Table 1.

Summary of MRI findings from studies conducted in US astronauts and Russian cosmonauts pre and post spaceflight and potential clinical correlates where applicable.

Study	Population	Imaging protocol	Main findings
Demertzi et al. 15	n = 1 LD. Pre and post flight scans	fMRI (3 T): -Resting state connectivity -Active mental imagery connectivity	- Reduced intrinsic connectivity in R insula and ventral posterior cingulate cortex; reduced connectivity between R motor cortex and L cerebellum (resting state fMRI) -Increased activation of the supplementary motor area (active imagery fMRI)
Koppelmans et al.13	n = 27, 13 SD and 14 LD. Pre- and post flight scans	T2-weighted MRI (3 T) -Gray matter volume	-Widespread GM decreases in frontal and temporal poles -Focal GM decreases in R inferior frontal gyrus, R frontal pole, L temporal lobe, L insular cortex. Changes greater in LD crew.-Focal GM increases in medial primary somatosensory and motor cortices
Roberts et al.18	n = 34, 16 SD and 18 LD Pre- and post flight scans	T2-weighted MRI (3 T) -Static structure changes T1-weightedl MRI (3 T), cine-clips -Brain position and CSF spaces	-Narrowing of CSF spaces, increase in width of 3rd ventricle, upward movement of cerebellar tonsils. Changes greater in LD crew.-Upward shift of brain and brain stem, narrowing of CSF spaces at the vertex, rotation of the cerebral aqueduct, stretching of the pituitary stalk. Occurred at higher rates in LD crew.
Alperin et al.14	n = 17, 7 SD and 10 LD Pre- and post flight scans 1 month follow up scan	T1-weighted MRI (3 T) -Ventricular volumes T2-weighted FLAIR MRI (3 T) -WMH	-Increased periventricular WMH in LD group only. -No significant increase in deep WMH -Increase in total ventricular volume, significantly positively associated with periventricular WMH -Partial reversal of observed increases at 1-month follow-up scan
Van Ombergen et al.20	n = 10 LD. Pre- and post flight scans 7-month follow-up scan	T1-weighted MRI (3 T) -Brain tissue and CSF volumes	-GM volumes decreased in orbitofrontal and temporal cortexes, largely recovered by 7-month follow-up scan. -Cerebral WM volumes globally reduced at 7-month follow-up scan compared to early postflight scan. -CSF spaces and ventricles increased in volume (maximal at third ventricle), decreased CSF volume below the vertex. -At 7-month follow-up, CSF volume in the ventricles partially returned to preflight values, while CSF volume in subarachnoid space increased.
Roberts et al.19	n = 19, 7 SD and 12 LD Pre- and post flight scans	T1-weighted MRI (3 T) -Brain tissue and CSF volumes	-Increase in total ventricular volume in LD crew. Significant increase in lateral ventricles and third ventricle, but not in fourth ventricle. Change in ventricular volume associated with increasing flight duration and decreasing crewmember age. -Crowding of parenchyma at the vertex (supplementary motor, premotor, primary sensorimotor regions) and displacement of brain tissue surrounding the ventricles seen in LD crew only. -Clinical Correlate: Change in L caudate associated with poorer postural control, change in R lower extremity primary motor area/midcingulate associated with longer time on seated egress and walk test. Reduced accuracy on WinSCAT code substation learning subtest, faster reaction times associated with smaller changes in volume of bilateral optic radiations and splenium
Van Ombergen et al. 201921	n = 11, LD Pre- and post flight scans, 7-month follow-up	T1- weighted MRI (3 T) -CSF volumes	-Increased lateral ventricle, third ventricle and total ventricular volume after LD spaceflight, with residual baseline increases at 7 months. No significant change in fourth ventricle. -Ventricular volume increases associated with increasing mission duration
Riascos et al.17	n = 19, 10 SD and 9 LD Pre- and post flight scans	T1-weighted MRI (3 T) -Brain tissue volume Diffusion-weighted MRI (3 T) -WM microstructure, GM diffusivity	-Trend for cortical thinning of R occipital lobe; reduced volume of L. thalamus; increased lateral ventricular volume. -WM changes in R posterior thalamic radiations, trend towards greater effects in LD crew.
Lee et al.16	n = 15, 7 SD and 8 LD Pre- and post flight scans	Diffusion-weighted MRI (3 T) -WM microstructure, GM diffusivity	-Increased FW volume in frontal, temporal and occipital lobes after spaceflight, with decreased FW volume at the vertex. -WM changes in R. SLF, ILF, IFOF, CST, ICP, MCP and white matter structures underlying the precentral and postcentral gyrus, supramarginal gyrus and angular gyrus. -Greater WM organization postflight in cerebellar white matter in LD crew compared to SD crew -Clinical Correlate: Microstructural changes in the SLF were greater in individuals with greater decreases in balance control
Pechenkova et al.23	n = 11 LD, compared to HC Pre- and post flight scans	fMRI (3 T): -Resting state connectivity -Plantar stimulation paradigm	-Stimulation-specific increase in connectivity of R posterior supramarginal gyrus with the rest of the brain -Increased connectivity between R and L posterior insula; decreased connectivity between posterior cerebellum and primary visual cortex; decreased connectivity between anterior cerebellum and R parietal cortex -Connectivity modifications at vestibular nuclei, R parietal cortex, anterior cerebellar network, R posterior insula and L posterior insula -Clinical Correlate: Space motion sickness severity associated with connectivity between R posterior supramarginal gyrus and L insular region
Kramer et al.22	n = 11, LD Pre- and post-flight scans 1, 3, 9, 12-month follow-up scans	T1- and T2 weighted MRI (3 T) -Brain tissue and CSF volumes -Pituitary evaluation T1-weighted MRI (3 T), cine-clips -Quantitative CSF Flow	-Expansion of total brain and CSF volumes after LD spaceflight, with persistent elevation 1 year after spaceflight. Largely driven by global WM volume and lateral ventricular volume increases -Increased aqueductal stroke volume and CSF peak-to-peak velocity magnitude -Pituitary depression seen in 6/11 crewmembers
Hupfield et al.24	n = 12, LD (6-month, n = 10, 12-month n = 2), compared to HC Pre and post-flight scans 6 month follow-up scans	T1-weighted MRI (3 T) -Brain tissue and CSF volumes Diffusion-weighted MRI (3 T) -FW shifts	-Significantly enlarged ventricular volumes in all 6-month mission astronauts, and 1 of 2 12-month mission astronauts compared to control. Partial resolution of increased volumes seen 6-months post-flight in 50% of subjects -Increased GM volume and cortical thickness in the SMA, pre- and postcentral gyri in the 6-month mission astronauts and 1 of 2 12-month mission astronauts, largely recovered on 6-month follow-up scan
Jillings et al.25	N = 11, LD, compared to HC Pre and post-flight scans 7 month follow-up scans	Diffusion-weighted MRI (3 T) -Multi-tissue spherical deconvolution for GM, WM and CSF volumes	-GM changes driven by local volume shifts rather than tissue loss, largely reversed at 7-month follow up -WM volume increases in the cerebellum, CST, PMC -GM volume increases in the basal ganglia -Larger visual acuity decreases post-flight associated with greater ventricular expansion

CSF cerebrospinal fluid, CST corticospinal tract, FW free water, GM gray matter, HC healthy control, ICP inferior cerebellar peduncle, IFOF inferior fronto-occipital fasiculus, ILF inferior longitudinal fasiculus, L left, LD long duration, PMC primary motor cortex, MCP middle cerebellar peduncle, R right, SD short duration, SLF superior longitudinal fasiculus, SMA supplementary motor area, WMH white matter hyperintensities.