Single-Quantum Sodium MRI at 3T for the Separation of Mono- and Bi-T2 Sodium Signals

Sodium magnetic resonance imaging (MRI) is highly sensitive to cellular ionic balance due to tenfold difference in sodium concentration across membranes, actively maintained by the sodium-potassium (Na⁺-K⁺) pump. Disruptions in this pump or membrane integrity, as seen in neurological disorders like epilepsy, multiple sclerosis, bipolar disease, and mild traumatic brain injury, lead to increased intracellular sodium. However, this cellular-level alteration is often masked by the dominant extracellular sodium signal, making it challenging to distinguish sodium populations with mono- vs. bi-exponential transverse (T₂) decays - especially given the low signal-to-noise ratio (SNR) even at an advanced clinical field of 3 Tesla. Here, we propose a novel technique that leverages intrinsic difference in T₂ decays by acquiring single-quantum images at multiple echo times (TEs) and applying voxel-wise matrix inversion for accurate signal separation. Using numerical models, agar phantoms, and human subjects, we achieved high separation accuracy in phantoms (95.8% for mono-T₂ and 72.5-80.4% for bi-T₂) and demonstrated clinical feasibility in humans. This approach may enable early detection of neurological disorders and early assessment of treatment responses at the cellular level using sodium MRI at 3T.