Multi-tracer PET and MR imaging visualize distinct metabolic and inflammatory profiles in the white matter of NMOSD and MOGAD.

Abstract

This study investigates distinct neuroinflammatory patterns in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) using multi-tracer PET and MR imaging. Eight NMOSD (5F/3M; median age 36.5) and six MOGAD patients (2F/4M; median age 34.0) underwent PET scans with [¹⁸F]FDG (glucose metabolism), the translocator protein (TSPO) ligand [¹⁸F]PBR06 (glial activation), and [¹¹C]acetate (astrocyte metabolism), integrated with synchronous 3T MRI sequences. Standardized uptake value ratios (SUVRs) referenced to contralateral white matter (WM) or whole brain were statistically compared across specific anatomic regions: active lesions, normal-appearing WM (NAWM), and periventricular zones. Both groups exhibited elevated [¹⁸F]PBR06 SUVR within lesions compared to contralateral WM, marking microgliosis. Crucially, NMOSD lesions showed significantly lower [¹⁸F]FDG SUVR (p ​= ​0.01; metabolic impairment) and [¹¹C]acetate SUVR (astrocyte dysfunction) than MOGAD lesions. Lesional [¹⁸F]PBR06 uptake correlated significantly with [¹⁸F]FDG uptake. Beyond lesions, NMOSD patients had higher [¹⁸F]FDG SUVR in cerebellar WM (p ​< ​0.01) and periventricular regions near the fourth ventricle (p ​= ​0.01), and higher [¹⁸F]PBR06 SUVR in cerebral WM (p ​= ​0.03), contrasted with MOGAD. With lesions in both disorders demonstrating microgliosis, NMOSD exhibited more severe lesion-specific metabolic suppression and astrocyte dysfunction, reflected in reduced [¹¹C]acetate uptake, coupled with regional inflammation (microgliosis) and hypermetabolism. These differential multi-tracer PET patterns, especially the combined reduction in lesional astrocytic ([¹¹C]acetate) and metabolic ([¹⁸F]FDG) markers in NMOSD versus MOGAD, highlight multimodal PET/MRI as a powerful tool for differentiating NMOSD and MOGAD pathophysiology.