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.

MRI-based quantification of ophthalmic changes in healthy volunteers during acute 15° head-down tilt as an analogue to microgravity.

Spaceflight is known to cause ophthalmic changes in a condition known as spaceflight-associated neuro-ocular syndrome (SANS). It is hypothesized that SANS is caused by cephalad fluid shifts and potentially mild elevation of intracranial pressure (ICP) in microgravity. Head-down tilt (HDT) studies are a ground-based spaceflight analogue to create cephalad fluid shifts. Here, we developed non-invasive magnetic resonance imaging (MRI)-based techniques to quantify ophthalmic structural changes under acute 15° HDT. We specifically quantified: (i) change in optic nerve sheath (ONS) and optic nerve (ON) cross-sectional area, (ii) change in ON deviation, an indicator of ON tortuosity, (iii) change in vitreous chamber depth, and (iv) an estimated ONS Young's modulus. Under acute HDT, ONS cross-sectional area increased by 4.04 mm2 (95% CI 2.88-5.21 mm2, p < 0. 000), while ON cross-sectional area remained nearly unchanged (95% CI -0.12 to 0.43 mm2, p = 0.271). ON deviation increased under HDT by 0.20 mm (95% CI 0.08-0.33 mm, p = 0.002). Vitreous chamber depth decreased under HDT by -0.11 mm (95% CI -0.21 to -0.03 mm, p = 0.009). ONS Young's modulus was estimated to be 85.0 kPa. We observed a significant effect of sex and BMI on ONS parameters, of interest since they are known risk factors for idiopathic intracranial hypertension. The tools developed herein will be useful for future analyses of ON changes in various conditions.

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.

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.

In vivo estimation of optic nerve sheath stiffness using noninvasive MRI measurements and finite element modeling.

The optic nerve sheath (ONS) is biomechanically important. It is acted on by tension due to ocular movements, and by fluid shifts and/or alterations in intracranial pressure (ICP) in human disease, specifically in pathologies leading to intracranial hypertension. It has also been hypothesized that the ONS is acted on by altered ICP in astronauts exposed chronically to microgravity. However, a non-invasive method to quantify ONS biomechanical properties is not presently available; knowledge of such properties is desirable to allow characterization of the biomechanical forces exerted on the optic nerve head and other ocular structures due to the ONS. Thus, the primary objective of this study was to characterize the biomechanical properties (stiffness) of the human ONS in vivo as a necessary step towards investigating the role of ICP in various conditions, including Spaceflight Associated Neuro-ocular Syndrome (SANS). We acquired non-invasive magnetic resonance imaging (MRI) scans of ostensibly healthy subjects (n = 18, age = 30.4 ± 11.6 [mean ± SD] years) during supine and 15-degree head-down-tilt (HDT) postures, and extracted ONS contours from these scans. We then used finite element modeling to quantify ONS expansion due to postural changes and an inverse approach to estimate ONS stiffness. Using this non-invasive procedure, we estimated an in vivo ONS stiffness of 39.2 ± 21.9 kPa (mean ± SD), although a small subset of individuals had very stiff ONS that precluded accurate estimates of their stiffness values. ONS stiffness was not correlated with age and was higher in males than females.

Low-cost, open-source, variable speed and incline treadmill for studying impacts of neonatal locomotion.

There is a need for a small-scale, laboratory treadmill to investigate impacts of neonatal locomotion on neuromuscular and musculoskeletal development in small animal models. Adult mice and rats are routinely assessed using commercially available treadmills, but these treadmills can be relatively expensive and they may lack features needed to evaluate developing animals. Therefore, to overcome these limitations, a new treadmill was designed, built and calibrated. This open-source treadmill was designed specifically for neonatal and postnatal mice and rats, and it fits within a neonatal incubator. By using predominantly off-the-shelf and 3D printed components, and a microcontroller, this treadmill was low cost and easy to reproduce. The design also included variable incline, and a transparent belt and enclosures for video and gait analysis. A touchscreen interface provided user-friendly control over belt speed and run time. Moreover, validation experiments showed high accuracy in belt speed control, allowing for tightly regulated experimental conditions. Overall, this new low-cost, open-source, variable speed and incline treadmill can be used to advance understanding of neonatal locomotion, and neuromuscular and musculoskeletal development.