Harnessing the Power of Advanced Fetal Neuroimaging to Understand In Utero Footprints for Later Neuropsychiatric Disorders

Adverse intrauterine events may profoundly impact fetal risk for future adult diseases. The mechanisms underlying this increased vulnerability are complex and remain poorly understood. Contemporary advances in fetal magnetic resonance imaging (MRI) have provided clinicians and scientists with unprecedented access to in vivo human fetal brain development to begin to identify emerging endophenotypes of neuropsychiatric disorders such as autism spectrum disorder, attention-deficit/hyperactivity disorder, and schizophrenia. In this review, we discuss salient findings of normal fetal neurodevelopment from studies using advanced, multimodal MRI that have provided unparalleled characterization of in utero prenatal brain morphology, metabolism, microstructure, and functional connectivity. We appraise the clinical utility of these normative data in identifying high-risk fetuses before birth. We highlight available studies that have investigated the predictive validity of advanced prenatal brain MRI findings and long-term neurodevelopmental outcomes. We then discuss how ex utero quantitative MRI findings can inform in utero investigations toward the pursuit of early biomarkers of risk. Lastly, we explore future opportunities to advance our understanding of the prenatal origins of neuropsychiatric disorders using precision fetal imaging.