Ware, A. L. | Search bioRxiv

bioRxiv2021

Harmonisation of multi-site MRS data with ComBat

Magnetic resonance spectroscopy (MRS) is a non-invasive neuroimaging technique used to measure brain chemistry in vivo and has been used to study the healthy brain as well as neuropathology in numerous neurological disorders. The number of multi-site studies using MRS are increasing; however, non-biological variability introduced during data collection across multiple sites, such as differences in scanner vendors and site-specific acquisition implementations for MRS, can obscure detection of biological effects of interest. ComBat is a data harmonisation technique that can remove non-biological sources of variance in multisite studies. It has been validated for use with structural and functional MRI metrics but not for MRS metabolites. This study investigated the validity of using ComBat to harmonize MRS metabolites for vendor and site differences. Analyses were performed using data acquired across 20 sites and included edited MRS for GABA+ (N=218) and macromolecule-suppressed GABA data (N=209), as well as standard PRESS data to quantify NAA, creatine, choline, and glutamate (N=195). ComBat harmonisation successfully mitigated vendor and site differences for all metabolites of interest. Moreover, significant associations were detected between sex and choline levels and between age and glutamate and GABA+ levels that were not detectable prior to harmonisation, confirming the importance of removing site and vendor effects in multi-site data. In conclusion, ComBat harmonisation can be successfully applied to MRS data in multi-site MRS studies. HighlightsO_LIMulti-site MRS data contains sources of non-biological variance that can mask biological effects of interest. C_LIO_LIComBat data harmonisation successfully removes variance contributed by scanner and site differences. C_LIO_LIRemoval of this variance revealed biological effects that were previously not detected. C_LIO_LIComBat harmonisation can be successfully applied to MRS data in multi-site MRS studies C_LI

neuroscience↗

bioRxiv2020

White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric msTBI

Annually, approximately 3 million children around the world experience traumatic brain injuries (TBIs), of which up to 20% are characterized as moderate to severe (msTBI) and/or have abnormal imaging findings. Affected children are vulnerable to long-term cognitive and behavioral dysfunction, as injury can disrupt or alter ongoing brain maturation. Post-injury outcomes are highly variable, and there is only limited understanding of how inter-individual differences in outcomes arise. Small sample sizes have also complicated efforts to better understand factors influencing the impact of TBI on the developing brain. White matter (WM) disruption is a critical aspect of TBI neuropathology and diffusion MRI (dMRI) is particularly sensitive to microstructural abnormalities. Here we present the results of a coordinated analysis of dMRI data across ten cohorts from three countries. We had three primary aims: (1) to characterize the nature and extent of WM disruption across key post-injury intervals (acute/subacute - within 2 months, post-acute - 2-6 months, chronic - 6+ months); (2) evaluate the impact of age and sex on WM in the context of injury; and (3) to examine associations between WM and neurobehavioral outcomes. Based on data from 507 children and adolescents (244 with complicated mild to severe TBI and 263 control children), we report widespread WM disruption across all post-injury intervals. As expected, injury severity was a significant contributor to the pattern and extent of WM degradation, but explained less variance in dMRI measures with increasing time since injury, supporting other research indicating that other factors contribute increasingly to outcomes over time. The corpus callosum appears to be particularly vulnerable to injury, an effect that persists years post-TBI. We also report sex differences in the effect of TBI on the uncinate fasciculus (UNC), a structure with a key role in emotion regulation. Females with a TBI had significantly lower fractional anisotropy (FA) in the UNC than those with no TBI, and this phenomenon was further associated with more frequent parent-reported behavioral problems as measured by the Child Behavior Checklist (CBCL). These effects were not detected in males. With future harmonization of imaging and neurocognitive data, more complex modeling of factors influencing outcomes will be possible and help to identify clinically-meaningful patient subtypes.

neuroscience↗