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At least 397 records · Page 22

Textureless Macula Swelling Detection with Multiple Retinal Fundus Images

Retinal fundus images acquired with non-mydriatic digital fundus cameras are a versatile tool for the diagnosis of various retinal diseases. Because of the ease of use of newer camera models and their relatively low cost, these cameras can be employed by operators with limited training for telemedicine or Point-of-Care applications. We propose a novel technique that uses uncalibrated multiple-view fundus images to analyse the swelling of the macula. This innovation enables the detection and quantitative measurement of swollen areas by remote ophthalmologists. This capability is not available with a single image and prone to error with stereo fundus cameras. We also present automatic algorithms to measure features from the reconstructed image which are useful in Point-of-Care automated diagnosis of early macular edema, e.g., before the appearance of exudation. The technique presented is divided into three parts: first, a preprocessing technique simultaneously enhances the dark microstructures of the macula and equalises the image; second, all available views are registered using non-morphological sparse features; finally, a dense pyramidal optical flow is calculated for all the images and statistically combined to build a naiveheight- map of the macula. Results are presented on three sets of synthetic images and two sets of real world images. These preliminary tests show the ability to infer a minimum swelling of 300 microns and to correlate the reconstruction with the swollen location.

60 APPLIED LIFE SCIENCES↗

Automated identification of retinal vessels using a multiscale directional contrast quantification (MDCQ) strategy

Purpose: A novel algorithm is presented to automatically identify the retinal vessels depicted in color fundus photographs. Methods: The proposed algorithm quantifies the contrast of each pixel in retinal images at multiple scales and fuses the resulting consequent contrast images in a progressive manner by leveraging their spatial difference and continuity. The multiscale strategy is to deal with the variety of retinal vessels in width, intensity, resolution, and orientation; and the progressive fusion is to combine consequent images and meanwhile avoid a sudden fusion of image noise and/or artifacts in space. To quantitatively assess the performance of the algorithm, we tested it on three publicly available databases, namely, DRIVE, STARE, and HRF. The agreement between the computer results and the manual delineation in these databases were quantified by computing their overlapping in both area and length (centerline). The measures include sensitivity, specificity, and accuracy. Results: For the DRIVE database, the sensitivities in identifying vessels in area and length were around 90% and 70%, respectively, the accuracy in pixel classification was around 99%, and the precisions in terms of both area and length were around 94%. For the STARE database, the sensitivities in identifying vessels were around 90% in area and 70% in length, and the accuracy in pixel classification was around 97%. For the HRF database, the sensitivities in identifying vessels were around 92% in area and 83% in length for the healthy subgroup, around 92% in area and 75% in length for the glaucomatous subgroup, around 91% in area and 73% in length for the diabetic retinopathy subgroup. For all three subgroups, the accuracy was around 98%. Conclusions: The experimental results demonstrate that the developed algorithm is capable of identifying retinal vessels depicted in color fundus photographs in a relatively reliable manner.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

TU-F-CAMPUS-T-02: Monte Carlo Evaluation of Kilovoltage Radiosurgery with AuNPs for Age Related Macular Degeneration (AMD)

Purpose: To evaluate the benefit of gold nanoparticles (AuNP) in radiosurgery of Age related Macular Degeneration (AMD) using Monte Carlo (MC) simulation. AMD disease causes vision loss due to a leaky vasculature of the endothelial cells. Radiosurgical therapy aims to destroy this vasculature while minimizing the delivered dose to healthy tissues of the eye. AuNP known to enhance local dose have been targeted to the macular choroidal endothelial cells to increase the therapeutic efficacy. Methods: Dose enhancement ratio (DER) in macula endothelial cells due to a thin layer of AuNP has been calculated by a MC radiation transport simulation. AuNP layer (10–100nm) has been placed on the bottom of the macula at 2.4cm depth in a water parallelepiped 3×3×6cm3. This layer has been modeled considering various concentrations of AuNP ranging from 5.5–200mg per gram of endothelial cell (volume 10×10×2um3). The x-ray source is 100kVp 4mm diameter beam tilted 0°-30° with respect to the lens. Results: DER in endothelial cell for AuNP concentration of 31mg/g (shown experimentally feasible) and 10–100nm sizes is about 1.8. Tilting 4mm-beam does not reduce the enhancement but allows to avoid the surrounding tissues. Dose distribution in the AuNP vicinity has a significant increase within 30um, peaked at AuNP interface. DER inside and outside of the irradiation 4mm-field are the same while the actual delivered dose is more than one order of magnitude lower outside the field. Compared to 100kVp, usage of filtered spectra with enhanced flux in the region 20keV-40keV shows further increase of DER by about 20%. Dose to the neighboring organs such as retina/optic nerve are reduced accordingly. Conclusion: The results of this MC simulation provide further confirmation of the potential to enhance DER with AuNP from previous analytical calculations. This study provides impetus to improve treatment effectiveness of AMD disease with radiotherapy.

60 APPLIED LIFE SCIENCES↗

Vitreal Ocygenation in Retinal Ischemia Reperfusion

PURPOSE. To study the feasibility of anterior vitreal oxygenation for the treatment of acute retinal ischemia. METHODS. Twenty rabbits were randomized into an oxygenation group, a sham treatment group, and a no treatment group. Baseline electroretinography (ERG) and preretinal oxygen (PO2) measurements were obtained 3 to 5 days before surgery. Intraocular pressure was raised to 100 mm Hg for 90 minutes and then normalized. The oxygenation group underwent vitreal oxygenation for 30 minutes using intravitreal electrodes. The sham treatment group received inactive electrodes for 30 minutes while there was no intervention for the no treatment group. Preretinal PO2 in the posterior vitreous was measured 30 minutes after intervention or 30 minutes after reperfusion (no treatment group) and on postoperative days (d) 3, 6, 9, and 12. On d14, rabbits underwent ERG and were euthanatized.

60 APPLIED LIFE SCIENCES↗

A Trans -Acting Protein Effect Causes Severe Eye Malformation in the Mp Mouse

Mp is an irradiation-induced mouse mutation associated with microphthalmia, micropinna and hind limb syndactyly. We show that Mp is caused by a 660 kb balanced inversion on chromosome 18 producing reciprocal 3-prime gene fusion events involving Fbn2 and Isoc1. The Isoc1-Fbn2 fusion gene (Isoc1 Mp ) mRNA has a frameshift and early stop codon resulting in nonsense mediated decay. Homozygous deletions of Isoc1 do not support a significant developmental role for this gene. The Fbn2-Isoc1 fusion gene (Fbn2 Mp ) predicted protein consists of the N-terminal Fibrillin-2 (amino acids 1–2646, exons 1– 62) lacking the C-terminal furin-cleavage site with a short out-of-frame extension encoded by the final exon of Isoc1. The Mp limb phenotype is consistent with that reported in Fbn2 null embryos. However, severe eye malformations, a defining feature of Mp, are not seen in Fbn2 null animals. Fibrillin-2 Mp forms large fibrillar structures within the rough endoplasmic reticulum (rER) associated with an unfolded protein response and quantitative mass spectrometry shows a generalised defect in protein secretion in conditioned media from mutant cells. In the embryonic eye Fbn2 is expressed within the peripheral ciliary margin (CM). Mp embryos show reduced canonical Wnt-signalling in the CM – known to be essential for ciliary body development - and show subsequent aplasia of CM-derived structures. We propose that the Mp ‘‘worse-than-null’’ eye phenotype plausibly results from a failure in normal trafficking of proteins that are co-expressed with Fbn2 within the CM. The prediction of similar trans-acting protein effects will be an important challenge in the medical interpretation of human mutations from whole exome sequencing.

59 BASIC BIOLOGICAL SCIENCES↗

The ASAC Flight Segment and Network Cost Models

To assist NASA in identifying research art, with the greatest potential for improving the air transportation system, two models were developed as part of its Aviation System Analysis Capability (ASAC). The ASAC Flight Segment Cost Model (FSCM) is used to predict aircraft trajectories, resource consumption, and variable operating costs for one or more flight segments. The Network Cost Model can either summarize the costs for a network of flight segments processed by the FSCM or can be used to independently estimate the variable operating costs of flying a fleet of equipment given the number of departures and average flight stage lengths.

Kaplan, Bruce J.↗

Aircraft/Air Traffic Management Functional Analysis Model: Technical Description

The Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 (FAM 2.0), is a discrete event simulation model designed to support analysis of alternative concepts in air traffic management and control. FAM 2.0 was developed by the Logistics Management Institute (LMI) under a National Aeronautics and Space Administration (NASA) contract. This document provides a technical description of FAM 2.0 and its computer files to enable the modeler and programmer to make enhancements or modifications to the model. Those interested in a guide for using the model in analysis should consult the companion document, Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 Users Manual.

Etheridge, Melvin↗

Aircraft/Air Traffic Management Functional Analysis Model: User's Guide - Version 2.0

The Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 (FAM 2.0), is a discrete event simulation model designed to support analysis of alternative concepts in air traffic management and control. FAM 2.0 was developed by the Logistics Management Institute (LMI) a National Aeronautics and Space Administration (NASA) contract. This document provides a guide for using the model in analysis. Those interested in making enhancements or modification to the model should consult the companion document, Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 Technical Description.

Etheridge, Melvin↗

Retinal Image Quality Assessment for Spaceflight-Induced Vision Impairment Study

Long-term exposure to space microgravity poses significant risks for visual impairment. Evidence suggests such vision changes are linked to cephalad fluid shifts, prompting a need to directly quantify microgravity-induced retinal vascular changes. The quality of retinal images used for such vascular remodeling analysis, however, is dependent on imaging methodology. For our exploratory study, we hypothesized that retinal images captured using fluorescein imaging methodologies would be of higher quality in comparison to images captured without fluorescein. A semi-automated image quality assessment was developed using Vessel Generation Analysis (VESGEN) software and MATLAB® image analysis toolboxes. An analysis of ten images found that the fluorescein imaging modality provided a 36% increase in overall image quality (two-tailed p=0.089) in comparison to nonfluorescein imaging techniques.

retina↗

Analysis by NASA's VESGEN Software of Retinal Blood Vessels Before and After 70-Day Bed Rest: A Retrospective Study

Significant risks for visual impairment associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. Impairments include decreased near visual acuity, posterior globe flattening, choroidal folds, optic disc edema and cotton wool spots. We hypothesize that microgravity-induced fluid shifts result in pathological changes within the retinal blood vessels that precede development of visual and other ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASAs innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) head-down tilt in human subjects before and after 70 days of bed rest, and (2) U.S. crew members before and after ISS missions. VESGEN analysis in previous research supported by the US National Institutes of Health identified surprising new opportunities to regenerate retinal vessels during early-stage, potentially reversible progression of the visually impairing and blinding disease, diabetic retinopathy.

Vascular↗

Association Between Increased Vascular Density and Loss of Protective RAS in Early-stage NPDR

Our hypothesis predicts that retinal blood vessels increase in density during early-stage progression to moderate nonproliferative diabetic retinopathy (NPDR). The renin-angiotensin system (RAS) is implicated in the pathogenesis of DR and in the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population that is instrumental in vascular repair.

Fractal↗

Impact of The Protective Renin-Angiotensin System (RAS) on The Vasoreparative Function of CD34+ CACs in Diabetic Retinopathy

Purpose: In diabetes, the impaired vasoreparative function of Circulating Angiogenic Cells (CACs) is believed to contribute to the progression of diabetic retinopathy (DR). Accumulating evidence suggests that the protective arm of renin-angiotensin system (RAS) ACE2 Angiotensin-(1-7) Mas plays an important role in restoring the function of diabetic CACs. We examined the protective RAS in CACs in diabetic individuals with different stages of retinopathy. Methods: Study subjects (n43) were recruited as controls or diabetics with either no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR or proliferative DR (PDR). Fundus photography and fluorescein angiograms were analyzed using Vessel Generation Analysis (VESGEN) software in a cohort of subjects. CD34+ CACs were isolated from peripheral blood of diabetics and control subjects. RAS gene expressions in CACs were measured by qPCR. The vasoreparative function of CACs was assessed by migration ability toward CXCL12 using the QCM 5M 96-well chemotaxis cell migration assay. Results: ACE2 gene is a key enzyme converting the deleterious Angiotensin II to the beneficial Angiotensin-(1-7). ACE2 expression in CACs from diabetic subjects without DR was increased compared to controls, suggestive of compensation (p0.0437). The expression of Mas (Angiotensin-(1-7) receptor) in CACs was also increased in diabetics without DR, while was reduced in NPDR compared to controls (p0.0002), indicating a possible loss of compensation of the protective RAS at this stage of DR. The presence of even mild NPDR was associated with CD34+ CAC migratory dysfunction. When pretreating CACs of DR subjects with Angiotensin-(1-7), migratory ability to a chemoattractant CXCL12 was restored (p0.0008). By VESGEN analysis, an increase in small vessel density was observed in NPDR subjects when compared with the controls. Conclusions: These data suggest the protective RAS axis within diabetic CACs may help maintain their vasoreparative potential. The VESGEN analysis supports the presence of retinal repair in small vessels. The loss of the protective arm of RAS may predict the progression of DR.

diabetes↗