Super-resolution sodium MRI of human gliomas at 3T using physics-based generative artificial intelligence

Sodium neuroimaging provides unique insights into the cellular and metabolic properties of brain tumors. However, at 3T, sodium neuroimaging MRI’s low signal-to-noise ratio (SNR) and resolution discourages routine clinical use. We evaluated the recently developed Anatomically constrained GAN using physics-based synthetic MRI artifacts” (ATHENA) for high-resolution sodium neuroimaging of brain tumors at 3T. We hypothesized the model would improve the image quality while preserving the inherent sodium information.

4,573 proton MRI scans from 1,390 suspected brain tumor patients were used for training. Sodium and proton MRI datasets from Twenty glioma patients were collected for validation. Twenty-four image-guided biopsies from seven patients were available for sodium-proton exchanger (NHE1) expression evaluation on immunohistochemistry. High-resolution synthetic sodium images were generated using the ATHENA model, then compared to native sodium MRI and NHE1 protein expression from image-guided biopsy samples.

The ATHENA produced synthetic-sodium MR with significantly improved SNR (native SNR 18.20 ± 7.04; synthetic SNR 23.83 ± 9.33, P = 0.0079). The synthetic-sodium values were consistent with the native measurements (P = 0.2058), with a strong linear correlation within contrast-enhancing areas of the tumor (R² = 0.7565, P = 0.0005), T2-hyperintense (R² = 0.7325, P < 0.0001), and necrotic areas (R² = 0.7678, P < 0.0001). The synthetic-sodium MR and the relative NHE1 expression from image-guided biopsies were better correlated for the synthetic (ρ = 0.3269, P < 0.0001) than the native (ρ = 0.1732, P = 0.0276) with higher sodium signal in samples expressing elevated NHE1 (P < 0.0001).

ATHENA generates high-resolution synthetic-sodium MRI at 3T, enabling clinically attainable multinuclear imaging for brain tumors that retain the inherent information from the native sodium. The resulting synthetic sodium significantly correlates with tissue expression, potentially supporting its utility as a non-invasive marker of underlying sodium homeostasis in brain tumors.