Integrated imaging of [11C]-PBR28 PET, MR diffusion and magnetic resonance spectroscopy 1H-MRS in amyotrophic lateral sclerosis

Objective: To determine the relationship between brain tissue metabolites measured by in vivo magnetic resonance spectroscopy (1H-MRS), and glial activation assessed with [11C]-PBR28 uptake in people with amyotrophic lateral sclerosis (ALS). Methods: Forty ALS participants were evaluated clinically using the revised ALS functional rating scale (ALSFRS-R) and upper motor neuron burden (UMNB). All participants underwent simultaneous brain [11C]-PBR28 PET and MR imaging including diffusion tensor imaging to acquire fractional anisotropy (FA). [11C]-PBR28 uptake was measured as standardized uptake values normalized by whole brain mean (SUVR). 1H-MRS metabolite ratios (myo-inositol/creatine, mI/Cr; N-acetylaspartate/creatine, NAA/Cr) were measured within the precentral gyri and brain stem (regions known to be involved in ALS pathophysiology), and precuneus (which served as a control region). Whole brain voxel-wise correlation analyses were employed to identify brain regions exhibiting an association between metabolites within the VOIs and [11C]-PBR28 uptake. Results: In the precentral gyri, [11C]-PBR28 uptake correlated positively with mI/Cr and negatively with NAA/Cr. The same correlations were not statistically significant in the brain stem, or in the control precuneus region. Whole brain voxel-wise correlation analyses between the estimated brain metabolites within the VOIs and SUVR were highly correlated in the precentral gyri. Decreased FA values in the precentral gyri were correlated with reduced NAA/Cr and elevated mI/Cr. Higher UMNB was correlated with increased [11C]-PBR28 uptake and mI/Cr, and decreased NAA/Cr. ALSFRS-R total score correlated positively with NAA/Cr and negatively with mI/Cr. Conclusion: Integrated PET-MR and 1H-MRS imaging demonstrates associations between markers for neuronal integrity and neuroinflammation and may provide valuable insights into disease mechanisms in ALS. Keywords: 1H-MRS, PET, Glial activation, Amyotrophic lateral sclerosis, [11C]-PBR28, DT