Multisite test-retest reliability and compatibility of brain metrics derived from FreeSurfer versions 7.1, 6.0, and 5.3.

Automatic neuroimaging processing tools provide convenient and systematic methods for extracting features from brain magnetic resonance imaging scans. One tool, FreeSurfer, provides an easy-to-use pipeline to extract cortical and subcortical morphometric measures. There have been over 25 stable releases of FreeSurfer, with different versions used across published works. The reliability and compatibility of regional morphometric metrics derived from the most recent version releases have yet to be empirically assessed. Here, we used test-retest data from three public data sets to determine within-version reliability and between-version compatibility across 42 regional outputs from FreeSurfer versions 7.1, 6.0, and 5.3. Cortical thickness from v7.1 was less compatible with that of older versions, particularly along the cingulate gyrus, where the lowest version compatibility was observed (intraclass correlation coefficient 0.37-0.61). Surface area of the temporal pole, frontal pole, and medial orbitofrontal cortex, also showed low to moderate version compatibility. We confirm low compatibility between v6.0 and v5.3 of pallidum and putamen volumes, while those from v7.1 were compatible with v6.0. Replication in an independent sample showed largely similar results for measures of surface area and subcortical volumes, but had lower overall regional thickness reliability and compatibility. Batch effect correction may adjust for some inter-version effects when most sites are run with one version, but results vary when more sites are run with different versions. Age associations in a quality controlled independent sample (N = 106) revealed version differences in results of downstream statistical analysis. We provide a reference to highlight the regional metrics that may yield recent version-related inconsistencies in published findings. An interactive viewer is provided at http://data.brainescience.org/Freesurfer_Reliability/.

Genetic map of regional sulcal morphology in the human brain from UK biobank data.

Genetic associations with macroscopic brain structure can provide insights into brain function and disease. However, specific associations with measures of local brain folding are largely under-explored. Here, we conducted large-scale genome- and exome-wide associations of regional cortical sulcal measures derived from magnetic resonance imaging scans of 40,169 individuals in UK Biobank. We discovered 388 regional brain folding associations across 77 genetic loci, with genes in associated loci enriched for expression in the cerebral cortex, neuronal development processes, and differential regulation during early brain development. We integrated brain eQTLs to refine genes for various loci, implicated several genes involved in neurodevelopmental disorders, and highlighted global genetic correlations with neuropsychiatric phenotypes. We provide an interactive 3D visualisation of our summary associations, emphasising added resolution of regional analyses. Our results offer new insights into the genetic architecture of brain folding and provide a resource for future studies of sulcal morphology in health and disease.

Age and sex effects on advanced white matter microstructure measures in 15,628 older adults: A UK biobank study.

A comprehensive characterization of the brain's white matter is critical for improving our understanding of healthy and diseased aging. Here we used diffusion-weighted magnetic resonance imaging (dMRI) to estimate age and sex effects on white matter microstructure in a cross-sectional sample of 15,628 adults aged 45-80 years old (47.6% male, 52.4% female). Microstructure was assessed using the following four models: a conventional single-shell model, diffusion tensor imaging (DTI); a more advanced single-shell model, the tensor distribution function (TDF); an advanced multi-shell model, neurite orientation dispersion and density imaging (NODDI); and another advanced multi-shell model, mean apparent propagator MRI (MAPMRI). Age was modeled using a data-driven statistical approach, and normative centile curves were created to provide sex-stratified white matter reference charts. Participant age and sex substantially impacted many aspects of white matter microstructure across the brain, with the advanced dMRI models TDF and NODDI detecting such effects the most sensitively. These findings and the normative reference curves provide an important foundation for the study of healthy and diseased brain aging.