From metabolic connectivity to molecular connectivity: application to dopaminergic pathways.

Abstract

This study aims to reveal the feasibility and potential of molecular connectivity based on neurotransmission in comparison with the metabolic connectivity with an application to dopaminergic pathways. For this purpose, we propose to compare the neurotransmission connectivity findings using ¹²³I-FP-CIT SPECT and ¹⁸F-FDOPA PET with the metabolic connectivity findings using ¹⁸F-FDG PET. ¹⁸F-FDG PET and ¹²³I-FP-CIT SPECT images from 47 subjects and ¹⁸F-FDOPA PET images from 177 subjects, who had no neurological or psychiatric disorders, were studied. Interregional correlation analyses were performed at the group level to determine the midbrain's connectivity via glucose metabolic rate using ¹⁸F-FDG PET and via dopaminergic binding potential using ¹²³I-FP-CIT SPECT and ¹⁸F-FDOPA PET. SPM-T maps of each radiotracer were generated, and masks used to highlight the significant differences obtained among the imaging modalities and targets. The three dopaminergic pathways (i.e., nigrostriatal, mesolimbic, and mesocortical) were identified by ¹⁸F-FDG PET (1599 voxels, with a T_max value of 12.6), ¹²³I-FP-CIT SPECT (1120 voxels, with T_max value of 5.1), and ¹⁸F-FDOPA PET (6054 voxels, with T_max value of 11.7) for a T voxel threshold of 5.10, 2.80, and 5.10, respectively. Using the same T voxel threshold of 5.10, ¹⁸F-FDOPA PET showed more specific findings than ¹⁸F-FDG PET with less voxels identified outside these pathways (- 9323 voxels), whereas no significant voxels were obtained with ¹²³I-FP-CIT SPECT at this threshold. The present study illustrates the feasibility and interest in using molecular connectivity with ¹⁸F-FDOPA PET for dopaminergic pathways. Such analyses could be applied to specific diseases involving the dopaminergic system.