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

Nick Teller, Jordan A. Chad, Alexander Wong, Hayden Gunraj, Xiang Ji, Bradley J MacIntosh, Asaf Gilboa, Eugenie Roudaia, Allison Sekuler, Benjamin Lam, Chris Heyn, Sandra E Black, Simon J Graham, J. Jean Chen
doi: https://doi.org/10.1101/2022.09.29.510004
Nick Teller
1Rotman Research Institute, Baycrest Health Sciences
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Jordan A. Chad
1Rotman Research Institute, Baycrest Health Sciences
2Department of Medical Biophysics, University of Toronto
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Alexander Wong
4Department of System Design Engineering, University of Waterloo
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Hayden Gunraj
4Department of System Design Engineering, University of Waterloo
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Xiang Ji
5Sunnybrook Research Institute, Sunnybrook Health Science Centre
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Bradley J MacIntosh
2Department of Medical Biophysics, University of Toronto
5Sunnybrook Research Institute, Sunnybrook Health Science Centre
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Asaf Gilboa
1Rotman Research Institute, Baycrest Health Sciences
6Department of Psychology, University of Toronto
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Eugenie Roudaia
1Rotman Research Institute, Baycrest Health Sciences
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Allison Sekuler
1Rotman Research Institute, Baycrest Health Sciences
6Department of Psychology, University of Toronto
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Benjamin Lam
5Sunnybrook Research Institute, Sunnybrook Health Science Centre
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Chris Heyn
5Sunnybrook Research Institute, Sunnybrook Health Science Centre
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Sandra E Black
5Sunnybrook Research Institute, Sunnybrook Health Science Centre
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Simon J Graham
2Department of Medical Biophysics, University of Toronto
5Sunnybrook Research Institute, Sunnybrook Health Science Centre
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J. Jean Chen
1Rotman Research Institute, Baycrest Health Sciences
2Department of Medical Biophysics, University of Toronto
3Institute of Biomedical Engineering, University of Toronto
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  • For correspondence: jchen@research.baycrest.org
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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, 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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 29, 2022.
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Sensitivity of diffusion-tensor and correlated diffusion imaging to white-matter microstructural abnormalities: application in COVID-19
Nick Teller, Jordan A. Chad, Alexander Wong, Hayden Gunraj, Xiang Ji, Bradley J MacIntosh, Asaf Gilboa, Eugenie Roudaia, Allison Sekuler, Benjamin Lam, Chris Heyn, Sandra E Black, Simon J Graham, J. Jean Chen
bioRxiv 2022.09.29.510004; doi: https://doi.org/10.1101/2022.09.29.510004
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Sensitivity of diffusion-tensor and correlated diffusion imaging to white-matter microstructural abnormalities: application in COVID-19
Nick Teller, Jordan A. Chad, Alexander Wong, Hayden Gunraj, Xiang Ji, Bradley J MacIntosh, Asaf Gilboa, Eugenie Roudaia, Allison Sekuler, Benjamin Lam, Chris Heyn, Sandra E Black, Simon J Graham, J. Jean Chen
bioRxiv 2022.09.29.510004; doi: https://doi.org/10.1101/2022.09.29.510004

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