamina-specific changes in blood flow, while dilation of capillaries in a given retinal vascular layer is shown to lead to increased total flow in that layer. CONCLUSIONS: Our graphing and modeling data suggest that vascular architecture enables both local and lamina-specific control of blood flow in the inner retina. The imaging, graph analysis, and modeling approach presented here will help provide a detailed characterization of vascular changes in a variety of retinal diseases, both in experimental preclinical models and human subjects.

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 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.

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 verified by ex vivo blood measurements at various pO2 and hematocrit levels. Imaging results from the rodent brain and retina are presented. Confounds including noise and scattering, as well as potential clinical applications, are discussed.

Imaging system to assess objectively the optical density of the macular pigment in vivo.

This paper presents an optical system called MacPI, which implements a two-color reflectance technique in combination with various hardware and software tools to assess objectively the macular pigment (MP) optical density in vivo. The system consists of a bespoke optical design, a control architecture, driver electronics, a collection of image-processing techniques, and a graphical user interface. The deficiencies of the technique employed and the solutions implemented in the MacPI system to confront those inherent frailties are presented. An overview of the effective interpretation of the acquired data and the techniques employed by MacPI in the acquisition of that data is discussed. The result of a comparison trial with an alternative device is also presented. We suggest that appropriate design of the hardware and an efficient interpretation of the acquired data should produce a system capable of consistent, accurate, and rapid measurements, while retaining the distinction of ease of use, portability, comfort for the subject, and a design that is economic to produce. Its versatility should allow both for a clinical screening application and for further investigation and establishment of the physiological role of the MP in a laboratory-based environment.

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 ex vivo. Architectonic features show the expected laminar characteristics; moreover, changes in contrast after the application of acetic acid suggest that entire neuronal cell bodies are responsible for the "negative contrast" present in the images. Clearing and imaging techniques that preserve tissue architectural integrity have the potential to enable non-invasive studies of the brain during development, disease, and remodeling, even in samples where exogenous labeling is impractical.

Illumination correction of retinal images using Laplace interpolation.

Retinal images are frequently corrupted by unwanted variations in intensity that occur due to general imperfections in the image acquisition process. This inhomogeneous illumination across the retina can limit the useful information accessible within the acquired image. Specifically, this can lead to serious difficulties when performing image processing tasks requiring quantitative analysis of features present on the retina. Given that the spatial frequency content of the shading profile often overlaps with that of retinal features, retrospectively correcting for inhomogeneous illumination while maintaining the radiometric fidelity of the real data can be challenging. This paper describes a simple method for obtaining an estimate of the illumination profile in retinal images, with the particular goal of minimizing its influence upon features of interest. This is achieved by making use of Laplace interpolation and a multiplicative image formation model.