Mapping covariance in brain FDG uptake to structural connectivity

PURPOSE: Inter-subject covariance of regional 18F-fluorodeoxyglucose (FDG) PET measures (FDG(cov)) as proxy of brain connectivity has been gaining an increasing acceptance in the community. Yet, it is still unclear to what extent FDG(cov) is underlied by actual structural connectivity via white matter fiber tracts. In this study, we quantified the degree of spatial overlap between FDG(cov) and structural connectivity networks. METHODS: We retrospectively analyzed neuroimaging data from 303 subjects, both patients with suspected neurodegenerative disorders and healthy individuals. For each subject, structural magnetic resonance, diffusion tensor imaging, and FDG-PET data were available. The images were spatially normalized to a standard space and segmented into 62 anatomical regions using a probabilistic atlas. Sparse inverse covariance estimation was employed to estimate FDG(cov). Structural connectivity was measured by streamline tractography through fiber assignment by continuous tracking. RESULTS: For the whole brain, 55% of detected connections were found to be convergent, i.e., present in both FDG(cov) and structural networks. This metric for random networks was significantly lower, i.e., 12%. Convergent were 80% of intralobe connections and only 30% of interhemispheric interlobe connections. CONCLUSION: Structural connectivity via white matter fiber tracts is a relevant substrate of FDG(cov), underlying around a half of connections at the whole brain level. Short-range white matter tracts appear to be a major substrate of intralobe FDG(cov) connections. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05590-y.