Eric Logean

Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina

The retina and optic nerve are both optically accessible parts of the central nervous system. They represent, therefore, highly valuable tissues for studies of the intrinsic physiological mechanism postulated more than 100 years ago by Roy and Sherrington, by which neural activity is coupled to blood flow and metabolism. This article describes a series of animal and human studies that explored the changes in hemodynamics and oxygenation in the retina and optic nerve in response to increased neural activity, as well as the mechanisms underlying these changes. It starts with a brief review of techniques used to assess changes in neural activity, hemodynamics, metabolism and tissue concentration of various potential mediators and modulators of the coupling. We then review: (a) the characteristics of the flicker-induced hemodynamical response in different regions of the eye, starting with the optic nerve, the region predominantly studied; (b) the effect of varying the stimulus parameters, such as modulation depth, frequency, luminance, color ratio, area of stimulation, site of measurement and others, on this response; (c) data on activity-induced intrinsic reflectance and functional magnetic resonance imaging signals from the optic nerve and retina. The data undeniably demonstrate that visual stimulation is a powerful modulator of retinal and optic nerve blood flow. Exploring the relationship between vasoactivity and metabolic changes on one side and corresponding neural activity changes on the other confirms the existence of a neurovascular/neurometabolic coupling in the neural tissue of the eye fundus and reveals that the mechanism underlying this coupling is complex and multi-factorial. The importance of fully exploiting the potential of the activity-induced vascular changes in the assessment of the pathophysiology of ocular diseases motivated studies aimed at identifying potential mediators and modulators of the functional hyperemia, as well as conditions susceptible to alter this physiological response. Altered hemodynamical responses to flicker were indeed observed during a number of physiological and pharmacological interventions and in a number of clinical conditions, such as essential systemic hypertension, diabetes, ocular hypertension and early open-angle glaucoma. The article concludes with a discussion of key questions that remain to be elucidated to increase our understanding of the physiology of ocular functional hyperemia and establish the importance of assessing the neurovascular coupling in the diagnosis and management of optic nerve and retinal diseases.

Temporal dynamics and magnitude of the blood flow response at the optic disk in normal subjects during functional retinal flicker-stimulation

Near-infrared laser Doppler flowmetry was applied in 15 normal volunteers to record the time course and magnitude of changes in the velocity (Vel), volume (Vol) and flow (F) of blood and tissue reflectance (R) at the optic disk in response to 40 and 50 s of increased retinal neural activity. This activity was evoked by diffuse luminance flicker of the retinal posterior pole. After 20 s of flicker, the group averages of Vel, Vol, and F were significantly higher than at baseline (pre-flicker) by 12, 24 and 38%. Time constants of the increases in Vel, Vol, and F were 3.4, 12.7 and 9.1 s, respectively. The group average change in R of 1% was not significant. However, in one subject, 15 recordings from the same site of the optic disk showed a significant increase in R of 8%, with a time course similar to that of Vol. Our findings show that, in the human optic nerve, a white matter tissue, the temporal dynamics and magnitude of the response of blood flow to an increase in retinal neural activity are similar to those reported for brain gray matter. Furthermore, although the R-response could be due, in part, to changes in blood volume, other factors, such as activity-evoked tissue scattering changes, may also affect this response.

Measured double-pass intensity point-spread function after adaptive optics correction of ocular aberrations

The double-pass intensity point-spread function was recorded in four subjects using a monochromatic source emitting at 543 nm, through a 6.7-mm diameter pupil i) at the fovea after adaptive optics correction of the ocular aberrations, ii) at the fovea without adaptive optics correction, and iii) at 2 degrees of eccentricity with adaptive optics correction. The half-width at half-maximum of the double-pass point-spread function was narrower after correction of the ocular aberrations. At 2 degrees of eccentricity this width was larger than at the fovea. The minimum widths were about 1.1 arcmin in dark pigmented eyes and 1.6 arcmin in light pigmented eyes. These values are 6 to 9 times larger than the width expected from diffraction alone.

Optical Doppler velocimetry at various retinal vessel depths by variation of the source coherence length.

We report on what we believe is a novel approach to measuring the velocity of red blood cells (RBCs) at different depths of retinal vessels by use of low-coherence sources. The technique, variable coherence optical Doppler velocimetry (VCODV), performs Doppler shift measurements through autodyne mixing between the light scattered by the RBCs and by the vessel front wall (reference). Only the light from RBCs moving at a depth less than half the coherence length (CL) mixes efficiently with the reference. Measurements of the Doppler shifts from RBCs with sources of four different CLs in a 152-microm vein of a volunteer confirmed the feasibility of VCODV. This approach has the potential to monitor in vivo retinal RBC velocity gradient at the vessel wall and the velocity profile within the blood vessel in the condition of symmetric blood flow profiles.

Experimental demonstration of ray-optical refraction with confocal lenslet arrays

We observe imaging through windows comprising pairs of confocal lenslet arrays that have different focal lengths but that are otherwise identical. Image space is stretched in the longitudinal direction only. Such windows are examples of METATOYs, optical components that can change light-ray direction in ways that appear wave-optically forbidden.

Measurement of eye length and eye shape by optical low coherence reflectometry

Background: The precise and rapid measurement ofeye length and eye shape isessential for investigating eye growth regulation andmyopia. For this purpose, we developedan optical low coherence reflectometer (OLCR) andpresent preliminary measurements.Methods: The OLCR includes a super luminescentdiode (wavelength: 845 nm,coherence length: ∼30 μm) and rotatingglass cube to produce longitudinal scansat a velocity of 0.42 m/s and a repetition rateof ∼13 scans/s. Heterodyne detection oflight reflected from the anterior cornea andthe posterior retina permits to measure axial eyelength and eye shape (off-axis eye length).Each measurement consists of five consecutivescans. Reproducibility and precision weredetermined in one volunteer by measuring axialeye length five consecutive times, each timerepositioning the eye. Eye shapes weredetermined in right eyes of four volunteers bymeasuring eye length every 3.3° from10° nasally to 10° temporally.Results: Axial eye length measured repeatedlyin one volunteer did not differ between orwithin the measurements (one-factor ANOVA). Theaverage standard deviation was11 μm. Eye shapes (a) varied substantiallyamong subjects and (b) differed considerablyfrom the corresponding shapes of sphericalmodel eyes with identical axial eye lengths.Conclusion: The newly developed OLCRpermits the precise and rapid measurement ofeye length and eye shape. Such measurements,especially in children, may provide importantinformation about mechanisms of eye growthregulation and the development of myopia.

High numerical aperture silicon collimating lens for mid-infrared quantum cascade lasers manufactured using wafer-level techniques

We present an aspheric collimating lens for mid-infrared (4-14 μm) quantum cascade lasers. The lenses were etched into silicon by an inductively coupled plasma reactive ion etching system on wafer level. The high refractive index of silicon reduces the height of the lens profile resulting in a simple element working at high numerical aperture (up to 0.82). Wafer level processes enable the fabrication of about 5000 lenses in parallel. Such cost-effective collimating lens is a step towards the adoption of quantum cascade lasers for all its potential applications.

Hyperemic responses of the optic nerve head blood flow to chromatic equiluminant flicker are reduced by ocular hypertension and early glaucoma

Abstract. We evaluated in ocular hypertension (OHT) and early glaucoma (EOAG) patients the optic nerve head (ONH) blood flow response (RFonh) to chromatic equiluminant flicker. This stimulus generates neural activity dominated by the parvo-cellular system. Eleven EOAG, 20 OHT patients, and 8 age-matched control subjects were examined. The blood flow (Fonh) at the neuroretinal rim was continuously monitored by laser Doppler flowmetry before, during, and after a 60-s exposure to a 4 Hz, red-green equiluminant flicker stimulus (30 deg field). RFonh was expressed as percentage Fonh-change during the last 20 s of flicker relative to baseline Fonh. Responses were collected at a number of temporal sites. The highest RFonh value was used for subsequent analysis. As compared to controls, both OHT and EOAG patients showed a decrease (p<0.01) in mean RFonh. We conclude that RFonh elicited by chromatic equiluminant flicker is abnormally reduced in OHT and EOAG patients indicating an impairment of the parvo-cellular-mediated vasoactivity. This decrease of vascular response may occur independently of neural activity loss early in the disease process.

Multiple-Field Approach for Aberration Correction in Miniature Imaging Systems Based on Wafer-Level Production

In mobile imaging systems, the most difficult element to integrate is the objective lens. Here we present an intermediate approach between the costly traditional objectives and the low-resolution objectives inspired by the compound eyes of insects. Our multi-field approach uses a small number of optical channels each imaging a portion of the desired field of view. The full-field image is reconstructed digitally. The optics of each channel is kept simple for wafer-level fabrication and its size is sufficient to obtain a reasonable resolution. We present the design and fabrication of a prototype using 9 plano-convex lenses for 9 channels. Glass lenses glued on a wafer are used to image a full-field of ±40° with an f-number of 3. The images obtained shows field curvature correction. A simple image reconstruction scheme is presented. In conclusion, multi-field objectives fabricated with micro-optics technology are thin, simple to mount, robust, and easily replicated.

Adaptation of the Zernike's Phase-Contrast Method for Retinal Imaging

An illumination suitable for phase imaging of the retina is proposed. Using this geometry we obtained images from glass objects and retinal samples. In situ phase imaging of the retina appears to be feasible.