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bioRxiv · 10.64898/2026.04.01.715894

High-Field Multinuclear MRI Reveals Sodium Relaxation Heterogeneity in Cortical Organoids

Yu, G.·Liu, X.·Hike, D.·Qian, C.·Devor, A.·Zeldich, E.·Thunemann, M.·Zhou, X. A.
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Abstract

Sodium magnetic resonance imaging (23Na MRI) provides a unique opportunity to probe ionic microenvironments in neural tissue because sodium ions play central roles in membrane electrophysiology, ion transport, and cellular homeostasis. Unlike conventional proton ({superscript 1}H) MRI, which primarily reflects water distribution and tissue structure, {superscript 2}3Na MRI is sensitive to ionic compartmentation and quadrupolar interactions arising from the spin-3/2 nature of the sodium nucleus. However, sodium MRI remains technically challenging due to intrinsically low signal sensitivity and rapid biexponential relaxation, particularly when imaging small biological systems. Here, we establish a high-field multinuclear MRI platform for imaging human cerebral organoids at 14 Tesla. Cerebral organoids derived from human induced pluripotent stem cells provide a simplified three-dimensional neural tissue model that enables investigation of ionic microenvironments without vascular or systemic confounds. Using a dual-tuned {superscript 1}H/{superscript 2}3Na radiofrequency coil, we performed co-registered structural, diffusion, and sodium imaging of individual fixed organoids. High-resolution {superscript 1}H MRI (33-100 m) revealed pronounced microstructural heterogeneity, while multi-echo {superscript 2}3Na MRI (300-400 m) enabled voxel-wise characterization of quadrupolar relaxation behavior. Bi-exponential analysis of the sodium signal decay identified distinct relaxation components (T2*short {approx} 1 ms and T2*long {approx} 12 ms) and revealed spatial heterogeneity in sodium microenvironments across the organoid tissue. These results demonstrate the feasibility of quantitative sodium relaxometry in cortical organoids and establish a multinuclear imaging platform for investigating ionic microenvironment dynamics in three-dimensional neural tissue models.

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Yu, G., Liu, X., Hike, D., Qian, C., Devor, A., Zeldich, E., Thunemann, M., Zhou, X. A.. 2026-04-05. High-Field Multinuclear MRI Reveals Sodium Relaxation Heterogeneity in Cortical Organoids. https://doi.org/10.64898/2026.04.01.715894

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