Spaceflight-associated Neuro-ocular Syndrome Research Articles

Modeling the impact of thoracic pressure on intracranial pressure

A potential contribution to the progression of Spaceflight Associated Neuro-ocular Syndrome is the thoracic-to-spinal dural sac transmural pressure relationship. In this study, we utilize a lumped-parameter computational model of human cerebrospinal fluid (CSF) systems to investigate mechanisms of CSF redistribution. We present two analyses to illustrate potential mechanisms for CSF pressure alterations similar to those observed in microgravity conditions. Our numerical evidence suggests that the compliant relationship between thoracic and CSF compartments is insufficient to solely explain the observed decrease in CSF pressure with respect to the supine position. Our analyses suggest that the interaction between thoracic pressure and the cardiovascular system, particularly the central veins, has greater influence on CSF pressure. These results indicate that future studies should focus on the holistic system, with the impact of cardiovascular changes to the CSF pressure emphasized over the sequestration of fluid in the spine.

SANS-CNN: An automated machine learning technique for spaceflight associated neuro-ocular syndrome with astronaut imaging data

Spaceflight associated neuro-ocular syndrome (SANS) is one of the largest physiologic barriers to spaceflight and requires evaluation and mitigation for future planetary missions. As the spaceflight environment is a clinically limited environment, the purpose of this research is to provide automated, early detection and prognosis of SANS with a machine learning model trained and validated on astronaut SANS optical coherence tomography (OCT) images. In this study, we present a lightweight convolutional neural network (CNN) incorporating an EfficientNet encoder for detecting SANS from OCT images titled “SANS-CNN.” We used 6303 OCT B-scan images for training/validation (80%/20% split) and 945 for testing with a combination of terrestrial images and astronaut SANS images for both testing and validation. SANS-CNN was validated with SANS images labeled by NASA to evaluate accuracy, specificity, and sensitivity. To evaluate real-world outcomes, two state-of-the-art pre-trained architectures were also employed on this dataset. We use GRAD-CAM to visualize activation maps of intermediate layers to test the interpretability of SANS-CNN’s prediction. SANS-CNN achieved 84.2% accuracy on the test set with an 85.6% specificity, 82.8% sensitivity, and 84.1% F1-score. Moreover, SANS-CNN outperforms two other state-of-the-art pre-trained architectures, ResNet50-v2 and MobileNet-v2, in accuracy by 21.4% and 13.1%, respectively. We also apply two class-activation map techniques to visualize critical SANS features perceived by the model. SANS-CNN represents a CNN model trained and validated with real astronaut OCT images, enabling fast and efficient prediction of SANS-like conditions for spaceflight missions beyond Earth’s orbit in which clinical and computational resources are extremely limited.

Spaceflight-associated neuro-ocular syndrome: potential etiologies and connections to the glymphatic system.

The etiology of spaceflight-associated neuro-ocular syndrome (SANS) is a developing field of research, with many current hypotheses receiving varying degrees of support. In this article, three prominent risk factors including zero gravity conditions, extraterrestrial hypercapnic environments, and individual genetic predisposition are described and their pathophysiological pathways are compared. In addition, glymphatic system impairment is explored as a potential mutual endpoint for these pathways in the development of SANS.

Ultrasound Biomicroscopy as a Novel, Potential Modality to Evaluate Anterior Segment Ophthalmic Structures during Spaceflight: An Analysis of Current Technology.

Ocular health is currently a major concern for astronauts on current and future long-duration spaceflight missions. Spaceflight-associated neuro-ocular syndrome (SANS) is a collection of ophthalmic and neurologic findings that is one potential physiologic barrier to interplanetary spaceflight. Since its initial report in 2011, our understanding of SANS has advanced considerably, with a primary focus on posterior ocular imaging including fundus photography and optical coherence tomography. However, there may be changes to the anterior segment that have not been identified. Additional concerns to ocular health in space include corneal damage and radiation-induced cataract formation. Given these concerns, precision anterior segment imaging of the eye would be a valuable addition to future long-duration spaceflights. The purpose of this paper is to review ultrasound biomicroscopy (UBM) and its potential as a noninvasive, efficient imaging modality for spaceflight. The analysis of UBM for spaceflight is not well defined in the literature, and such technology may help to provide further insights into the overall anatomical changes in the eye in microgravity.

Ocular immunology and inflammation under microgravity conditions and the pathogenesis of spaceflight associated neuro-ocular syndrome (SANS).

Ocular immunology and inflammation under microgravity conditions and the pathogenesis of spaceflight associated neuro-ocular syndrome (SANS).

Dynamic changes in perivascular space morphology predict signs of spaceflight-associated neuro-ocular syndrome in bed rest

During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Linking cerebral hemodynamics and ocular microgravity-induced alterations through an in silico-in vivo head-down tilt framework

Head-down tilt (HDT) has been widely proposed as a terrestrial analog of microgravity and used also to investigate the occurrence of spaceflight-associated neuro-ocular syndrome (SANS), which is currently considered one of the major health risks for human spaceflight. We propose here an in vivo validated numerical framework to simulate the acute ocular-cerebrovascular response to 6° HDT, to explore the etiology and pathophysiology of SANS. The model links cerebral and ocular posture-induced hemodynamics, simulating the response of the main cerebrovascular mechanisms, as well as the relationship between intracranial and intraocular pressure to HDT. Our results from short-term (10 min) 6° HDT show increased hemodynamic pulsatility in the proximal-to-distal/capillary-venous cerebral direction, a marked decrease (-43%) in ocular translaminar pressure, and an increase (+31%) in ocular perfusion pressure, suggesting a plausible explanation of the underlying mechanisms at the onset of ocular globe deformation and edema formation over longer time scales.

Development of optic disc edema during 30 days of hypercapnic head-down tilt bed rest is associated with short sleep duration and blunted temperature amplitude.

Sleep and circadian temperature disturbances occur with spaceflight and may, in part, result from the chronically elevated carbon dioxide (CO2) levels on the international space station. Impaired sleep may contribute to decreased glymphatic clearance and, when combined with the chronic headward fluid shift during actual spaceflight or the spaceflight analog head-down tilt bed rest (HDTBR), may contribute to the development of optic disc edema. We determined if strict HDTBR combined with mildly elevated CO2 levels influenced sleep and core temperature and was associated with the development of optic disc edema. Healthy participants (5 females) aged 25-50 yr, underwent 30 days of strict 6° HDTBR with ambient Pco2 = 4 mmHg. Measures of sleep, 24-h core temperature, overnight transcutaneous CO2, and Frisén grade edema were made pre-HDTBR, on HDTBR days 4, 17, 28, and post-HDTBR days 4 and 10. During all HDTBR time points, sleep, core temperature, and overnight transcutaneous CO2 were not different than the pre-HDTBR measurements. However, independent of the HDTBR intervention, the odds ratios {mean [95% confidence interval (CI)]} for developing Frisén grade optic disc edema were statistically significant for each hour below the mean total sleep time (2.2 [1.1-4.4]) and stage 2 nonrapid eye movement (NREM) sleep (4.8 [1.3-18.6]), and above the mean for wake after sleep onset (3.6 [1.2-10.6]) and for each 0.1°C decrease in core temperature amplitude below the mean (4.0 [1.4-11.7]). These data suggest that optic disc edema occurring during HDTBR was more likely to occur in those with short sleep duration and/or blunted temperature amplitude.NEW & NOTEWORTHY We determined that sleep and 24-h core body temperature were unaltered by 30 days exposure to the spaceflight analog strict 6° head-down tilt bed rest (HDTBR) in a 0.5% CO2 environment. However, shorter sleep duration, greater wake after sleep onset, and lower core temperature amplitude present throughout the study were associated with the development of optic disc edema, a key finding of spaceflight-associated neuro-ocular syndrome.

Navigating the Unknown: A Comprehensive Review of Spaceflight-Associated Neuro-Ocular Syndrome.

Spaceflight-associated neuro-ocular syndrome (SANS) is a complex and multifaceted condition that affects astronauts during and after their missions in space. This comprehensive review delves into the various aspects of SANS, providing a thorough understanding of its definition, historical context, clinical presentation, epidemiology, diagnostic techniques, preventive measures, and management strategies. Various ocular and neurological symptoms, including visual impairment, optic disc edema, choroidal folds, retinal changes, and increased intracranial pressure, characterize SANS. While microgravity is a primary driver of SANS, other factors like radiation exposure, genetic predisposition, and environmental conditions within spacecraft contribute to its development. The duration of space missions is a significant factor, with longer missions associated with a higher incidence of SANS. This review explores the diagnostic criteria and variability in SANS presentation, shedding light on early detection and management challenges. The epidemiology section provides insights into the occurrence frequency, affected astronauts' demographics, and differences between long-term and short-term missions. Diagnostic tools, including ophthalmological assessments and imaging techniques, are crucial in monitoring astronaut health during missions. Preventive measures are vital in mitigating the impact of SANS. Current strategies, ongoing research in prevention methods, lifestyle and behavioral factors, and the potential role of artificial gravity are discussed in detail. Additionally, the review delves into interventions, potential pharmacological treatments, rehabilitation, and long-term management considerations for astronauts with SANS. The conclusion underscores the importance of continued research in SANS, addressing ongoing challenges, and highlighting unanswered questions. With the expansion of human space exploration, understanding and managing SANS is imperative to ensure the health and well-being of astronauts during long-duration missions. This review is a valuable resource for researchers, healthcare professionals, and space agencies striving to enhance our knowledge and address the complexities of SANS.

FA4SANS-GAN: A Novel Machine Learning Generative Adversarial Network to Further Understand Ophthalmic Changes in Spaceflight-Associated Neuro-Ocular Syndrome (SANS)

PurposeTo provide automated system for synthesizing fluorescein angiography (FA) images from color fundus (CF) photographs for averting risks associated with fluorescein dye and extend its future application to Space-associated neuro-ocular syndrome (SANS) detection in spaceflight where resources are limited. DesignDevelopment and validation of a novel conditional generative adversarial network (GAN) trained on limited amount of fluorescein angiography and color fundus images with diabetic retinopathy and control cases. ParticipantsColor fundus and fluorescein angiography paired images for unique patients were collected from a publicly available study. MethodsFA4SANS-GAN was trained to generate fluorescein angiography images from color fundus photographs using two multi-scale generators coupled with two patch-GAN discriminators. 850 CF and FA images were utilized for training by augmenting images from 17 unique patients. The model was evaluated on 56 fluorescein images collected from 14 unique patients. In addition, it was compared with three other GAN architectures trained on the same dataset. Furthermore, we test the robustness of the models against acquisition noise and retaining structural information when introduced to artificially created biological markers. Main Outcome MeasureFor GAN synthesis metric Fréchet Inception Distance (FID) and Kernel Inception Distance (KID). Also, two one-sided tests (TOST) based on Welch's t-test for measuring statistical significance. ResultsOn test FA images, mean FID for FA4SANS-GAN was 39.8 (SD 9.9), which is better than GANgio model’s mean of 43.2 (SD 13.7), Pix2PixHD’s mean of 57.3 (SD 11.5) and Pix2Pix’s mean of 67.5 (SD 11.7). Similarly for KID, FA4SANS-GAN achieved mean of 0.00278 (SD 0.00167) which is better than other three model’s mean KID of 0.00303 (SD 0.00216), 0.00609 (SD 0.00238), 0.00784 (SD 0.00218). For TOST measurement, FA4SANS-GAN has proven to be statistically significant vs. GANgio (p = 0.006); vs Pix2PixHD (p < 0.00001); and vs. Pix2Pix (p < 0.00001). ConclusionOur study has shown FA4SANS-GAN to be statistically significant for two GAN synthesis metrics. Moreover, it is robust against acquisition noise, and can retain clear biological markers compared to the other three GAN architectures. This deployment of this model can be crucial in International Space Station (ISS) for detecting Spaceflight-associated neuro-ocular syndrome (SANS).

Optic disc edema during strict 6° head-down tilt bed rest is related to one-carbon metabolism pathway genetics and optic cup volume

Some astronauts on International Space Station missions experience neuroophthalmological pathologies as part of spaceflight associated neuro-ocular syndrome (SANS). Strict head-down tilt bed rest (HDTBR) is a spaceflight analog that replicates SANS findings and those who had 3–4 risk alleles (G and C alleles from the methionine synthase reductase [MTRR] A66G and serine hydroxymethyltransferase [SHMT1] C1420T, respectively) as compared to 1-2 risk alleles, had a greater increase in total retinal thickness (TRT). The objective of this study was to identify factors that contribute to the individual variability of the development of SANS in a 60 d HDTBR at the German Aerospace Center’s:envihab facility, Cologne Germany. 22 of 24 subjects who participated in the HDTBR study provided blood samples for genetic analysis. Total retinal thickness and optic cup volume were measured before and after bed rest. Subjects with 3–4 versus 0-2 risk alleles had greater ΔTRT during and after bed rest, and the model improved with the addition of baseline optic cup volume. This bed rest study confirms that variants of MTRR and SHMT1 are associated with ocular pathologies. Subjects with more risk alleles had the greatest HDTBR-induced ΔTRT, reaffirming that genetics predispose some individuals to developing SANS. Preflight optic cup volume and genetics better predict ΔTRT than either one alone. Whether nutritional supplements can override the genetic influences on biochemistry, physiology, and pathophysiology remains to be tested. These findings have significant implications for both aerospace and terrestrial medicine.

Ocular rigidity and choroidal thickness changes in response to microgravity: A case study

PurposeTo evaluate ocular rigidity and choroidal thickness changes in response to microgravity and the Valsalva maneuver in a private astronaut. MethodsOphthalmological examination and Optical Coherence Tomography were performed before, during, and after space flight. Choroidal thickness was measured at all time points at rest and during the Valsalva maneuver. Ocular rigidity was obtained before and after flight using a non-invasive method enhanced with deep learning-based choroid segmentation. ResultsOcular rigidity decreased after space flight compared to baseline. There was an increase in average choroidal thickness during the Valsalva maneuver compared to the resting condition before, during, and after space flight, and such increase was greater when the Valsalva maneuver was performed during space flight. Conclusions and importanceThe data indicates biomechanical changes to ocular tissues because of space flight and greater choroidal thickness increase. The findings could lead to a better understanding of space flight-associated neuro-ocular syndrome and may have repercussions for short duration missions in a nascent industry.

Intraocular Pressure during Spaceflight and Risk of Glaucomatous Damage in Prolonged Microgravity

Microgravity introduces diverse pathological and various physiological changes to the human body, including intraocular pressure. Astronauts may develop a constellation of symptoms and signs including optic disc edema, choroidal folds, and a hyperopic shift from the flattening of the globe. These ocular findings have been collectively termed spaceflight-associated neuro-ocular syndrome (SANS). SANS is a condition that is unique to long-duration spaceflight. The precise pathogenesis of SANS remains ill-defined, but several hypotheses have been proposed that may be influenced by intraocular pressure. Countermeasures for SANS research also include techniques that impact intraocular pressure. In this article, we discuss intraocular pressure during spaceflight, the translaminar pressure gradient, SANS and potential SANS countermeasures, and the potential for glaucomatous damage during spaceflight.

Precisional modulation of translaminar pressure gradients for ophthalmic diseases.

The translaminar pressure gradient (TLPG) refers to two forces at the lamina cribosa of the optic nerve: the anteriorly acting intracranial pressure (ICP), and posteriorly-acting intraocular pressure (IOP). It has been proposed that controlling the translaminar pressure gradient at regular intervals may preserve the optic nerve and slow the course of glaucoma. The precisional modulation of this TLPG is a recently introduced concept that may play a role in the treatment of ophthalmic diseases such as glaucoma. In this manuscript, we review the applications of pressurized goggles on ophthalmic diseases. We also elaborate upon current investigations in modulation of the TLPG including goggles and the multi-pressure dial goggle. We discuss future research directions for ophthalmic diseases including spaceflight associated neuro-ocular syndrome (SANS), a large physiological barrier to future long-duration spaceflight.

The spaceflight contrast sensitivity hypothesis and its role to investigate the pathophysiology of spaceflight-associated neuro-ocular syndrome

The spaceflight contrast sensitivity hypothesis and its role to investigate the pathophysiology of spaceflight-associated neuro-ocular syndrome

Poster Session: Detecting spaceflight associated neuro-ocular syndrome (SANS) using light-weight convolutional neural networks.

Spaceflight-associated neuro-ocular syndrome (SANS) is a collection of neuro-ophthalmic findings that occurs in astronauts as a result of prolonged microgravity exposure in space. Due to limited resources on board long-term spaceflight missions, early disease diagnosis and prognosis of SANS become unviable. Moreover, the current retinal imaging techniques onboard the international space station (ISS), such as optical coherence tomography (OCT), ultrasound imaging, and fundus photography, require an expert to distinguish between SANS and similar ophthalmic diseases. With the advent of Deep Learning, diagnosing diseases (such as diabetic retinopathy) from structural retinal images are being automated. In this study, we propose a lightweight convolutional neural network incorporating an EfficientNet encoder for detecting SANS from OCT images. We used 6303 OCT B-scan images for training/validation (80%/20% split) and 945 for testing. Our model achieved 84.2% accuracy on the test set, i.e., 85.6% specificity, and 82.8% sensitivity. Moreover, it outperforms two other state-of-the-art pre-trained architectures, ResNet50-v2 and MobileNet-v2, by 21.4% and 13.1%. Additionally, we use GRAD-CAM to visualize activation maps of intermediate layers to test the interpretability of our model's prediction. The proposed architecture enables fast and efficient prediction of SANS-like conditions for future long-term spaceflight mission in which computational and clinical resources are limited.

Insights into spaceflight-associated neuro-ocular syndrome with review of intraocular and orbital findings.

Spaceflight-associated neuro-ocular syndrome (SANS) remains a phenomenological term, and advances in ophthalmic imaging as well as new insights from ground-based experiments have given support to new theories of how SANS develops and what may be done to counter it. SANS has been postulated to arise from elevated intracranial pressure (ICP) during long-duration spaceflight (LDSF). However, recent work has shown that acute microgravity exposure does not increase ICP, and the effect of cephalad fluid shifts on ICP in microgravity remain unknown. In addition, structural imaging of the retina and optic nerve show changes after LDSF that are distinct from findings in terrestrial patients with elevated ICP. Since astronauts have not reported symptoms that would be expected with chronic ICP elevation, new theories that orbital and/or intracranial venous pressure may be the primary contributors to the development of SANS. Research has been filling knowledge gaps that exist regarding the cause(s) of SANS, and these advances are crucial steps in the effort to design countermeasures that will be required before human deep space exploration missions can be undertaken.

Anemia and Spaceflight Associated Neuro-Ocular Syndrome (SANS).

Spaceflight associated neuro-ocular syndrome (SANS) is a collection of distinct findings seen in some astronauts following prolonged spaceflight and is characterized by: optic disc edema, globe flattening, and choroidal folds. In this manuscript, we describe the potential mechanisms linking anemia and SANS. Future research aimed at understanding the relationship between these conditions may help to develop countermeasures and mitigation efforts for SANS.

Artificial Intelligence Frameworks to Detect and Investigate the Pathophysiology of Spaceflight Associated Neuro-Ocular Syndrome (SANS).

Spaceflight associated neuro-ocular syndrome (SANS) is a unique phenomenon that has been observed in astronauts who have undergone long-duration spaceflight (LDSF). The syndrome is characterized by distinct imaging and clinical findings including optic disc edema, hyperopic refractive shift, posterior globe flattening, and choroidal folds. SANS serves a large barrier to planetary spaceflight such as a mission to Mars and has been noted by the National Aeronautics and Space Administration (NASA) as a high risk based on its likelihood to occur and its severity to human health and mission performance. While it is a large barrier to future spaceflight, the underlying etiology of SANS is not well understood. Current ophthalmic imaging onboard the International Space Station (ISS) has provided further insights into SANS. However, the spaceflight environment presents with unique challenges and limitations to further understand this microgravity-induced phenomenon. The advent of artificial intelligence (AI) has revolutionized the field of imaging in ophthalmology, particularly in detection and monitoring. In this manuscript, we describe the current hypothesized pathophysiology of SANS and the medical diagnostic limitations during spaceflight to further understand its pathogenesis. We then introduce and describe various AI frameworks that can be applied to ophthalmic imaging onboard the ISS to further understand SANS including supervised/unsupervised learning, generative adversarial networks, and transfer learning. We conclude by describing current research in this area to further understand SANS with the goal of enabling deeper insights into SANS and safer spaceflight for future missions.

Increased hemodynamic pulsatility in the cerebral microcirculation during parabolic flight-induced microgravity: A computational investigation

Ground-based spaceflight analogs play a crucial role to understand and predict cardiovascular alterations during microgravity in a controlled and affordable way. Despite their extensive use in recent years, cerebral hemodynamics in microgravity remains poorly understood, multifaceted, and definitive data are still missing, due to the limited number and different duration of experiments, the individual variability, and the intrinsic difficulty in obtaining direct clinical measures. However, there is growing evidence that hemodynamic changes are among the underlying causes of neurological dysfunctions, such as the Spaceflight Associated Neuro-ocular Syndrome (SANS). We proposed to investigate the cerebral hemodynamics during supine posture parabolic flight by means of a validated computational approach, combining a 0D-1D central-systemic cardiovascular model together with a 0D cerebrovascular model. Present findings showed that, although with over- and under-shoots in the transition from one gravitational environment to the other, beat-averaged pressure and flow rate steady state values did not greatly vary between 0g and 1g due to the cerebral autoregulation. On the contrary, in microgravity there was an augmented hemodynamic pulsatility which increased towards the deep cerebral microcirculation. The greater pulsatility, inducing a higher variability of maximum and minimum values reached within each beat, was here observed for the first time also for important cerebral markers, such as the intracranial pressure, the cerebrospinal fluid circulation, and the cerebral blood flow. The proposed approach offers novel insights on how hemodynamic alterations, such as cerebral hypoperfusions and intracranial pressure fluctuations, can contribute to explain neurovestibular dysfunctions emerging during short-term exposure to 0g, including the onset of nausea, SANS and cognitive fatigue.