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. 2020 Aug:25:100484.
doi: 10.1016/j.eclinm.2020.100484. Epub 2020 Aug 3.

Cerebral Micro-Structural Changes in COVID-19 Patients - An MRI-based 3-month Follow-up Study

Yiping Lu  1 , Xuanxuan Li  1 , Daoying Geng  1 , Nan Mei  1 , Pu-Yeh Wu  2 , Chu-Chung Huang  3 , Tianye Jia  4 , Yajing Zhao  1 , Dongdong Wang  1 , Anling Xiao  5 , Bo Yin  1
Affiliations

Cerebral Micro-Structural Changes in COVID-19 Patients - An MRI-based 3-month Follow-up Study

Yiping Lu et al. EClinicalMedicine. 2020 Aug.

Abstract

Background: Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2.

Methods: In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information.

Findings: In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected p value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl's gyrus, and Global MD of WM were found to correlate with memory loss (p value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss (p value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level (p value <0.05).

Interpretation: Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2.

Funding: Shanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab.

Keywords: 3D-T1WI, 3 Dimensional T1-weighted Images; AAL-3, Automated Anatomical Labelling Atlas-3; ACE-2, Angiotensin Converting Enzyme-2; AD, Axial Diffusivity; CNS, Central Nervous System; COVID-19; COVID-19, Coronavirus Disease; CR, Corona Radiata; CSF, Cerebral Spinal Fluid; Central Nervous System Diseases; DICOM, Digital Imaging and Communications in Medicine; DTI, Diffusion Tensor Imaging; Diffusion Tensor Imaging; EC, External Capsule; FA, Fractional Anisotropy; FOV, Field of View; GM, Gray Matter; GMV, Gray Matter Volume; HIV, Human Immunodeficiency Virus; HSV, Herpes Simplex Virus; JEV, Japanese Encephalitis Virus; LDH, Lactate Dehydrogenase; MD, Mean Diffusivity; MPRAGE, Magnetization Prepared Rapid Gradient Echo; Neuroimaging; OB, Olfactory Bulb; PCR, Polymerase Chain Reaction; Prospective studies; RD, Radial Diffusivity; SARS-CoV, Severe Acute Respiratory Syndrome Coronavirus; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus-2; SFF, Superior Frontal-occipital Fasciculus; TBSS, Track-based Spatial Statistics; TE, Echo Time; TR, Repetition Time; UF, Uncinate Fasciculus; URTI, Upper Respiratory Tract Infection; VBM, Voxel-based Morphometry; WBC, White Blood Cell; WHO, World Health Organization; WM, White Matter; WMV, White Matter Volume.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This paper has never been published elsewhere.

Figures

Figure 1
Figure 1
The atlas-based imaging processing workflow
Figure 2
Figure 2
The regions with statistically significant differences in the volumes and diffusion indices of the COVID-19 group compared with the control group. The regions with relative higher mean values in the COVID-19 group were marked as red, and the regions with relative lower mean values in the COVID-19 group were marked as blue. GMV: gray matter volume; MD GM: mean diffusivity of gray matter; MD WM: mean diffusivity of white matter; AD WM: axial diffusivity of white matter.
Figure 3
Figure 3
Correlation among brain scores, regional volumes and diffusion indices with neurological symptoms during acute stage. The range of correlation coeffcients (CCs) is between -1 to 1. The numbers in the figure are CCs * 100 for the convenience of display. Abbreviations: GMV: Gray Matter Volume; WMV: White Matter Volume; GM: Gray Matter; WM: White Matter; FA: Factional Anisotropy; MD: Mean Diffusivity; AD: Axial Diffusivity; RD: Radial Diffusivity; CR: Corona Radiata; EC: External Capsule; NAC: Nucleus Accumbens; L: Left; R: Right.
Figure 4
Figure 4
Correlation among brain scores, regional volumes and diffusion indices with neurological symptoms at follow-up visit. The range of correlation coeffcients (CCs) is between -1 to 1. The numbers in the figure are CCs * 100 for the convenience of display. Abbreviations: GMV: Gray Matter Volume; WMV: White Matter Volume; GM: Gray Matter; WM: White Matter; FA: Factional Anisotropy; MD: Mean Diffusivity; AD: Axial Diffusivity; RD: Radial Diffusivity; CR: Corona Radiata; EC: External Capsule; NAC: Nucleus Accumbens; L: Left; R: Right.
Figure 5
Figure 5
A scatter plot with regression was produced for the correlation between LDH (U/L) and global GMV (cm3). LDH: Lactate Dehydrogenase; GMV: Gray Matter Volume
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