Normative Cerebral Perfusion Across the Lifespan

TL;DR

This study presents the first comprehensive normative model of cerebral perfusion across the human lifespan, revealing developmental trajectories, sex differences, and disease-related abnormalities using a large multi-site dataset and advanced statistical modeling.

Contribution

It introduces a large-scale, detailed normative model of cerebral perfusion across all ages, incorporating sex differences and disease deviations, with implications for early diagnosis and understanding brain health.

Findings

Cerebral perfusion peaks at around 7.1 years of age.

Distinct regional maturation patterns between sexes.

Identification of disease-specific perfusion abnormalities.

Abstract

Cerebral perfusion plays a crucial role in maintaining brain function and is tightly coupled with neuronal activity. While previous studies have examined cerebral perfusion trajectories across development and aging, precise characterization of its lifespan dynamics has been limited by small sample sizes and methodological inconsistencies. In this study, we construct the first comprehensive normative model of cerebral perfusion across the human lifespan (birth to 85 years) using a large multi-site dataset of over 12,000 high-quality arterial spin labeling (ASL) MRI scans. Leveraging generalized additive models for location, scale, and shape (GAMLSS), we mapped nonlinear growth trajectories of cerebral perfusion at global, network, and regional levels. We observed a rapid postnatal increase in cerebral perfusion, peaking at approximately 7.1 years, followed by a gradual decline into adulthood. Sex differences were evident, with distinct regional maturation patterns rather than uniform differences across all brain regions. Beyond normative modeling, we quantified individual deviations from expected CBF patterns in neurodegenerative and psychiatric conditions, identifying disease-specific perfusion abnormalities across four brain disorders. Using longitudinal data, we established typical and atypical cerebral perfusion trajectories, highlighting the prognostic value of perfusion-based biomarkers for detecting disease progression. Our findings provide a robust normative framework for cerebral perfusion, facilitating precise characterization of brain health across the lifespan and enhancing the early identification of neurovascular dysfunction in clinical populations.