Multisite Harmonization of Structural DTI Networks in Children: An A-CAP Study

Adrian I Onicas; Ashley L Ware; Ashley D Harris; Miriam H Beauchamp; Christian Beaulieu; William Craig; Quynh Doan; Stephen B Freedman; Bradley G Goodyear; Roger Zemek; Keith Owen Yeates; Catherine Lebel

doi:10.3389/fneur.2022.850642

Multisite Harmonization of Structural DTI Networks in Children: An A-CAP Study

Front Neurol. 2022 Jun 17:13:850642. doi: 10.3389/fneur.2022.850642. eCollection 2022.

Authors

Adrian I Onicas^{1

2}, Ashley L Ware^{1

3

4

5}, Ashley D Harris^{4

5

6}, Miriam H Beauchamp⁷, Christian Beaulieu⁸, William Craig⁹, Quynh Doan¹⁰, Stephen B Freedman¹¹, Bradley G Goodyear^{4

6}, Roger Zemek¹², Keith Owen Yeates^{1

4

5}, Catherine Lebel^{4

5

6}

Affiliations

¹ Department of Psychology, University of Calgary, Calgary, AB, Canada.
² MoMiLab Research Unit, IMT School for Advanced Studies Lucca, Lucca, Italy.
³ Department of Neurology, University of Utah, Salt Lake City, UT, United States.
⁴ Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
⁵ Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
⁶ Department of Radiology, University of Calgary, Calgary, AB, Canada.
⁷ Department of Psychology, University of Montreal and CHU Sainte-Justine Hospital Research Center, Montreal, QC, Canada.
⁸ Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada.
⁹ University of Alberta and Stollery Children's Hospital, Edmonton, AB, Canada.
¹⁰ Department of Pediatrics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.
¹¹ Departments of Pediatrics and Emergency Medicine, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
¹² Department of Pediatrics and Emergency Medicine, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.

Abstract

The analysis of large, multisite neuroimaging datasets provides a promising means for robust characterization of brain networks that can reduce false positives and improve reproducibility. However, the use of different MRI scanners introduces variability to the data. Managing those sources of variability is increasingly important for the generation of accurate group-level inferences. ComBat is one of the most promising tools for multisite (multiscanner) harmonization of structural neuroimaging data, but no study has examined its application to graph theory metrics derived from the structural brain connectome. The present work evaluates the use of ComBat for multisite harmonization in the context of structural network analysis of diffusion-weighted scans from the Advancing Concussion Assessment in Pediatrics (A-CAP) study. Scans were acquired on six different scanners from 484 children aged 8.00-16.99 years [Mean = 12.37 ± 2.34 years; 289 (59.7%) Male] ~10 days following mild traumatic brain injury (n = 313) or orthopedic injury (n = 171). Whole brain deterministic diffusion tensor tractography was conducted and used to construct a 90 x 90 weighted (average fractional anisotropy) adjacency matrix for each scan. ComBat harmonization was applied separately at one of two different stages during data processing, either on the (i) weighted adjacency matrices (matrix harmonization) or (ii) global network metrics derived using unharmonized weighted adjacency matrices (parameter harmonization). Global network metrics based on unharmonized adjacency matrices and each harmonization approach were derived. Robust scanner effects were found for unharmonized metrics. Some scanner effects remained significant for matrix harmonized metrics, but effect sizes were less robust. Parameter harmonized metrics did not differ by scanner. Intraclass correlations (ICC) indicated good to excellent within-scanner consistency between metrics calculated before and after both harmonization approaches. Age correlated with unharmonized network metrics, but was more strongly correlated with network metrics based on both harmonization approaches. Parameter harmonization successfully controlled for scanner variability while preserving network topology and connectivity weights, indicating that harmonization of global network parameters based on unharmonized adjacency matrices may provide optimal results. The current work supports the use of ComBat for removing multiscanner effects on global network topology.

Keywords: ComBat; diffusion MRI; graph theory; multisite harmonization; pediatric mild traumatic brain injury; structural connectome.