Longitudinal assessment of early-life white matter development with quantitative relaxometry in nonhuman primates

Alterations in white matter (WM) development are associated with many neuropsychiatric and neurodevelop-mental disorders. Most MRI studies examining WM development employ diffusion tensor imaging (DTI), which relies on estimating diffusion patterns of water molecules as a reflection of WM microstructure. Quantitative relaxometry, an alternative method for characterizing WM microstructural changes, is based on molecular in-teractions associated with the magnetic relaxation of protons. In a longitudinal study of 34 infant non-human primates (NHP) (Macaca mulatta) across the first year of life, we implement a novel, high-resolution, T1-weighted MPnRAGE sequence to examine WM trajectories of the longitudinal relaxation rate (qR(1)) in relation to DTI metrics and gestational age at scan. To the best of our knowledge, this is the first study to assess developmental WM trajectories in NHPs using quantitative relaxometry and the first to directly compare DTI and relaxometry metrics during infancy. We demonstrate that qR(1) exhibits robust logarithmic growth, unfolding in a posterior-anterior and medial-lateral fashion, similar to DTI metrics. On a within-subject level, DTI metrics and qR(1) are highly cor-related, but are largely unrelated on a between-subject level. Unlike DTI metrics, gestational age at birth (time in utero ) is a strong predictor of early postnatal qR(1) levels. Whereas individual differences in DTI metrics are maintained across the first year of life, this is not the case for qR(1). These results point to the similarities and dif-ferences in using quantitative relaxometry and DTI in developmental studies, providing a basis for future studies to characterize the unique processes that these measures reflect at the cellular and molecular level.

Automated summary

Alterations in white matter development are related to neuropsychiatric disorders. Quantitative relaxometry can be used to evaluate white matter microstructural changes. A study on infant non-human primates found correlations between quantitative relaxometry and diffusion tensor imaging metrics, with gestational age being a stronger predictor for relaxometry metrics. This provides a basis for future studies.