Widespread white matter oedema in subacute COVID-19 patients with neurological symptoms

Abstract

While neuropathological examinations in patients who died from COVID-19 revealed inflammatory changes in cerebral white matter, cerebral MRI frequently fails to detect abnormalities even in the presence of neurological symptoms. Application of multi-compartment diffusion microstructure imaging (DMI), that detects even small volume shifts between the compartments (intra-axonal, extra-axonal and free water/CSF) of a white matter model, is a promising approach to overcome this discrepancy. In this monocentric prospective study, a cohort of 20 COVID-19 inpatients (57.3 ± 17.1 years) with neurological symptoms (e.g. delirium, cranial nerve palsies) and cognitive impairments measured by the Montreal Cognitive Assessment (MoCA test; 22.4 ± 4.9; 70% below the cut-off value <26/30 points) underwent DMI in the subacute stage of the disease (29.3 ± 14.8 days after positive PCR). A comparison of whole-brain white matter DMI parameters with a matched healthy control group (n = 35) revealed a volume shift from the intra- and extra-axonal space into the free water fraction (V-CSF). This widespread COVID-related V-CSF increase affected the entire supratentorial white matter with maxima in frontal and parietal regions. Streamline-wise comparisons between COVID-19 patients and controls further revealed a network of most affected white matter fibres connecting widespread cortical regions in all cerebral lobes. The magnitude of these white matter changes (V-CSF) was associated with cognitive impairment measured by the MoCA test (r = −0.64, P = 0.006) but not with olfactory performance (r = 0.29, P = 0.12). Furthermore, a non-significant trend for an association between V-CSF and interleukin-6 emerged (r = 0.48, P = 0.068), a prominent marker of the COVID-19 related inflammatory response. In 14/20 patients who also received cerebral 18F-FDG PET, V-CSF increase was associated with the expression of the previously defined COVID-19-related metabolic spatial covariance pattern (r = 0.57; P = 0.039). In addition, the frontoparietal-dominant pattern of neocortical glucose hypometabolism matched well to the frontal and parietal focus of V-CSF increase. In summary, DMI in subacute COVID-19 patients revealed widespread volume shifts compatible with vasogenic oedema, affecting various supratentorial white matter tracts. These changes were associated with cognitive impairment and COVID-19 related changes in 18F-FDG PET imaging.

Application of diffusion microstructure imaging in musculoskeletal radiology — translation from head to shoulders

“…Our DMI approach further considers an additional free fluid compartment (V-ISO). In a previous study, our DMI approach was reported to be highly sensitive to discrete shifts of microstructural compartments otherwise not detectable on conventional MRI [19]. DMI was also more sensitive in detecting pathological changes in brain tissue in the context of neurodegeneration than DTI [18].…”

“…The arm was positioned in neutral zero position. For chemical shift encoding-based water-fat separation of the RC, a transverse-prescribed two-point T1w Dixon sequence was acquired with the following parameters: repetition time (TR) = 4.2 ms, echo times (TE) = 1.23 and 2.46 ms, flip angle = 5°, GRAPPA factor = 2, voxel size = 0.7 × 0.7 × 3.0 mm 3 , phase encoding direction = A/P, consecutive slices = 48, scan time = 54 s. The dMRI sequence was adapted from the previously published brain-specific sequence [19] to address the specific requirements for dMRI in the musculature [27][28][29] resulting in the following parameters: transverse orientation, 23 consecutive slices, voxel size = 2.0 × 2.0 × 4 mm 3 , TR = 4500 ms, TE = 90 ms, bandwidth = 2222 Hz/Px, GRAPPA factor = 2, 12 diffusion-encoding gradient directions, b-factors = 600 and 1000 s/mm 2 ; scan time = 5:35 min.…”

“…Recently, advanced multicompartment techniques like diffusion microstructure imaging (DMI) have provided substantial additional value in neuroimaging and allowed for even more specific insights into the microstructural integrity of tissue compared to DTI [17][18][19][20]. Rather than only providing information on the directionality and orientation of the diffusivity within a voxel as in DTI, DMI approximates the distribution of three microstructural compartments per voxel.…”

Brain microstructural changes and fatigue after COVID-19

“…These changes were associated with cognitive impairment and COVID-19-related changes in 18F-FDG PET imaging. 42 Reduced axonal densities have been detected in patients after recovery from COVID-19, 1 year after infection in a sample consisting primarily of hospitalized patients. 43 To our knowledge, there is no serial d-MRI study following up on a non-hospitalized sample of patients with milder COVID-19 forms.…”

Brain microstructural changes and fatigue after COVID-19

“…However, FW-corrected DTI measurements are more sensitive to detect changes in some tracts (arcuate and superior longitudinal fascicles). In a recent study, multicompartment diffusion microstructure imaging in inpatients with subacute COVID-19 with neurological symptoms revealed widespread volume shifts compatible with vasogenic edema, affecting various white matter tracts ( 43 ). Redistribution with decreasing intra-axonal and extra-axonal volumes and increasing free water/CSF fraction was observed at a mean follow-up of 30 days ( 43 ).…”