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

Abstract

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. Results also demonstrate, for the first time, more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. Whereas correlated diffusion imaging can be successfully applied using single-shell diffusion data, different b-values also confer different sensitivities to these two opposing effects. No significant difference was observed in patients at the 3-month follow-up. To summarize, correlated diffusion imaging is shown to be a sensitive single-shell diffusion analysis approach that allowed us to uncovered opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection.

Long COVID: neurological manifestations - an updated narrative review

“…In the first study, low diffusion restriction in frontal circuits and high diffusion restriction in cerebellum were found in patients with COVID-19 compared to controls 32 . In the second study, Tellet et al demonstrated reduced cerebral blood flow (CBF) in the thalamus, basal ganglia, and orbitofrontal cortex in COVID-19 patients compared to controls 33 . With regard to possible fluid biomarkers, in patients with long COVID there is an activation of the inflammasome mediated by SARS-Cov-2 and a subsequent dysregulated inflammatory response, with consequent persistent elevation of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha 26,[34][35][36] .…”

“…Douaud et al described, using brain MRI, gray matter atrophy in the orbitofrontal cortex and parahippocampal gyrus in 401 post-COVID-19 patients compared with pre-COVID-19 examination of the same patients 28 . Other promising magnetic resonance imaging (MRI) techniques in the study of these patients are diffusion tensor imaging (DTI) and arterial spin labeling, which were even used in patients with long COVID by Kim et al and Teller et al, respectively 32 , 33 . In the first study, low diffusion restriction in frontal circuits and high diffusion restriction in cerebellum were found in patients with COVID-19 compared to controls 32 .…”

“…Other promising magnetic resonance imaging (MRI) techniques in the study of these patients are diffusion tensor imaging (DTI) and arterial spin labeling, which were even used in patients with long COVID by Kim et al and Teller et al, respectively 32 , 33 . In the first study, low diffusion restriction in frontal circuits and high diffusion restriction in cerebellum were found in patients with COVID-19 compared to controls 32 . In the second study, Tellet et al demonstrated reduced cerebral blood flow (CBF) in the thalamus, basal ganglia, and orbitofrontal cortex in COVID-19 patients compared to controls 33 .…”