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

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Lui, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5456028/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted 8 You are reading this latest preprint version Abstract 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 (T 2 ) 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 T 2 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-T 2 and 72.5–80.4% for bi-T 2 ) 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. Biological sciences/Neuroscience/Diseases of the nervous system Biological sciences/Neuroscience/Diseases of the nervous system/Bipolar disorder Biological sciences/Neuroscience/Diseases of the nervous system/Epilepsy Biological sciences/Neuroscience/Diseases of the nervous system/Multiple sclerosis Biological sciences/Neuroscience/Diseases of the nervous system/Neurodegeneration Health sciences/Medical research/Translational research Full Text Additional Declarations Competing interest reported. Authors YQ and FEB are inventor of a US Patent Application, No.: 18/920,506. Filed on October 18, 2024. The other authors have no competing interest. Supplementary Files NaSepMoBiSIR1.pdf Cite Share Download PDF Status: Published Journal Publication published 28 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 13 May, 2025 Reviews received at journal 08 May, 2025 Reviews received at journal 15 Apr, 2025 Reviewers agreed at journal 15 Apr, 2025 Reviewers agreed at journal 05 Apr, 2025 Reviewers invited by journal 04 Apr, 2025 Submission checks completed at journal 01 Apr, 2025 First submitted to journal 19 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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