Cerebrovascular Effects of Lower Body Negative Pressure at 3T MRI: Implications for Long-Duration Space Travel.

BACKGROUND: Optic disc edema develops in most astronauts during long-duration spaceflight. It is hypothesized to result from weightlessness-induced venous congestion of the head and neck and is an unresolved health risk of space travel. PURPOSE: Determine if short-term application of lower body negative pressure (LBNP) could reduce internal jugular vein (IJV) expansion associated with the supine posture without negatively impacting cerebral perfusion or causing IJV flow stasis. STUDY TYPE: Prospective. SUBJECTS: Nine healthy volunteers (six women). FIELD STRENGTH/SEQUENCE: 3T/cine two-dimensional phase-contrast gradient echo; pseudo-continuous arterial spin labeling single-shot gradient echo echo-planar. ASSESSMENT: The study was performed with two sequential conditions in randomized order: supine posture and supine posture with 25 mmHg LBNP (LBNP25 ). LBNP was achieved by enclosing the lower extremities in a semi-airtight acrylic chamber connected to a vacuum. Heart rate, bulk cerebrovasculature flow, IJV cross-sectional area, fractional IJV outflow relative to arterial inflow, and cerebral perfusion were assessed in each condition. STATISTICAL TESTS: Paired t-tests were used to compare measurement means across conditions. Significance was defined as P < 0.05. RESULTS: LBNP25 significantly increased heart rate from 64 ± 9 to 71 ± 8 beats per minute and significantly decreased IJV cross-sectional area, IJV outflow fraction, cerebral arterial flow rate, and cerebral arterial stroke volume from 1.28 ± 0.64 to 0.56 ± 0.31 cm2 , 0.75 ± 0.20 to 0.66 ± 0.28, 780 ± 154 to 708 ± 137 mL/min and 12.2 ± 2.8 to 9.7 ± 1.7 mL/cycle, respectively. During LBNP25 , there was no significant change in gray or white matter cerebral perfusion (P = 0.26 and P = 0.24 respectively) and IJV absolute mean peak flow velocity remained ≥4 cm/sec in all subjects. DATA CONCLUSION: Short-term application of LBNP25 reduced IJV expansion without decreasing cerebral perfusion or inducing IJV flow stasis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Surveillance for jugular venous thrombosis in astronauts.

BACKGROUND: Thrombosis of the left internal jugular vein in an astronaut aboard the International Space Station was recently described, incidentally discovered during a research study of blood flow in neck veins in microgravity. Given this event, and the high incidence of flow abnormalities, the National Aeronautics and Space Administration (NASA) instituted an occupational surveillance program to evaluate astronauts for venous thrombosis. METHODS: Duplex ultrasound of the bilateral internal jugular veins was conducted on all NASA astronauts terrestrially, and at three points during spaceflight. Respiratory maneuvers were performed. Images were analyzed for thrombosis and certain hemodynamic characteristics, including peak velocity and degree of echogenicity. RESULTS: Eleven astronauts were evaluated with matching terrestrial and in-flight ultrasounds. No thrombosis was detected. Compared to terrestrial ultrasound measurements, in-flight peak velocity was reduced and lowest in the left. Six of 11 astronauts had mild-moderate echogenicity in the left internal jugular vein during spaceflight, but none had more than mild echogenicity in the right internal jugular vein. Two astronauts developed retrograde blood flow in the left internal jugular vein. CONCLUSION: Abnormal flow characteristics in microgravity, most prominent in the left internal jugular vein, may signal an increased risk for thrombus formation in some individuals.

Intracranial Effects of Microgravity: A Prospective Longitudinal MRI Study.

Background Astronauts on long-duration spaceflight missions may develop changes in ocular structure and function, which can persist for years after the return to normal gravity. Chronic exposure to elevated intracranial pressure during spaceflight is hypothesized to be a contributing factor, however, the etiologic causes remain unknown. Purpose To investigate the intracranial effects of microgravity by measuring combined changes in intracranial volumetric parameters, pituitary morphologic structure, and aqueductal cerebrospinal fluid (CSF) hydrodynamics relative to spaceflight and to establish a comprehensive model of recovery after return to Earth. Materials and Methods This prospective longitudinal MRI study enrolled astronauts with planned long-duration spaceflight. Measures were conducted before spaceflight followed by 1, 30, 90, 180, and 360 days after landing. Intracranial volumetry and aqueductal CSF hydrodynamics (CSF peak-to-peak velocity amplitude and aqueductal stroke volume) were quantified for each phase. Qualitative and quantitative changes in pre- to postflight (day 1) pituitary morphologic structure were determined. Statistical analysis included separate mixed-effects models per dependent variable with repeated observations over time. Results Eleven astronauts (mean age, 45 years ± 5 [standard deviation]; 10 men) showed increased mean volumes in the brain (28 mL; P < .001), white matter (26 mL; P < .001), mean lateral ventricles (2.2 mL; P < .001), and mean summated brain and CSF (33 mL; P < .001) at postflight day 1 with corresponding increases in mean aqueductal stroke volume (14.6 µL; P = .045) and mean CSF peak-to-peak velocity magnitude (2.2 cm/sec; P = .01). Summated mean brain and CSF volumes remained increased at 360 days after spaceflight (28 mL; P < .001). Qualitatively, six of 11 (55%) astronauts developed or showed exacerbated pituitary dome depression compared with baseline. Average midline pituitary height decreased from 5.9 to 5.3 mm (P < .001). Conclusion Long-duration spaceflight was associated with increased pituitary deformation, augmented aqueductal cerebrospinal fluid (CSF) hydrodynamics, and expansion of summated brain and CSF volumes. Summated brain and CSF volumetric expansion persisted up to 1 year into recovery, suggesting permanent alteration. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Lev in this issue.

Jugular venous flow dynamics during acute weightlessness.

During spaceflight, fluids shift headward, causing internal jugular vein (IJV) distension and altered hemodynamics, including stasis and retrograde flow, that may increase the risk of thrombosis. This study's purpose was to determine the effects of acute exposure to weightlessness (0-G) on IJV dimensions and flow dynamics. We used two-dimensional (2-D) ultrasound to measure IJV cross-sectional area (CSA) and Doppler ultrasound to characterize venous blood flow patterns in the right and left IJV in 13 healthy participants (6 females) while 1) seated and supine on the ground, 2) supine during 0-G parabolic flight, and 3) supine during level flight (at 1-G). On Earth, in 1-G, moving from seated to supine posture increased CSA in both left (+62 [95% CI: +42 to 81] mm2, P < 0.0001) and right (+86 [95% CI: +58 to 113] mm2, P < 0.00012) IJV. Entry into 0-G further increased IJV CSA in both left (+27 [95% CI: +5 to 48] mm2, P = 0.02) and right (+30 [95% CI: +0.3 to 61] mm2, P = 0.02) relative to supine in 1-G. We observed stagnant flow in the left IJV of one participant during 0-G parabolic flight that remained during level flight but was not present during any imaging during preflight measures in the seated or supine postures; normal venous flow patterns were observed in the right IJV during all conditions in all participants. Alterations to cerebral outflow dynamics in the left IJV can occur during acute exposure to weightlessness and thus, may increase the risk of venous thrombosis during any duration of spaceflight.NEW & NOTEWORTHY The absence of hydrostatic pressure gradients in the vascular system and loss of tissue weight during weightlessness results in altered flow dynamics in the left internal jugular vein in some astronauts that may contribute to an increased risk of thromboembolism during spaceflight. Here, we report that the internal jugular veins distend bilaterally in healthy participants and that flow stasis can occur in the left internal jugular vein during acute weightlessness produced by parabolic flight.

Uneven terrain affects metabolic cost and gait in simulated complex lunar surfaces.

Objective. Upcoming missions of the National Aeronautics and Space Administration (NASA) to the Moon will include extensive human exploration of the lunar surface. Walking will be essential for many exploration tasks, and metabolic cost during ambulation on simulated complex lunar surfaces requires further characterization. In this study, ten healthy subjects (6 male and 4 female) participated in three simulated lunar terrain walking conditions at the NASA Johnson Space Center's planetary 'Rock Yard': (1) flat terrain, (2) flat terrain with obstacles, and (3) mixed terrain.Approach.Energy expenditure and gait were quantified with a wearable metabolic energy expenditure monitoring system and body-worn inertial measurement units (IMUs), respectively.Main results.It was found that participants walking on the mixed terrain, representing the highest workload condition, required significantly higher metabolic costs than in other terrain conditions (p< 0.001). Additionally, our novel IMU-based gait variables discriminated different terrains and identified changes in gait in simulated lunar terrain environments.Significance.Our results showed that the various surface irregularities and inconsistencies could cause additional physical effort while walking on the complex terrain. These findings provide insight into the effects of terrain on metabolic energy expenditure during simulated lunar extravehicular activities.

External to internal cranial perfusion shifts during simulated weightlessness: Results from a randomized cross-over trial.

The exact pathophysiology of the spaceflight-associated neuro-ocular syndrome (SANS) has so far not been completely elucidated. In this study we assessed the effect of acute head-down tilt position on the mean flow of the intra- and extracranial vessels. Our results suggest a shift from the external to the internal system that might play an important role in the pathomechanism of SANS.

MRI-based quantification of posterior ocular globe flattening during 60 days of strict 6° head-down tilt bed rest with and without daily centrifugation.

Spaceflight associated neuro-ocular syndrome (SANS) is associated with acquired optic disc edema, hyperopia, and posterior globe flattening in some astronauts during long-duration spaceflight possibly due to the headward fluid redistribution in microgravity. The goal of this study was to assess whether strict head-down tilt (HDT) bed rest as a spaceflight analog would produce globe flattening and whether centrifugation could prevent these changes. Twenty-four healthy subjects separated into three groups underwent 60 days of strict 6° HDT bed rest: one control group with no countermeasure (n = 8) and two countermeasure groups exposed to 30 min daily of short-arm centrifugation as a means of artificial gravity (AG), either intermittent (iAG, n = 8) or continuous (cAG, n = 8). Magnetic resonance images (MRI) were collected at baseline, HDT-day 14, HDT-day 52, and 3 days after bed rest. An automated method was applied to quantify posterior globe volume displacement compared with baseline scans. On average, subjects showed an increasing degree of globe volume displacement with bed rest duration (means ± SE: 1.41 ± 1.01 mm3 on HDT14 and 4.04 ± 1.19 mm3 on HDT52) that persisted post-bed rest (5.51 ± 1.26 mm3). Application of 30 min daily AG did not have a significant impact on globe volume displacement (P = 0.42 for cAG and P = 0.93 for iAG compared with control). These results indicate that strict 6° HDT bed rest produced displacement of the posterior globe with a trend of increasing displacement with longer duration that was not prevented by daily 30 min exposure to AG.NEW & NOTEWORTHY Head-down tilt (HDT) bed rest is commonly used as a spaceflight analog for investigating spaceflight associated neuro-ocular syndrome (SANS). Posterior ocular globe flattening has been identified in astronauts with SANS but until now has not been investigated during HDT bed rest. In this study, posterior ocular globe volume displacement was quantified before, during, and after HDT bed rest and countermeasures were tested for their potential to reduce the degree of globe flattening.

Noninvasive indicators of intracranial pressure before, during, and after long-duration spaceflight.

Weightlessness induces a cephalad shift of blood and cerebrospinal fluid that may increase intracranial pressure (ICP) during spaceflight, whereas lower body negative pressure (LBNP) may provide an opportunity to caudally redistribute fluids and lower ICP. To investigate the effects of spaceflight and LBNP on noninvasive indicators of ICP (nICP), we studied 13 crewmembers before and after spaceflight in seated, supine, and 15° head-down tilt postures, and at ∼45 and ∼150 days of spaceflight with and without 25 mmHg LBNP. We used four techniques to quantify nICP: cerebral and cochlear fluid pressure (CCFP), otoacoustic emissions (OAE), ultrasound measures of optic nerve sheath diameter (ONSD), and ultrasound-based internal jugular vein pressure (IJVp). On flight day 45, two nICP measures were lower than preflight supine posture [CCFP: mean difference -98.5 -nL (CI: -190.8 to -6.1 -nL), P = 0.037]; [OAE: -19.7° (CI: -10.4° to -29.1°), P < 0.001], but not significantly different from preflight seated measures. Conversely, ONSD was not different than any preflight posture, whereas IJVp was significantly greater than preflight seated measures [14.3 mmHg (CI: 10.1 to 18.5 mmHg), P < 0.001], but not significantly different than preflight supine measures. During spaceflight, acute LBNP application did not cause a significant change in nICP indicators. These data suggest that during spaceflight, nICP is not elevated above values observed in the seated posture on Earth. Invasive measures would be needed to provide absolute ICP values and more precise indications of ICP change during various phases of spaceflight.NEW & NOTEWORTHY The current study provides new evidence that intracranial pressure (ICP), as assessed with noninvasive measures, may not be elevated during long-duration spaceflight. In addition, the acute use of lower body negative pressure did not significantly reduce indicators of ICP during weightlessness.

Optic disc edema and chorioretinal folds develop during strict 6° head-down tilt bed rest with or without artificial gravity.

Spaceflight associated neuro-ocular syndrome (SANS) is hypothesized to develop as a consequence of the chronic headward fluid shift that occurs in sustained weightlessness. We exposed healthy subjects (n = 24) to strict 6° head-down tilt bed rest (HDTBR), an analog of weightlessness that generates a sustained headward fluid shift, and we monitored for ocular changes similar to findings that develop in SANS. Two-thirds of the subjects received a daily 30-min exposure to artificial gravity (AG, 1 g at center of mass, ~0.3 g at eye level) during HDTBR by either continuous (cAG, n = 8) or intermittent (iAG, n = 8) short-arm centrifugation to investigate whether this intervention would attenuate headward fluid shift-induced ocular changes. Optical coherence tomography images were acquired to quantify changes in peripapillary total retinal thickness (TRT), retinal nerve fiber layer thickness, and choroidal thickness, and to detect chorioretinal folds. Intraocular pressure (IOP), optical biometry, and standard automated perimetry data were collected. TRT increased by 35.9 µm (95% CI, 19.9-51.9 µm, p < 0.0001), 36.5 µm (95% CI, 4.7-68.2 µm, p = 0.01), and 27.6 µm (95% CI, 8.8-46.3 µm, p = 0.0005) at HDTBR day 58 in the control, cAG, and iAG groups, respectively. Chorioretinal folds developed in six subjects across the groups, despite small increases in IOP. Visual function outcomes did not change. These findings validate strict HDTBR without elevated ambient CO2 as a model for investigating SANS and suggest that a fluid shift reversal of longer duration and/or greater magnitude at the eye may be required to prevent or mitigate SANS.

Automated MRI-based quantification of posterior ocular globe flattening and recovery after long-duration spaceflight.

BACKGROUND/OBJECTIVES: Spaceflight associated neuro-ocular syndrome (SANS), a health risk related to long-duration spaceflight, is hypothesized to result from a headward fluid shift that occurs with the loss of hydrostatic pressure gradients in weightlessness. Shifts in the vascular and cerebrospinal fluid compartments alter the mechanical forces at the posterior eye and lead to flattening of the posterior ocular globe. The goal of the present study was to develop a method to quantify globe flattening observed by magnetic resonance imaging after spaceflight. SUBJECTS/METHODS: Volumetric displacement of the posterior globe was quantified in 10 astronauts at 5 time points after spaceflight missions of ~6 months. RESULTS: Mean globe volumetric displacement was 9.88 mm3 (95% CI 4.56-15.19 mm3, p < 0.001) on the first day of assessment after the mission (R[return]+ 1 day); 9.00 mm3 (95% CI 3.73-14.27 mm3, p = 0.001) at R + 30 days; 6.53 mm3 (95% CI 1.24-11.83 mm3, p < 0.05) at R + 90 days; 4.45 mm3 (95% CI -0.96 to 9.86 mm3, p = 0.12) at R + 180 days; and 7.21 mm3 (95% CI 1.82-12.60 mm3, p < 0.01) at R + 360 days. CONCLUSIONS: There was a consistent inward displacement of the globe at the optic nerve, which had only partially resolved 1 year after landing. More pronounced globe flattening has been observed in previous studies of astronauts; however, those observations lacked quantitative measures and were subjective in nature. The novel automated method described here allows for detailed quantification of structural changes in the posterior globe that may lead to an improved understanding of SANS.

Intraocular pressure and choroidal thickness respond differently to lower body negative pressure during spaceflight.

Spaceflight-associated neuro-ocular syndrome (SANS) develops during long-duration (>1 mo) spaceflight presumably because of chronic exposure to a headward fluid shift that occurs in weightlessness. We aimed to determine whether reversing this headward fluid shift with acute application of lower body negative pressure (LBNP) can influence outcome measures at the eye. Intraocular pressure (IOP) and subfoveal choroidal thickness were therefore evaluated by tonometry and optical coherence tomography (OCT), respectively, in 14 International Space Station crewmembers before flight in the seated, supine, and 15° head-down tilt (HDT) postures and during spaceflight, without and with application of 25 mmHg LBNP. IOP in the preflight seated posture was 14.4 mmHg (95% CI, 13.5-15.2 mmHg), and spaceflight elevated this value by 1.3 mmHg (95% CI, 0.7-1.8 mmHg, P < 0.001). Acute exposure to LBNP during spaceflight reduced IOP to 14.2 mmHg (95% CI, 13.4-15.0 mmHg), which was equivalent to that of the seated posture (P > 0.99), indicating that venous fluid redistribution by LBNP can influence ocular outcome variables during spaceflight. Choroidal thickness during spaceflight (374 µm, 95% CI, 325-423 µm) increased by 35 µm (95% CI, 25-45 µm, P < 0.001), compared with the preflight seated posture (339 µm, 95% CI, 289-388 µm). Acute use of LBNP during spaceflight did not affect choroidal thickness (381 µm, 95% CI, 331-430 µm, P = 0.99). The finding that transmission of reduced venous pressure by LBNP did not decrease choroidal thickness suggests that engorgement of this tissue during spaceflight may reflect changes that are secondary to the chronic cerebral venous congestion associated with spaceflight.NEW & NOTEWORTHY Spaceflight induces a chronic headward fluid shift that is believed to underlie ocular changes observed in astronauts. The present study demonstrates, for the first time, that reversing this headward fluid shift via application of lower body negative pressure (LBNP) during spaceflight may alter the ocular venous system, as evidenced by a decrease in intraocular pressure. This finding indicates that LBNP has the potential to be an effective countermeasure against the headward fluid shift during spaceflight, which may then be beneficial in preventing or reversing associated ocular changes.

Mechanical countermeasures to headward fluid shifts.

Head-to-foot gravitationally induced hydrostatic pressure gradients in the upright posture on Earth are absent in weightlessness. This results in a relative headward fluid shift in the vascular and cerebrospinal fluid compartments and may underlie multiple physiological consequences of spaceflight, including the spaceflight-associated neuro-ocular syndrome. Here, we tested three mechanical countermeasures [lower body negative pressure (LBNP), venoconstrictive thigh cuffs (VTC), and impedance threshold device (ITD) resistive inspiratory breathing] individually and in combination to reduce a posture-induced headward fluid shift as a ground-based spaceflight analog. Ten healthy subjects (5 male) underwent baseline measures (seated and supine postures) followed by countermeasure exposure in the supine posture. Noninvasive measurements included ultrasound [internal jugular veins (IJV) cross-sectional area, cardiac stroke volume, optic nerve sheath diameter, noninvasive IJV pressure], transient evoked otoacoustic emissions (OAE; intracranial pressure index), intraocular pressure, choroidal thickness from optical coherence tomography imaging, and brachial blood pressure. Compared with the supine posture, IJV area decreased 48% with application of LBNP [mean ratio: 0.52, 95% confidence interval (CI): 0.44-0.60, P < 0.001], 31% with VTC (mean ratio: 0.69, 95% CI: 0.55-0.87, P < 0.001), and 56% with ITD (mean ratio: 0.44, 95% CI: 0.12-1.70, P = 0.46), measured at end-inspiration. LBNP was the only individual countermeasure to decrease the OAE phase angle (Δ -12.9 degrees, 95% CI: -25 to -0.9, P = 0.027), and use of combined countermeasures did not result in greater effects. Thus, LBNP, and to a lesser extent VTC and ITD, represents promising headward fluid shift countermeasures but will require future testing in analog and spaceflight environments.NEW & NOTEWORTHY As a weightlessness-induced headward fluid shift is hypothesized to be a primary factor underlying several physiological consequences of spaceflight, countermeasures aimed at reversing the fluid shift will likely be crucial during exploration-class spaceflight missions. Here, we tested three mechanical countermeasures individually and in various combinations to reduce a posture-induced headward fluid shift as a ground-based spaceflight analog.

Association of Structural Changes in the Brain and Retina After Long-Duration Spaceflight.

IMPORTANCE: Long-duration spaceflight induces structural changes in the brain and eye. Identification of an association between cerebral and ocular changes could help determine if there are common or independent causes and inform targeted prevention strategies or treatments. OBJECTIVE: To determine if there is an association between quantitative changes in intracranial compartment volumes and peripapillary total retinal thickness after spaceflight. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included healthy International Space Station crew members before and immediately after long-duration spaceflight. Data on race were not collected. Analysis was conducted from September to November 2020. EXPOSURES: Long-duration spaceflight (mean [SD], 191 [55] days). MAIN OUTCOMES AND MEASURES: Optical coherence tomography-derived peripapillary total retinal thickness as a quantitative assessment and early sign of optic disc edema and magnetic resonance imaging-derived measures of lateral ventricle volume, white matter volume, and whole brain plus cerebrospinal fluid volume. RESULTS: In 19 healthy crew members included in this study (5 women [26.3%], 14 men [73.7%]; mean [SD] age, 45.2 [6.4] years), analyses revealed a positive, although not definitive, association between spaceflight-induced changes in total retinal thickness and lateral ventricle volume (4.7-µm increase in postflight total retinal thickness [95% CI, -1.5 to 10.8 µm; P = .13] per 1-mL postflight increase in lateral ventricle volume). Adjustments for mission duration improved the strength of association (5.1 µm; 95% CI, -0.4 to 10.5 µm; P = .07). No associations were detected between spaceflight-induced changes in total retinal thickness and white matter volume (0.02 µm; 95% CI, -0.5 to 0.5 µm; P = .94) or brain tissue plus cerebrospinal fluid volume, an estimate of intracranial volume (0.02 µm; 95% CI, -0.6 to 0.6 µm; P = .95). CONCLUSIONS AND RELEVANCE: These results help characterize spaceflight-associated neuro-ocular syndrome and the physiologic associations of headward fluid shifts with outcomes during spaceflight on the central nervous system. The possibly weak association between increased total retinal thickness and lateral ventricle volume suggest that while weightlessness-induced fluid redistribution during spaceflight may be a common stressor to the brain and retina, the development of optic disc edema appears to be uncoupled with changes occurring in the intracranial compartment.

Quantitative magnetic resonance image assessment of the optic nerve and surrounding sheath after spaceflight.

A subset of long-duration spaceflight astronauts have experienced ophthalmic abnormalities, collectively termed spaceflight-associated neuro-ocular syndrome (SANS). Little is understood about the pathophysiology of SANS; however, microgravity-induced alterations in intracranial pressure (ICP) due to headward fluid shifts is the primary hypothesized contributor. In particular, potential changes in optic nerve (ON) tortuosity and ON sheath (ONS) distension may indicate altered cerebrospinal fluid dynamics during weightlessness. The present longitudinal study aims to provide a quantitative analysis of ON and ONS cross-sectional areas, and ON deviation, an indication of tortuosity, before and after spaceflight. Ten astronauts undergoing ~6-month missions on the International Space Station (ISS) underwent high-resolution magnetic resonance imaging (MRI) preflight and at five recovery time points extending to 1 year after return from the ISS. The mean changes in ON deviation, ON cross-sectional area, and ONS cross-sectional area immediately post flight were -0.14 mm (95% CI: -0.36 to 0.08, Bonferroni-adjusted P = 1.00), 0.13 mm2 (95% CI -0.66 to 0.91, Bonferroni-adjusted P = 1.00), and -0.22 mm2 (95% CI: -1.78 to 1.34, Bonferroni-adjusted P = 1.00), respectively, and remained consistent during the recovery period. Terrestrially, ONS distension is associated with increased ICP; therefore, these results suggest that, on average, ICP was not pathologically elevated immediately after spaceflight. However, a subject diagnosed with optic disc edema (Frisen Grade 1, right eye) displayed increased ONS area post flight, although this increase is relatively small compared to clinical populations with increased ICP. Advanced quantitative MRI-based assessment of the ON and ONS could help our understanding of SANS and the role of ICP.

Brain Physiological Response and Adaptation During Spaceflight.

More than half of astronauts returning from long-duration missions on the International Space Station present with neuro-ocular structural and/or functional changes, including optic disc edema, optic nerve sheath distension, globe flattening, choroidal folds, or hyperopic shifts. This spaceflight-associated neuro-ocular syndrome (SANS) represents a major risk to future exploration class human spaceflight missions, including Mars missions. Although the exact pathophysiology of SANS is unknown, evidence thus far suggests that an increase in intracranial pressure (ICP) relative to the upright position on Earth, which is due to the loss of hydrostatic pressure gradients in space, may play a leading role. This review focuses on brain physiology in the spaceflight environment, specifically on how spaceflight may affect ICP and related indicators of cranial compliance, potential factors related to the development of SANS, and findings from spaceflight as well as ground-based spaceflight analog research studies.

Assessment of Jugular Venous Blood Flow Stasis and Thrombosis During Spaceflight.

Importance: Exposure to a weightless environment during spaceflight results in a chronic headward blood and tissue fluid shift compared with the upright posture on Earth, with unknown consequences to cerebral venous outflow. Objectives: To assess internal jugular vein (IJV) flow and morphology during spaceflight and to investigate if lower body negative pressure is associated with reversing the headward fluid shift experienced during spaceflight. Design, Setting, and Participants: This prospective cohort study included 11 International Space Station crew members participating in long-duration spaceflight missions . Internal jugular vein measurements from before launch and approximately 40 days after landing were acquired in 3 positions: seated, supine, and 15° head-down tilt. In-flight IJV measurements were acquired at approximately 50 days and 150 days into spaceflight during normal spaceflight conditions as well as during use of lower body negative pressure. Data were analyzed in June 2019. Exposures: Posture changes on Earth, spaceflight, and lower body negative pressure. Main Outcomes and Measures: Ultrasonographic assessments of IJV cross-sectional area, pressure, blood flow, and thrombus formation. Results: The 11 healthy crew members included in the study (mean [SD] age, 46.9 [6.3] years, 9 [82%] men) spent a mean (SD) of 210 (76) days in space. Mean IJV area increased from 9.8 (95% CI, -1.2 to 20.7) mm2 in the preflight seated position to 70.3 (95% CI, 59.3-81.2) mm2 during spaceflight (P < .001). Mean IJV pressure increased from the preflight seated position measurement of 5.1 (95% CI, 2.5-7.8) mm Hg to 21.1 (95% CI, 18.5-23.7) mm Hg during spaceflight (P < .001). Furthermore, stagnant or reverse flow in the IJV was observed in 6 crew members (55%) on approximate flight day 50. Notably, 1 crew member was found to have an occlusive IJV thrombus, and a potential partial IJV thrombus was identified in another crew member retrospectively. Lower body negative pressure was associated with improved blood flow in 10 of 17 sessions (59%) during spaceflight. Conclusions and Relevance: This cohort study found stagnant and retrograde blood flow associated with spaceflight in the IJVs of astronauts and IJV thrombosis in at least 1 astronaut, a newly discovered risk associated with spaceflight. Lower body negative pressure may be a promising countermeasure to enhance venous blood flow in the upper body during spaceflight.

Internal Jugular Vein Volume During Head-Down Tilt and Carbon Dioxide Exposure in the SPACECOT Study.

BACKGROUND: Cerebral hemodynamics and venous outflow from the brain may be altered during exposure to microgravity or head-down tilt (HDT), an analog of microgravity, as well as by increased ambient CO2 exposure as experienced on the International Space Station. METHODS: Six healthy subjects underwent baseline tilt table testing at 0°, 6°, 12°, 18°, 24°, and 30° HDT. The right internal jugular (IJ) vein cross-sectional area (CSA) was measured at four intervals from the submandibular to the clavicular level and IJ volume was calculated. Further measurements of the IJ vein were made after ∼26 h of 12° HDT bed rest with either ambient air or 0.5% CO2 exposure, and plasma and blood volume were assessed after 4 h, 24 h, and 28.5 h HDT. RESULTS: IJ vein CSA and volume increased with progressively steeper HDT angles during baseline tilt table testing, with more prominent filling of the IJ vein at levels closer to the clavicle. Exposure to 26 h of 12° HDT bed rest with or without increased CO2, however, had little additional effect on the IJ vein. Further, bed rest resulted in a decrease in plasma volume and blood volume, although changes did not depend on atmospheric conditioning or correlate directly with changes in IJ vein CSA or volume. DISCUSSION: The hydrostatic effects of HDT can be clearly determined through measurement of the IJ vein CSA and volume; however, IJ vein dimensions may not be a reliable indicator of systemic fluid status during bed rest.Marshall-Goebel K, Stevens B, Rao CV, Suarez JI, Calvillo E, Arbeille P, Sangi-Haghpeykar H, Donoviel DB, Mulder E, Bershad EM, the SPACECOT Investigators Group. Internal jugular vein volume during head-down tilt and carbon dioxide exposure in the SPACECOT Study. Aerosp Med Hum Perform. 2018; 89(4):351-356.

Lower body negative pressure reduces optic nerve sheath diameter during head-down tilt.

The microgravity ocular syndrome (MOS) results in significant structural and functional ophthalmic changes during 6-mo spaceflight missions consistent with an increase in cerebrospinal fluid (CSF) pressure compared with the preflight upright position. A ground-based study was performed to assess two of the major hypothesized contributors to MOS, headward fluid shifting and increased ambient CO2, on intracranial and periorbital CSF. In addition, lower body negative pressure (LBNP) was assessed as a countermeasure to headward fluid shifting. Nine healthy male subjects participated in a crossover design study with five head-down tilt (HDT) conditions: -6, -12, and -18° HDT, -12° HDT with -20 mmHg LBNP, and -12° HDT with a 1% CO2 environment, each for 5 h total. A three-dimensional volumetric scan of the cranium and transverse slices of the orbita were collected with MRI, and intracranial CSF volume and optic nerve sheath diameter (ONSD) were measured after 4.5 h HDT. ONSD increased during -6° (P < 0.001), -12° (P < 0.001), and -18° HDT (P < 0.001) and intracranial CSF increased during -12° HDT (P = 0.01) compared with supine baseline. Notably, LBNP was able to reduce the increases in ONSD and intracranial CSF during HDT. The addition of 1% CO2 during HDT, however, had no further effect on ONSD, but rather ONSD increased from baseline in a similar magnitude to -12° HDT with ambient air (P = 0.001). These findings demonstrate the ability of LBNP, a technique that targets fluid distribution in the lower limbs, to directly influence CSF and may be a promising countermeasure to help reduce increases in CSF.NEW & NOTEWORTHY This is the first study to demonstrate the ability of lower body negative pressure to directly influence cerebrospinal fluid surrounding the optic nerve, indicating potential use as a countermeasure for increased cerebrospinal fluid on Earth or in space.

MRI-derived diffusion parameters in the human optic nerve and its surrounding sheath during head-down tilt.

More than half of astronauts present with significant neuro-ophthalmic findings during 6-month missions onboard the International Space Station. Although the underlying cause of this Microgravity Ocular Syndrome is currently unknown, alterations in cerebrospinal fluid dynamics within the optic nerve sheath may play a role. In the presented study, diffusion tensor imaging was used to assess changes in diffusivity of the optic nerve and its surrounding sheath during head-down tilt, a ground-based model of microgravity. Nine healthy male subjects (mean age ± SD: 25 ± 2.4 years; mean body mass index ± SD: 24.1 ± 2.4 kg/m2) underwent 5 head-down tilt conditions: -6°,-12°, -18°,-12° and 1% CO2, and -12° and lower body negative pressure. Mean diffusivity, fractional anisotropy, axial diffusivity, radial diffusivity were quantified in the left and right optic nerves and surrounding sheaths at supine baseline and after 4.5 h head-down tilt for each condition. In the optic nerve sheath, mean diffusivity was increased with all head-down tilt conditions by (Best Linear Unbiased Predictors) 0.147 (SE: 0.04) × 10-3 mm2/s (P < 0.001), axial diffusivity by 0.188 (SE: 0.064) × 10-3 mm2/s (P < 0.001), and radial diffusivity by 0.126 (SE: 0.04) × 10-3 mm2/s (P = 0.0019). Within the optic nerve itself, fractional anisotropy was increased by 0.133 (SE: 0.047) (P = 0.0051) and axial diffusivity increased by 0.135 (SE: 0.08) × 10-3 mm2/s (P = 0.014) during head-down tilt, whilst mean diffusivity and radial diffusivity were unaffected (P > 0.3). These findings could be due to increased perioptic cerebral spinal fluid hydrodynamics during head-down tilt, as well as increased cerebral spinal fluid volume and movement within the optic nerve sheath.