7T 3D-MR Spectroscopic Imaging of GSH and GPX4 Immunohistochemistry Staining Reveal Oxidative Stress Patterns in MS Lesions

Motivation: GSH in MS can reveal oxidative stress areas where the body mounts defence, but the mechanism of GSH counteraction remains poorly understood due to limitations of standard MRS. Goal(s): By mapping GSH distribution across lesion types, we aim to elucidate antioxidative responses in the MS brain, informing potential therapeutic targets. Approach: We used 7T high-resolution echo-less 3D-MRSI to map GSH levels in 22 MS patients and validated findings with GPX4 immunohistochemistry post mortem. Results: The GSH/tCr ratio was elevated in lesions, particularly paramagnetic rim lesions, compared to normal-appearing WM; GPX4 staining indicated higher antioxidative activity in lesions than in normal-appearing and healthy WM. Impact: High-resolution 7T 3D-MRSI mapping of GSH reveals oxidative stress patterns across MS lesions, enhancing in vivo lesion monitoring and offering comprehensive insights that support clinical management and progression tracking in multiple sclerosis.