Linking neuron-axon-synapse architecture to white matter vasculature using high-resolution multimodal MRI in primate brain

Blood vessels and axons align outside the brain due to shared growth factors. However, this neuron-axon-synapse and vessel relationship within the brain white matter remains unclear, primarily due to the technical challenges of charting the complex trajectories of fiber tracts and the dense network of arteries. Consequently, the organizational logic and neurometabolic factors shaping white matter vasculature remain poorly understood. Here, we address these questions using high-resolution multimodal MRI, in vitro neuron density, and receptor autoradiography in macaque monkeys. In superficial white matter, vascularity exhibited parallel alignment with the cortical surface. This vascularity showed negligible dependence on overlying gray matter neuron density (R2 = 0.01), minimal dependence on white matter myelination (R2 = 0.10), and moderate correlation with receptor density (R2 = 0.27). These suggest an association of vascularity with energy demands and axonal branching. In deep white matter, axon geometry, density, and proximity to the cortical surface predict vascular volume with high precision (R2 = 0.62). Overall, these findings establish a relation between neuron-axon-synapse architecture and white matter vasculature in the primate brain, offering advances in understanding the organization and pathophysiology of white matter.