Longitudinal MRI-visible perivascular space (PVS) changes with long-duration spaceflight

Abstract

Humans are exposed to extreme environmental stressors during spaceflight and return with alterations in brain structure and shifts in intracranial fluids. To date, no studies have evaluated the effects of spaceflight on perivascular spaces (PVSs) within the brain, which are believed to facilitate fluid drainage and brain homeostasis. Here, we examined how the number and morphology of magnetic resonance imaging (MRI)-visible PVSs are affected by spaceflight, including prior spaceflight experience. Fifteen astronauts underwent six T₁-weighted 3 T MRI scans, twice prior to launch and four times following their return to Earth after ~ 6-month missions to the International Space Station. White matter MRI-visible PVS number and morphology were calculated using an established, automated segmentation algorithm. We validated our automated segmentation algorithm by comparing algorithm PVS counts with those identified by two trained raters in 50 randomly selected slices from this cohort; the automated algorithm performed similarly to visual ratings (r(48) = 0.77, p < 0.001). In addition, we found high reliability for four of five PVS metrics across the two pre-flight time points and across the four control time points (ICC(3,k) > 0.50). Among the astronaut cohort, we found that novice astronauts showed an increase in total PVS volume from pre- to post-flight, whereas experienced crewmembers did not (p = 0.020), suggesting that experienced astronauts may exhibit holdover effects from prior spaceflight(s). Greater pre-flight PVS load was associated with more prior flight experience (r = 0.60-0.71), though these relationships did not reach statistical significance (p > 0.05). Pre- to post-flight changes in ventricular volume were not significantly associated with changes in PVS characteristics, and the presence of spaceflight associated neuro-ocular syndrome (SANS) was not associated with PVS number or morphology. Together, these findings demonstrate that PVSs can be consistently identified on T₁-weighted MRI scans, and that spaceflight is associated with PVS changes. Specifically, prior spaceflight experience may be an important factor in determining PVS characteristics.

Figure 1

PVSs identified on a single astronaut. Here we depict a binary mask of PVSs for a single astronaut at the last pre-flight time point (Launch-60 days), for illustrative purposes. PVSs are shown in red, overlaid onto this individual’s native space 3D-rendered white matter segment (left) as well as several sagittal slices of their skull stripped native space structural scan (right). The blue box shows a zoomed-in view of one PVS, inside the blue circle.

Figure 2

Correlation of total PVS number obtained from automated algorithm and visual rating. Here we depict the strong positive correlation between the algorithm-generated total PVS number, and the average total PVS number (on the same slice for each participant), as counted by two blinded independent raters for 50 randomly selected MRI scans from this astronaut cohort. Note that points are jittered by x = 0.15 and y = 0.15, for ease of visual interpretation (as otherwise, many points would be overlapping with one another).

Figure 3

Changes in PVS metrics and ventricular volume from pre- to post-flight. Group average PVS characteristics are depicted for each of the four control group time points (gray, left panels) and for each of the six astronaut time points (right panels). The astronaut data are split into novice (green) and experienced (purple) subgroups. Bars represent standard error. The width of the green and purple boxes indicates the average flight duration for novice and experienced astronauts, respectively. *Indicates a statistically significant (p < 0.05) group difference between the novice and experienced astronauts for changes in total PVS volume with spaceflight. ***Indicates a statistically significant (p < 0.001) change in ventricular volume from pre- to post-flight. The second astronaut time point depicts group-average data for n = 8 (instead of 9) novice astronauts; the final astronaut time point depicts group-average data for n = 13 (instead of 15) experienced astronauts (see “Methods” for details on these missing data). We included only complete control group datasets, so n = 11 for all control time points. WM white matter, TIV total intracranial volume.