The neuro-ocular effects of long-duration spaceflight have been termed Spaceflight Associated Neuro-Ocular Syndrome (SANS) and are a potential challenge for future, human space exploration. The underlying pathogenesis of SANS remains ill-defined, but several emerging translational applications of terrestrial head-mounted, visual assessment technology and machine learning frameworks are being studied for potential use in SANS. To develop such technology requires close consideration of the spaceflight environment which is limited in medical resources and imaging modalities. This austere environment necessitates the utilization of low mass, low footprint technology to build a visual assessment system that is comprehensive, accessible, and efficient. In this paper, we discuss the unique considerations for developing this technology for SANS and translational applications on Earth. Several key limitations observed in the austere spaceflight environment share similarities to barriers to care for underserved areas on Earth. We discuss common terrestrial ophthalmic diseases and how machine learning and visual assessment technology for SANS can help increase screening for early intervention. The foundational developments with this novel system may help protect the visual health of both astronauts and individuals on Earth. 

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Terrestrial health applications of visual assessment technology and machine learning in spaceflight associated neuro-ocular syndrome

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http://manuscript.elsevier.com/S0039625722000480/pdf/S0039625722000480.pdf

Neuro-ophthalmic Imaging and Visual Assessment Technology for Spaceflight Associated Neuro-ocular Syndrome (SANS).

The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA's globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique "fingerprint" or "biomarker" vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.

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Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis.

The human body undergoes many changes during long-duration spaceflight including musculoskeletal, visual, and behavioral changes. Several of these microgravity-induced effects serve as potential barriers to future exploration missions. The advent of artificial intelligence (AI) in medicine has progressed rapidly and has many promising applications for maintaining and monitoring astronaut health during spaceflight. However, the austere environment and unique nature of spaceflight present with challenges in successfully training and deploying successful systems for upholding astronaut health and mission performance. In this article, the dynamic barriers facing AI development in space medicine are explored. These diverse challenges range from limited astronaut data for algorithm training to ethical/legal considerations in deploying automated diagnostic systems in the setting of the medically limited space environment. How to address these challenges is then discussed and future directions for this emerging field of research.

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Challenges of Artificial Intelligence in Space Medicine

Purpose Ocular structural and functional changes, collectively termed spaceflight-associated neuro-ocular syndrome (SANS), have been described in astronauts undergoing long-duration missions in the microgravity environment of the International Space Station. We tested the hypothesis that retinal vascular remodeling, particularly by smaller vessels, mediates the chronic headward fluid shifts associated with SANS. Methods As a retrospective study, arterial and venous patterns extracted from 30° infrared Heidelberg Spectralis retinal images of eight crew members acquired before and after six-month missions were analyzed with NASA's recently released VESsel GENeration Analysis (VESGEN) software. Output parameters included the fractal dimension and overall vessel length density that was further classified into large and small vascular branching generations. Vascular results were compared with SANS-associated clinical ocular measures. Results Significant postflight decreases in Df, Lv, and in smaller but not larger vessels were quantified in 11 of 16 retinas for arteries and veins (P value for Df, Lv, and smaller vessels in all 16 retinas were ≤0.033). The greatest vascular decreases occurred in the only retina displaying clinical evidence of SANS by choroidal folds and optic disc edema. In the remaining 15 retinas, decreases in vascular density from Df and Lv ranged from minimal to high by a custom Subclinical Vascular Pathology Index. Conclusions Together with VESGEN, the Subclinical Vascular Pathology Index may represent a new, useful SANS biomarker for advancing the understanding of SANS etiology and developing successful countermeasures for long duration space exploration in microgravity, although further research is required to better characterize retinal microvascular adaptations.

Decreased Vascular Patterning in the Retinas of Astronaut Crew Members as New Measure of Ocular Damage in Spaceflight-Associated Neuro-ocular Syndrome.

The Spaceflight Associated Neuro-ocular Syndrome (SANS), associated with the headward fluid shifts incurred in microgravity during long-duration missions, remains a high-priority health and performance risk for human space exploration. To help characterize the pathophysiology of SANS, NASA’s VESsel GENeration Analysis (VESGEN) software was used to map and quantify vascular adaptations in the retina before and after 70 days of bed rest at 6-degree Head-Down Tilt (HDT), a well-studied microgravity analog. Results were compared to the retinal vascular response of astronauts following 6-month missions to the International Space Station (ISS). By mixed effects modeling, the trends of vascular response were opposite. Vascular density decreased significantly in the 16 retinas of eight astronauts and in contrast, increased slightly in the ten retinas of five subjects after HDT (although with limited significance). The one astronaut retina diagnosed with SANS displayed the greatest vascular loss. Results suggest that microgravity is a major variable in the retinal mediation of fluid shifts that is not reproduced in this HDT bed rest model.

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Nicole M. Jacobs

Papers

Decreased Vascular Patterning in the Retinas of Astronaut Crew Members as New Measure of Ocular Damage in Spaceflight-Associated Neuro-ocular Syndrome.

Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis.

Opposite response of blood vessels in the retina to 6° head-down tilt and long-duration microgravity.