Figure 1
From: Brain temperature and free water increases after mild COVID-19 infection
Neuroimaging metrics before and after mild COVID-19. (A) Voxelwise maps visualize regions showing significant pre- to post-COVID changes as determined by repeated measures ANOVAs. Brain regions showing the most pronounced post-COVID-19 effects are visualized using cluster-level p < 0.001 (top), with the same axial slices visualized with p < 0.05 (bottom). There were no changes in voxelwise FICVF or ODI. (i) Brain temperature (TCRE) increases (p < 0.001) were most pronounced in the left (L) medial orbitofrontal cortex and L inferior frontal gyrus (L IFG) pars orbitalis (top). When visualized using p < 0.05 (bottom), TCRE increases extended to include the L inferior parietal lobule, L and right (R) superior temporal gyri, R middle cingulate cortex (MCC), and areas comprising the boundary between the L precentral and postcentral gyri. (ii) Fractional isotropic volume fraction (FISO), which measures extracellular free water (i.e., a measure of edema), significantly (p < 0.001; top) increased after COVID-19 in the L medial temporal pole, right (R) middle frontal gyrus, R IFG (pars Opercularis), R anterior cingulate cortex (ACC), L and R cerebellum (crus II), and R superior occipital gyrus. When visualized using p < 0.05 (bottom), FISO increases extended to include the L superior medial and middle temporal gyri, L paracentral lobule, as well as the L precentral and postcentral gyri; on the right, FISO increases were also found in the R precentral and angular gyri and the R inferior parietal lobule. (iii) Significant post-COVID-19 grey matter volume (GMV) decreases (p < 0.001) were observed in the R IFG and L cerebellar crus II (A.iii, top). When visualized using p < 0.05 (A.iii, bottom), GMV decreases extended more evenly across both hemispheres, in regions including the R MCC, L ACC, L and R middle temporal cortices, L and R superior frontal gyri, and L and R cerebellum (VIII). (B) Box-and-whisker plots illustrate the distribution and variation of TCRE (left) and FISO (right) in regions of interest (ROIs) where mixed-effects analysis found pre- to post-COVID-19 increases. Boxes represent the interquartile range (IQR), which contains the middle 50% of the data. The line inside the box represents the median value, and whiskers extend to the minimum and maximum values within 1.5 times the IQR. Participants’ individual data points denote the mean for each represented by the dash symbol ("–") and are colored based on the timepoint. Pre-COVID-19 data points are shown in blue, while post-COVID-19 data points are shown in orange. In the primary olfactory cortex, (i) significant post-COVID-19 TCRE elevations were predominately observed in the left hemisphere, specifically in the anterior olfactory nucleus (p = 0.04), frontal piriform (p = 0.02), and olfactory tubercle (p = 0.007). Additionally, statistically significant post-COVID-19 FISO increases (ii) were found in secondary olfactory areas, including crus 2 of the L cerebellum (p = 0.02), L and R middle frontal gyri (p = 0.001 for both), and L and R thalami (p = 0.002 and p = 0.003, respectively). For each plot, pre-COVID-19 data are colored in blue, while post-COVID-19 data are colored orange. MRSI-t volumetric magnetic resonance spectroscopic imaging and thermometry, CRE creatine, TCRE brain temperature measured by MRSI-t with CRE as the reference metabolite, FISO fractional isotropic volume fraction, ODI orientation dispersion index, FICVF fractional intracellular volume fraction, GMV grey matter volume, olf olfactory, AON anterior olfactory nucleus, L left, R right, P posterior, ROI region of interest.
