Neuronal-Activity-Related Sodium (NARS) fMRI Reveals Millisecond Neuronal Dynamics Beyond Hemodynamic Readouts

Area of Science:

• Neuroimaging
• Magnetic Resonance Imaging (MRI)
• Neuroscience

Background:

• Current noninvasive neuroimaging methods lack millisecond resolution for direct neuronal activity mapping.
• Hemodynamic fMRI (¹H-based) has temporal and spatial limitations due to its vascular origin, especially when neurovascular coupling is altered in disease.

Purpose of the Study:

• To develop an ultrafast ²³Na fMRI platform for direct, millisecond-timescale neuronal activity mapping.
• To establish neural activity-related sodium (NARS) fMRI as a viable neuroimaging technique.

Main Methods:

• Developed an ultrafast ²³Na fMRI system at 14 T utilizing a reshuffled k-t 3D gradient echo readout (TR/TE, 10ms/1ms).
• Integrated an implantable RF coil and respiration-gated acquisition for enhanced sampling rate and SNR.
• Validated the method in rats and mice using somatosensory forepaw stimulation and simultaneous iGluSnFR glutamate fiber photometry.

Main Results:

• Demonstrated a localized ~2-3% ²³Na signal decrease in the forepaw-somatosensory cortex (FP-S1) within 10-30 ms post-stimulation.
• Observed that the NARS signal pattern correlated well with conventional BOLD-fMRI maps.
• Found that larger evoked glutamate transients coincided with larger NARS decreases, supporting a neuronal origin.

Conclusions:

• Neural activity-related sodium (NARS) fMRI successfully maps neuronal activity at millisecond resolution.
• The observed negative NARS response is attributed to activity-dependent sodium ion redistribution.
• NARS fMRI offers a promising new tool for direct, mesoscale neuronal mapping in neuroscience research.