Zero Echo Time Functional MRI in Humans: Technical Demonstration and Proof-of-Concept

Conventional EPI-based fMRI relies on the BOLD contrast to map activity changes, but is limited by high acoustic noise, susceptibility artifacts, and distortion near air-tissue interfaces. Ultra-short and zero-echo-time (ZTE) sequences have gained considerable attention in animal fMRI studies due to their robustness against susceptibility effects, low acoustic noise, and ability to capture signal sources distinct from those of conventional BOLD imaging. In this study, we present a feasibility-level proof-of-concept technical demonstration of ZTE-based fMRI in humans at 3T, while maintaining many of the advantages observed in preclinical studies. Phantom measurements demonstrate that the ZTE protocol is sensitive to oxygenation-related T₁ changes at 3T, supporting its feasibility for detecting related functional signals. In five healthy volunteers, task-based visual stimulation and finger tapping experiments elicited activation in primary visual and motor cortices, respectively, using the ZTE sequence, demonstrating proof-of-concept feasibility in this small cohort. Resting-state components with spatial patterns consistent with canonical visual and sensorimotor networks were identified using independent component analysis in the same cohort. Compared to BOLD-EPI, ZTE showed significantly reduced acoustic noise and was largely insensitive to susceptibility-induced signal loss in this feasibility study. While this work represents our initial experience using ZTE for human fMRI at 3T, the presented results will motivate future studies to refine and extend this approach to explore complementary functional contrast mechanisms.