Sensitivity of diffusion-tensor and correlated diffusion imaging to white-matter microstructural abnormalities: application in COVID-19

There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion MRI methods for detecting such effects. In this work, the sensitivities of three single-shell-compatible diffusion MRI modeling methods are compared for detecting the effect of COVID-19, including diffusion-tensor imaging, diffusion-tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self-isolated patients at baseline and 3-month follow-up, along with age- and sex-matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single-shell methods to demonstrate COVID-19-related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID-19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID-19 related white-matter microstructural pathology manifests as a change in water diffusivity. Interestingly, different b-values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3-month follow-up, likely due to the limited size of the follow-up cohort. To summarize, correlated diffusion imaging is shown to be a sensitive single-shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection.

Decreased cerebral blood flow in non-hospitalized adults who self-isolated due to COVID-19

The long-term consequences of coronavirus disease 2019 (COVID-19) on brain physiology and function are not yet well understood. From the recently described NeuroCOVID-19 study, we examined cerebral blood flow (CBF) in 50 participants recruited to one of two groups: 1) adults who previously self-isolated at home due to COVID-19 (n = 39; 116.5 {+/-} 62.2 days since positive diagnosis), or 2) controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (n = 11). Participants underwent arterial spin labeling magnetic resonance imaging at 3 T to yield measures of CBF. Voxel-wise analyses of CBF were performed to assess for between-group differences, after controlling for age and sex. Relative to controls, the COVID-19 group exhibited decreased CBF in the thalamus, orbitofrontal cortex, and regions of the basal ganglia. Within the COVID-19 group, CBF differences in occipital and parietal regions were observed between those with (n = 11) and without (n = 28) self-reported on-going fatigue. These results suggest long-term changes in brain physiology in adults across the post-COVID-19 timeframe. Moreover, CBF may aid in understanding the heterogeneous symptoms of the post-COVID-19 condition. Future longitudinal studies are needed to further characterize the consequences of COVID-19 on the brain.