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All sourcesNASA NTRSDOE OSTI
NASA NTRS2016

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↗
NASA NTRS2018

Differences in Pre and Post Vascular Patterning of Retinas from ISS Crew Members and HDT Subjects by VESGEN Analysis

Accelerated research by NASA [1] has investigated the significant risks for visual and ocular impairments Spaceflight Associated Neuro-Ocular Syndrome /Visual Impairment/Intracranial Pressure (SANS/VIIP) incurred by microgravity spaceflight, especially long-duration missions. Our study investigates the role of blood vessels in the incidence and etiology of SANS/VIIP within the retinas of Astronaut crewmembers pre-and post-flight to the International Space Station (ISS) by NASA's VESsel GENeration Analysis (VESGEN). The response of retinal vessels in crewmembers to microgravity was compared to that of retinal vessels to Head-Down Tilt (HDT) in subjects undergoing 70-Day Bed Rest. The study tests the proposed hypothesis that cephalad fluid shifts missions, resulting in ocular and visual impairments, are necessarily mediated in part by retinal blood vessels, and are therefore accompanied by significant remodeling of retinal vasculature.Vascular patterns in the retinas of crew members and HDTBR subjects extracted from 30° infrared (IR) Heidelberg Spectralis® images collected pre/postflight and pre/post HDTBR, respectively, were analyzed by VESGEN (patent pending). a mature, automated software developed as a research discovery tool for progressive vascular diseases in the retina and other tissues [2]. The weighted, multi-parametric VESGEN analysis generates maps of branching arterial and venous trees and quantification by parameters such as the fractal dimension (Df, a modern measure of vascular space-filling capacity), vessel diameters, and densities of vessel length and number classified into specific branching generations by vascular physiological branching rules [2,3]. The retrospective study approved by NASA’s Institutional Review Board included six HDT subjects (NASA Flight Analogs Research Unit [FARU] Campaign 11; for example, [4]) and eight ISS crewmembers monitored by routine occupational surveillance who provided their study consents to NASA’s Lifetime Surveillance of Astronaut Health (LSAH). For the initial blinded VESGEN phase, ophthalmic retinal images were masked as to subject identity and pre- and post-status. In the second unblinded phase, VESGEN results were analyzed according to the pre- and post-status of left and right retinas matched to each subject. To complete our study, vascular results will be subjected to NASA biostatistical analysis and correlated with other ophthalmic and medical findings. Preliminary results for changes in the pre- to post-status of vascular patterning in the retinas of crewmembers and HDT subjects are strikingly opposite. By Df and other vascular branching measures, the space-filling capacity of arterial and venous trees decreased in a substantial subset of crewmembers (11/16 retinas). In contrast, vascular densities increased in a substantial subset of HDT subjects by the same parameters (6/10 retinas, currently excluding one anomalous subject). To conclude the study, biostatistical and medical analyses will be of critical importance for investigating the validity of these vascular findings. Vascular densities appeared to decrease in the retinas of crewmembers following ISS Missions, and increase in subjects after HDT. The vascular increases and decreases most likely derive primarily from limits of resolution to the ophthalmic imaging that does not capture the smallest vessels, rather than from vessel growth or atrophy. Differences in arterial and venous response to cephalad fluid shifts induced by ISS and HDT may have resulted from a long-duration conditioning phenomenon (for example, 6-month ISS missions compared to 70-day HDT), or the presence of gravity in HDT compared to microgravity onboard the ISS. To conclude our study, the biostatistical and medical analyses will be of critical importance for investigating the validity and significance of the VESGEN findings.

Murray, M. C.↗
NASA NTRS2017

Analysis by NASA's VESGEN Software of Retinal Blood Vessels in Human Subjects Undergoing Head-Down Tilt During 70-Day Bed Rest

Significant risks for visual impairment associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions [1]. We hypothesize that microgravity-induced fluid shifts result in pathological changes within blood vessels of the retina that precede development of visual and other ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated for two studies in 30deg infrared (IR) Heidelberg Spectralis(Registered Trademark) images with NASA's innovative VESsel GENeration Analysis (VESGEN) software [2,3]. The retrospective studies include: (1) before, during and after (pre, mid and post) 6º head-down tilt (HDT) in human subjects during 70 days of bed rest, and (2) before and after missions to the International Space Station (ISS) by U.S. crew members. Results for both studies are almost complete. A preliminary example for HDT is described below.

Microgravity↗
NASA NTRS2018

Differences in Pre and Post Vascular Patterning Within Retinas from ISS Crew Members and Head-Down Tilt (HDT) Subjects by VESGEN Analysis

Accelerated research by NASA has investigated the significant risks incurred during long-duration missions in microgravity for Space Flight-Associated Neuro-ocular Syndrome (SANS, formerly known as Visual Impairments associated with Increased Intracranial Pressure, VIIP) [1]. For our study, NASA's VESsel GENeration Analysis (VESGEN) was used to investigate the role of retinal blood vessels in the etiology of SANS/VIIP. The response of retinal vessels to microgravity was evaluated in astronaut crew members pre and post flight to the International Space Station (ISS), and compared to the response of retinal vessels in healthy volunteers to 6deg head-down tilt during 70 days of bed rest (HDTBR). For the study, we are testing the hypothesis that long-term cephalad fluid shifts resulting in ocular and visual impairments are necessarily mediated in part by retinal blood vessels, and therefore are accompanied by structural adaptations of the vessels. METHODS: Vascular patterns in the retinas of crew members and HDTBR subjects extracted from 30deg infrared (IR) Heidelberg Spectralis images collected pre/postflight and pre/post HDTBR, respectively, were analyzed by VESGEN (patent pending). VESGEN is a mature, automated software developed as a research discovery tool for progressive vascular diseases in the retina and other tissues. The multi-parametric VESGEN analysis generates maps of branching arterial and venous trees quantified by parameters such as the fractal dimension (Df, a modern measure of vascular space-filling capacity), vessel diameters, and densities of vessel length and number classified into specific branching generations according to vascular physiological branching rules. The retrospective study approved by NASA's Institutional Review Board included the analysis of bilateral retinas in eight ISS crew members monitored by routine occupational surveillance and six HDTBR subjects (NASA FARU Campaign 11, for example). The VESGEN analysis was conducted in a blinded fashion, with IR retinal images masked to the subject's identity, ophthalmic and clinical characteristics, and to the temporal sequence of image collection. To complete our study, VESGEN results will be analyzed statistically and correlated with other ophthalmic and medical findings. RESULTS: Preliminary results for changes in the pre to post status of vascular patterning in the retinas of crew members and HDTBR subjects are interestingly opposite. By Df and other vascular branching measures, the space-filling capacity of arterial and venous trees decreased in the majority of crew members (11/16 retinas). In contrast, vascular densities increased in HDTBR subjects by the same parameters (6/10 retinas). To conclude the study, biostatistics and medical analyses will be conducted to quantify and draw conclusions about how the changes associated with flight compare to those associated with HDTBR. CONCLUSIONS: Vascular densities appeared to decrease in the retinas of ISS crew members and increase in HDTBR subjects. Differences in arterial and venous response to cephalad fluid shifts induced by ISS and HDTBR may have resulted from a long-duration conditioning phenomenon (for example, 6-month ISS missions compared to 70 days HDTBR), or the presence of gravity in HDTBR compared to microgravity on the ISS. In addition, increased and decreased vessel diameters for Crew Members and HDTBR, respectively, are subject to limits of im

Vascular↗
NASA NTRS2012

New Therapeutic Window of Regenerative Opportunity in Diabetic Retinopathy by VESGEN Analysis

Vascular pattern may serve as a useful new biomarker principle of complex, multi-scale signaling in pathological, physiological angiogenesis and microvascular remodeling. Each angiogenesis stimulator or inhibitor we have analyzed, including VEGF, bFGF, TGF-beta1, angiostatin and triamcinolone acetonide, has induced a novel "fingerprint" or "signature" biomarker vascular pattern that is spatio-temporally unique. Remodeling vasculature thereby provides an informative read-out of dominant molecular signaling, when analyzed by innovative, fractal-based VESsel GENeration (VESGEN) Analysis software. Using VESGEN to analyze ophthalmic clinical vascular images, we recently introduced a potential paradigm shift to the understanding of early-stage progression that suggests new regenerative opportunities for human diabetic retinopathy (DR), the major blinding disease for working-aged adults. In a pilot study, we discovered that angiogenesis oscillates as a surprising, homeostatic-like regeneration of retinal vessels during early progression of DR (IOVS 51(1):498). Results suggest that the term non-proliferative DR may be a misnomer. In new studies, normalization of the vasculature will be determined from the response of vascular pattern to therapeutic monitoring and treatment. We have mapped and quantified in vivo experimental models of angiogenesis, lymphangiogenesis and intravital blood flow from cellular/molecular to higher systems levels that include a murine model of infant retinopathy of prematurity (ROP); developing and pathological coronary and placental-like vessel models; progressive intestinal inflammation, growing murine tumors, and other pathological, physiological and therapeutically treated tissues of transgenic mice and avian embryos. Vascular Alterations, Visual Impairments (VIIP) & Increased Intracranial Pressure (ICP), Immunosuppression & Bone Loss: NASA-defined risk categories for human space exploration and ISS Utilization

Parsons-Wingert, Patricia A.↗
NASA NTRS2014

Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity Status Report: Optimization of Rat Retina Flat Mounts Staining to Study Vascular Remodeling

Preliminary data from a prior tissue‐sharing experiment has suggested that early growth response protein‐1 (Egr1), a transcription factor involved in various stress responses in the vasculature, is induced in the rat retina after 14 days of hindlimb suspension (HS) and may be evidence that mechanical stress is occurring secondary to the cephalad fluid shift. This mechanical stress could cause changes in oxygenation of the retina, and the subsequent ischemia‐ or inflammation‐driven hypoxia may lead to microvascular remodeling. This microvascular remodeling process can be studied using image analysis of retinal vessels and can be then be quantified by the VESsel GENeration Analysis (VESGEN) software, a computational tool that quantifies remodeling patterns of branching vascular trees and capillary or vasculogenic networks. Our project investigates whether rodent HS is a valid model to study the effects of simulated‐weightlessness on ocular structures and their relationship with intracranial pressure (ICP). One of the hypotheses to be tested is that HS‐induced cephalad fluid shift is accompanied by vascular engorgement that produces changes in retinal oxygenation, leading to oxidative stress, hypoxia, microvascular remodeling, and cellular degeneration. We have optimized the procedure to obtain flat mounts of rat retina, staining of the endothelial lining in vasculature and acquisition of high quality images suitable for VESGEN analysis. Briefly, eyes were fixed in 4% paraformaldehyde for 24 hours and retinas were detached and then mounted flat on microscope slides. The microvascular staining was done with endothelial cell‐specific isolectin binding, coupled to Alexa‐488 fluorophore. Image acquisition at low magnification and high resolution was performed using a new Leica SP8 confocal microscope in a tile pattern across the X,Y plane and multiple sections along the Z‐axis. This new confocal microscope has the added capability of dye separation using the Linear Unmixing method and allows us to remove the autofluorescence originating from the photoreceptor layer. In summary, we have an improved method for studying the retinal microvasculature that will provide an increase in the quality of images captured and will be applied throughout the various animal cohorts of the recentlyinitiated study that will evaluate rodent HS as a model to study ophthalmic complications in microgravity.

Theriot, Corey A.↗
NASA NTRS2016

Analysis by NASA's VESGEN Software of Vascular Branching in the Human Retina with a Ground-Based Microgravity Analog

Significant risks for visual impairment were discovered recently in astronauts following spaceflight, especially after long-duration missions.1 We hypothesize that microgravity-induced fluid shifts result in pathological changes within the retinal vasculature that precede visual and other ocular impairments. We therefore are analyzing retinal vessels in healthy subjects with NASA's VESsel GENeration Analysis (VESGEN) software2 before and after head-down tilt (HDT), a ground-based microgravity analog For our preliminary study of masked images, two groups of venous trees with and without small veins (G≥7) were clearly identified by VESGEN analysis. Upon completing all images and unmasking the subject status of pre- and post- HDT, we will determine whether differences in the presence or absence of small veins are important correlates, and perhaps reliable predictors, of other ocular and physiological adaptations to prolonged HDT and microgravity. Greater peripapillary retinal thickening was measured following 70-day HDT bed rest than 14-day HDT bed rest, suggesting that time of HDT may increase the amount of optic disc swelling.3 Spectralis OCT detected retinal nerve fiber layer thickening post HDT, without clinical signs of optic disc edema. Such changes may have resulted from HDT-induced cephalad fluid shifts. Clinical methods for examining adaptive microvascular remodeling in the retina to microgravity space flight are currently not established.

Retina↗
NASA NTRS1999

Late ophthalmological complications after total body irradiation in non-human primates

PURPOSE: To investigate the long-term effects of total body irradiation (TBI) on the incidence and time course of ocular complications. MATERIALS AND METHODS: Rhesus monkeys treated with TBI photon doses up to 8.5 Gy and proton doses up to 7.5 Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. RESULTS: Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photon-doses of 8 and 8.5 Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. CONCLUSIONS: Radiation alone for doses up to 8.5 Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5 Gy and proton doses in excess of 2.5 Gy.

NASA Discipline Radiation Health↗
NASA NTRS1973

Effect of elimination of nitrogen and/or hypoxia or restricted visual environment on color vision and range of accommodation

The effects upon range of accommodation and color vision of reduced atmospheric pressure, at partial and complete elimination of nitrogen, of hypoxia, and of exposure for varying periods of time to restricted visual environment, have been studied alone or in various combinations. Measurements were made on the electroretinogram, the electrooculogram, and the diameter of the retinal vessels as an indicator of blood flow to the retina at the time of total elimination of nitrogen. An objective method was used to test range of accommodation. In the color vision test the flicker colors of a Benham's top were matched with a colorimeter.

Wolbarsht, M. L.↗
NASA NTRS1993

Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt

Spaceflight induces a cephalad redistribution of fluid volume and blood flow within the human body, and space motion sickness, which is a problem during the first few days of space flight, could be related to these changes in fluid status and in blood flow of the cerebrum and vestibular system. To evaluate possible changes in cerebral blood flow during simulated weightlessness, we measured blood velocity in the middle cerebral artery (MCA) along with retinal vascular diameters, intraocular pressure, impedance cardiography, and sphygmomanometry on nine men (26.2 +/- 6.6 yr) morning and evening for 2 days during continuous 10 deg head-down tilt (HDT). When subjects went from seated to head-down bed rest, their heart rate and retinal diameters decreased, and intraocular pressures increased. After 48 h of HDT, blood flow velocity in the MCA was decreased and thoracic impedance was increased, indicating less fluid in the thorax. Percent changes in blood flow velocities in the MCA after 48 h of HDT were inversely correlated with percent changes in retinal vascular diameters. Blood flow velocities in the MCA were inversely correlated (intersubject) with arterial pressures and retinal vascular diameters. Heart rate, stroke volume, cardiac output, systolic arterial pressure, and at times pulse pressure and blood flow velocities in the MCA were greater in the evening. Total peripheral resistance was higher in the morning. Although cerebral blood velocity is reduced after subjects are head down for 2 days, the inverse relationship with retinal vessel diameters, which have control analogous to that of cerebral vessels, indicates cerebral blood flow is not reduced.

Frey, Mary A. B.↗
NASA NTRS2015

Modeling the Effects of Spaceflight on the Posterior Eye in VIIP

Purpose: Visual Impairment and Intracranial Pressure (VIIP) syndrome is a new and significant health concern for long-duration space missions. Its etiology is unknown, but is thought to involve elevated intracranial pressure (ICP)that induces connective tissue changes and remodeling in the posterior eye (Alexander et al. 2012). Here we study the acute biomechanical response of the lamina cribrosa (LC) and optic nerve to elevations in ICP utilizing finite element (FE) modeling. Methods: Using the geometry of the posterior eye from previous axisymmetric FE models (Sigal et al. 2004), we added an elongated optic nerve and optic nerve sheath, including the pia and dura. Tissues were modeled as linear elastic solids. Intraocular pressure and central retinal vessel pressures were set at 15 mmHg and 55 mmHg, respectively. ICP varied from 0 mmHg (suitable for standing on earth) to 30 mmHg (representing severe intracranial hypertension, thought to occur in space flight). We focused on strains and deformations in the LC and optic nerve (within 1 mm of the LC) since we hypothesize that they may contribute to vision loss in VIIP. Results: Elevating ICP from 0 to 30 mmHg significantly altered the strain distributions in both the LC and optic nerve (Figure), notably leading to more extreme strain values in both tension and compression. Specifically, the extreme (95th percentile) tensile strains in the LC and optic nerve increased by 2.7- and 3.8-fold, respectively. Similarly, elevation of ICP led to a 2.5- and 3.3-fold increase in extreme (5th percentile) compressive strains in the LC and optic nerve, respectively. Conclusions: The elevated ICP thought to occur during spaceflight leads to large acute changes in the biomechanical environment of the LC and optic nerve, and we hypothesize that such changes can activate mechanosensitive cells and invoke tissue remodeling. These simulations provide a foundation for more comprehensive studies of microgravity effects on human vision, e.g. to guide biological studies in which cells and tissues are mechanically loaded in a ranger elevant for microgravity conditions.

gravitational physiology↗
NASA NTRS2016

Analysis of Retinal Vascular Branching in Human Subjects Undergoing 70-Day Head-Down Tilt by NASAs VESGEN Software

Significant risks for visual impairment were discovered recently in astronauts following spaceflight, especially after long-duration missions. We hypothesize that microgravity-induced fluid shifts result in pathological changes within the retinal vasculature that precede visual and other ocular impairments. We therefore are analyzing retinal vessels in healthy subjects before and after head-down tilt (HDT), a ground-based microgravity analog with NASA's VESsel GENeration Analysis (VESGEN) software. Methods. Spectralis® infrared (IR) fundus images were collected from both eyes of 6 subjects before and after 70 days of bed rest at 6 degree HDT (NASA Campaign 11). For our retrospective study, branching patterns in arterial and venous trees are mapped by VESGEN into vessel branching generations (Gx) that are quantified by parameters such as densities of vessel length (Lv), area (Av), number (Nv) and fractal dimension (Df) as described previously for diabetic retinopathy (IOVS 51(1):498). Results are further assigned by VESGEN into groups of large (G1-3), medium (G4-6) and small (G≥7) vessels. Results. All subjects remained asymptomatic throughout duration of HDT. To date, we have analyzed one IR image from each of the 12 eyes. Interestingly, two groups of the masked study population identified by VESGEN are distinguished by the presence or absence of small veins (G≥7). For example, L≥7 and Av≥7 are 2.7+/-1.3 E-4 px/px2 and 7.2+/-3.6 E-4 px2/px2 in 6 retinas, but 0 in the other 6 retinas. Nonetheless, the space-filling properties of the entire venous trees were remarkably uniform by all parameters, such as Df = 1.56+/-0.02 for 6 retinas with G≥7 and 1.55+/-0.02 for retinas without G≥7. No small arteries (G≥7) were detected. Conclusions. For our preliminary masked analysis, two groups of venous trees with and without small veins (G≥7) were clearly revealed by VESGEN. Upon completing all images and unmasking the subject status of before and after HDT, we will determine whether differences in the presence or absence of small veins are important correlates, and perhaps reliable predictors, of other ocular and physiological adaptations to prolonged head-down tilt and microgravity. Clinical methods for examining adaptive microvascular remodeling in the retina to microgravity space flight are not currently established.

Fractal↗
NASA NTRS2016

Probabilistic Modeling Of Ocular Biomechanics In VIIP: Risk Stratification

Visual Impairment and Intracranial Pressure (VIIP) syndrome is a major health concern for long-duration space missions. Currently, it is thought that a cephalad fluid shift in microgravity causes elevated intracranial pressure (ICP) that is transmitted along the optic nerve sheath (ONS). We hypothesize that this in turn leads to alteration and remodeling of connective tissue in the posterior eye which impacts vision. Finite element (FE) analysis is a powerful tool for examining the effects of mechanical loads in complex geometries. Our goal is to build a FE analysis framework to understand the response of the lamina cribrosa and optic nerve head to elevations in ICP in VIIP. To simulate the effects of different pressures on tissues in the posterior eye, we developed a geometric model of the posterior eye and optic nerve sheath and used a Latin hypercubepartial rank correlation coef-ficient (LHSPRCC) approach to assess the influence of uncertainty in our input parameters (i.e. pressures and material properties) on the peak strains within the retina, lamina cribrosa and optic nerve. The LHSPRCC approach was repeated for three relevant ICP ranges, corresponding to upright and supine posture on earth, and microgravity [1]. At each ICP condition we used intraocular pressure (IOP) and mean arterial pressure (MAP) measurements of in-flight astronauts provided by Lifetime Surveillance of Astronaut Health Program, NASA Johnson Space Center. The lamina cribrosa, optic nerve, retinal vessel and retina were modeled as linear-elastic materials, while other tissues were modeled as a Mooney-Rivlin solid (representing ground substance, stiffness parameter c1) with embedded collagen fibers (stiffness parameters c3, c4 and c5). Geometry creationmesh generation was done in Gmsh [2], while FEBio was used for all FE simulations [3]. The LHSPRCC approach resulted in correlation coefficients in the range of 1. To assess the relative influence of the uncertainty in an input parameter on the peak strains, we ranked and then normalized these coefficients, considering that normalized values 0.5 implied a substantial influence on the range of the peak strains in the optic nerve head (ONH). IOP and ICP were found to have a major influence on the peak strains in the ONH, as did optic nerve and LC stiffness. Interestingly, the stiffness of the sclera far from the scleral canal did not have a large influence on peak strains in ONH tissues; however, the collagen fiber stiffness in the peripapillary sclera and annular ring both influenced the peak strains within the ONH. We have created a physiologically relevant model that incorporated collagen fibers to study the effects of elevated ICP. Elevated ICP resulted in strains in the optic nerve that are not predicted to occur on earth: the upright or supine conditions. We found that IOP, ICP, lamina cribrosa stiffness and optic nerve stiffness had the highest association with these extreme strains in the ONH. These extreme strains may activate mechanosensitive cells that induce tissue remodeling and are a risk factor for the development of VIIP.

biomechanics↗
NASA NTRSDate not supplied

Retinal Image Quality Assessment for Spaceflight-Induced Visual Impairment Study

Medical reports have identified visual impairments as a risk associated with extended exposure to microgravity. Etiology of these ocular changes is currently unknown. Current hypotheses propose cephalad fluid shifts resulting from microgravity as the primary cause of ocular damage. One approach to studying ocular response to microgravity is by examining possible changes in retinal blood vessels using a NASA model of microgravity, the head-down tilt (HDT) of human subjects undergoing prolonged bed rest (BR). Retinal vessels in astronauts and BR subjects are monitored by Heidelberg Spectralis infrared (IR) imaging, in which retinal image quality is limited by insufficient resolution of small vessels. Yet small vessels respond and remodel most actively to physiological stress.For our NASA study of BR subjects, we identify retinal image quality as thecapability to capture vascular detail to acceptable resolution of small vessels. We therefore are analyzing Spectralis images acquired with fluorescein angiography(FA), where increased contrast significantly improves image resolution. The FA images are of normal subjects participating in a clinical study on diabeticretinopathy (US National Institutes of Health). We hypothesize that FA Spectralis images are of superior quality compared to non-FA Spectralis IR images.

Rodrigo Rene Rai Munoz Abujder↗
NASA NTRS1997

Image processing for improved eye-tracking accuracy

Video cameras provide a simple, noninvasive method for monitoring a subject's eye movements. An important concept is that of the resolution of the system, which is the smallest eye movement that can be reliably detected. While hardware systems are available that estimate direction of gaze in real-time from a video image of the pupil, such systems must limit image processing to attain real-time performance and are limited to a resolution of about 10 arc minutes. Two ways to improve resolution are discussed. The first is to improve the image processing algorithms that are used to derive an estimate. Off-line analysis of the data can improve resolution by at least one order of magnitude for images of the pupil. A second avenue by which to improve resolution is to increase the optical gain of the imaging setup (i.e., the amount of image motion produced by a given eye rotation). Ophthalmoscopic imaging of retinal blood vessels provides increased optical gain and improved immunity to small head movements but requires a highly sensitive camera. The large number of images involved in a typical experiment imposes great demands on the storage, handling, and processing of data. A major bottleneck had been the real-time digitization and storage of large amounts of video imagery, but recent developments in video compression hardware have made this problem tractable at a reasonable cost. Images of both the retina and the pupil can be analyzed successfully using a basic toolbox of image-processing routines (filtering, correlation, thresholding, etc.), which are, for the most part, well suited to implementation on vectorizing supercomputers.

NASA Discipline Space Human Factors↗
NASA NTRS2017

Mapping by VESGEN of Blood Vessels in the Retinas of Astronauts Pre- and Post-Flight to the ISS

Research by NASA [1] established that significant risks for visual and ocular impairments associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. It is well established in physiology and pathology that a fundamental role of the microvasculature is to mediate fluid transfers and remodel actively in response to environmental, immune and other stresses. We therefore hypothesize that remodeling of retinal blood vessels necessarily occurs during accommodation of microgravity-induced fluid shifts prior to subsequent development of visual and ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASA's innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) U.S. crew members before and after ISS missions, and (2) head-down tilt in human subjects before and after 70 days of bed rest. We anticipate that results of the two studies will be complete by the Investigators Workshop (January 22, 2017). METHODS: For the 2013 NASA NRA award, we are concluding the analysis of 30 degree infrared (IR) Heidelberg Spectralis images of retinal blood vessels by VESGEN (patents pending), a mature, automated software developed as a translational and basic vascular research discovery tool, particularly for retinal vascular disease. Subjects of our retrospective study include eight ISS crew members monitored for routine occupational surveillance pre- and post-flight, who provided their study consents to NASAs Lifetime Surveillance of Astronaut Health (LSAH) in coordination with approval of the VESGEN retrospective study protocol by NASAs Institutional Review Board (IRB). The ophthalmic retinal images (average image resolution, approximately 5.6 microns per pixel) are blinded as to pre and post ISS status until the second portion of our study, when VESGEN results will be correlated with other ophthalmic and medical findings for the crew members. Due to image resolution challenges, a novel Matlab tool was developed for aligning pre and post images, and comparing (querying) the two images for differences in the morphology of small vessels. RESULTS: During the past year, LSAH approved the release of all astronaut retinal images to our study for VESGEN analysis. Substantial progress on the initial blinded portion of the study is in place. We anticipate that VESGEN analysis of the 32 Spectralis IR retinal images will be complete for presentation at the 2017 IWS meeting. CONCLUSIONS: Modified retinal vascular patterning may offer early-stage predictions of ocular changes resulting in decreased visual acuity for the VIIP syndrome. Novel insights provided by VESGEN into progressively pathological and blinding vascular remodeling in the human retina currently help to guide other NIH- and NASA-supported therapeutic studies of retinal disease and modeling of the VIIP risk. Results of our vascular investigation of the retinas of astronauts pre- and post-flight may help advance the understanding of both healthy and pathological adaptations to fluid shifts in microgravity associated with the VIIP syndrome. Preliminary results indicate that imaging of higher resolution, such as the new OCT angiography (OCT-A) technology, will be required to determine conclusively the role of the smaller retinal and choroidal vessels in VIIP etiology.

VESGEN↗
NASA NTRS1966

Retinal vascular response to oxygen at increased partial pressures

Aside from the inverse relationship between retinal blood vessel caliber and (p)O2, there were no positive findings. In the case of the renal function and pulmonary function this is not surprising, as previous reports had led us to believe that none would occur as a result of our experimental design.

VASOCONSTRICTION↗
NASA NTRS1966

General discussion of results and conclusions

Inverse relationship between retinal blood vessel caliber and oxygen level, creatinine level variations, and buildup in microorganisms during confinement of aviators in pure oxygen

OXYGEN SYSTEM↗