11C-acetate PET imaging in patients with multiple sclerosis

Abstract

Background: Activation of glial cells is a cardinal feature in multiple sclerosis (MS) pathology, and acetate has been reported to be selectively uptaken by astrocytes in the CNS. The aim of this study was to investigate the efficacy of PET with (11)C-acetate for MS diagnosis.

Materials and methods: Six patients with relapsing-remitting MS and 6 healthy volunteers (HV) were enrolled. The (11)C-acetate brain uptake on PET was measured in patients with MS and HV. Volume-of-interest analysis of cerebral gray and white matter based on the segmentation technique for co-registered MRI and voxel-based statistical parametric analysis were performed. Correlation between 11C-acetate uptake and the lesion number in T1- and T2- weighted MR images were also assessed.

Results: The standardized uptake value (SUV) of 11C-acetate was increased in both white and gray matter in MS patients compared to HV. Voxel-based statistical analysis revealed a significantly increased SUV relative to that in the bilateral thalami (SUVt) in a broad area of white matter, particularly in the subcortical white matter of MS patients. The numbers of T2 lesions and T1 black holes were significantly correlated with SUV of (11)C-acetate in white and gray matter.

Conclusions: The 11C-acetate uptake significantly increased in MS patients and correlated to the number of MRI lesions. These preliminary data suggest that (11)C-acetate PET can be a useful clinical examination for MS patients.

Figure 1. ¹¹C-acetate CNS biodistribution.

(A)Mean standardized uptake value (SUV) of each lesion. (B) Relative SUV compared to that of the thalamus (SUVt). Data are expressed as the mean ± standard error of the mean (SEM) (n = 6). The Mann–Whitney U test showed a significant difference in the median between the HV and MS groups (*:p<0.0055 after Bonferroni correction). HV  =  healthy volunteers, MS  =  multiple sclerosis.

Figure 2. ¹¹C-acetate uptake distribution and quantification in MS patients.

(A)Spatially normalized group mean images of ¹¹C-acetate SUVt automatically segmented based on MRI. VOI analysis summarizing the mean SUVt in WM (B) and GM (C), and the WM/GM SUV ratio (D) in the HV and MS groups. The identical analysis performed using spill-in-free VOIs are also shown (E–G). The p-value was calculated using the analysis of covariance to adjust the variance of age. (H) The SPM analysis result is overlaid onto the T1-weighted brain MRI template. Colored voxels indicate T-scores representing significantly increased ¹¹C-acetate uptake (SUVt) in patients with MS compared to HV patients. The spatially normalized PET images were smoothed for the analysis using a 12-mm FWHM isotropic Gaussian kernel. The significance thresholds are corrected for multiple comparisons at the cluster level with a p-value of 0.05 (family-wise error correction). SUV: standardized uptake value.

Figure 3. Correlation between ¹¹C-acetate SUV and the number of MRI lesions in patients with MS.

Correlation between ¹¹C-acetate SUV in WM or GM and the number of T1 black holes (A, C) or T2 lesions (B, D) in each hemisphere of the six MS patients. SUV: standardized uptake value.