Evaluation of neuroCombat and deep learning harmonization for multi-site magnetic resonance neuroimaging in youth with prenatal alcohol exposure

In cases of prevalent diseases and disorders, such as Prenatal Alcohol Exposure (PAE), multi-site data collection allows for increased study samples. However, multi-site studies introduce additional variability through heterogeneous collection materials, such as scanner and acquisition protocols, which confound with biologically relevant signals. Neuroscientists often utilize statistical methods on image-derived metrics, such as volume of regions of interest, after all image processing to minimize site-related variance. HACA3, a deep learning harmonization method, offers an opportunity to harmonize image signals prior to metric quantification; however, HACA3 has not yet been validated in a pediatric cohort. In this work, we investigate HACA3's ability to remove site-related variance and preserve biologically relevant signal compared to a statistical method, neuroCombat, and pair HACA3 processing with neuroCombat to evaluate the efficacy of multiple harmonization methods in a pediatric (age 7 to 21) population across three unique scanners with controls and cases of PAE with downstream MaCRUISE volume metrics. We find that HACA3 qualitatively improves inter-site contrast variations, but statistical methods reduce greater site-related variance within the MaCRUISE volume metrics following an ANCOVA test, and HACA3 relies on follow-up statistical methods to approach maximal biological preservation in this context.