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.

Harmonization mitigates diffusion MRI scanner effects in infancy: insights from the HEALthy Brain and Childhood Development (HBCD) study

The HEALthy Brain and Childhood Development (HBCD) Study is an ongoing longitudinal initiative to understand population-level brain maturation; however, large-scale studies must overcome site-related variance and preserve biologically relevant signal. In addition to diffusion-weighted magnetic resonance imaging images, the HBCD dataset offers analysis-ready derivatives for scientists to conduct their analysis, including scalar diffusion tensor (DTI) metrics in a predetermined set of bundles. The purpose of this study is to characterize HBCD-specific site effects in diffusion MRI data, which have not been systematically reported. In this work, we investigate the sensitivity of HBCD bundle metrics to scanner model-related variance and address these variations with ComBat-GAM harmonization within the current HBCD data release 1.1 across six scanner models. Following ComBat-GAM, we observe zero statistically significant differences between the distributions from any scanner model following FDR correction and reduce Cohen's f effect sizes across all metrics. Our work underscores the importance of rigorous harmonization efforts in large-scale studies, and we encourage future investigations of HBCD data to control for these effects.