Addressing artifactual bias in large, automated MRI analyses of brain development

Large, population-based magnetic resonance imaging (MRI) studies of adolescents promise transformational insights into neurodevelopment and mental illness risk. However, youth MRI studies are especially susceptible to motion and other artifacts that introduce non-random noise. After visual quality control of 11,263 T1 MRI scans obtained at age 9-10 years through the Adolescent Brain Cognitive Development study, we uncovered bias in measurements of cortical thickness and surface area in 55.1% of the samples with suboptimal image quality. These biases impacted analyses relating structural MRI and clinical measures, resulting in both false-positive and false-negative associations. Surface hole number, an automated index of topological complexity, reproducibly identified lower-quality scans with good specificity, and its inclusion as a covariate partially mitigated quality-related bias. Closer examination of high-quality scans revealed additional topological errors introduced during image preprocessing. Correction with manual edits reproducibly altered thickness measurements and strengthened age-thickness associations. We demonstrate here that inadequate quality control undermines advantages of large sample size to detect meaningful associations. These biases can be mitigated through additional automated and manual interventions.