SORDINO: silent, sensitive, specific and artifact-resistant fMRI in awake, behaving mice

Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has advanced brain mapping across species. This widely used technique, however, faces challenges such as acoustic noise, electromagnetic interference, motion artifacts, magnetic-field inhomogeneity and limitations in sensitivity and specificity. Here we introduce Steady-state On-the-Ramp Detection of INduction-decay with Oversampling (SORDINO), an improved zero echo time (ZTE)-based fMRI technique that maintains ultra-low slew rate and acquires data exclusively during gradient direction changes. At 9.4 T, SORDINO outperforms conventional gradient-recalled-echo-based echo-planar imaging and ZTE in metrics crucial for fMRI while being silent, sensitive, specific and resistant to motion and susceptibility artifacts. We showcase SORDINO's superior compatibility with multimodal experiments and reveal T₁-based contrast mechanisms distinct from BOLD that are expected to generalize across ZTE-based fMRI techniques. We further demonstrate SORDINO brain-wide activity and functional connectivity mapping in awake, behaving mice, overcoming stress-related, motion-related and sensitivity-related limitations that remain common barriers in current animal fMRI studies.