Neuromark PET: A multivariate method for estimating whole brain fMRI guided intrinsic networks and connectomes from fMRI and PET data.

Positron emission tomography (PET) and magnetic resonance imaging (MRI) are both widely used neuroimaging techniques to study brain functional and molecular connectivity. Although whole brain resting functional MRI (fMRI) connectomes (a matrix describing the inter-regional connectivity patterns) are widely used, the integration or association of whole brain molecular connectomes with PET data are rarely done. This likely stems from the fact that PET data is typically analyzed by using a region of interest approach, while whole brain spatial networks and their connectivity (covariation) receive much less attention. As a result, to date, there have been little focus on directly comparing whole brain PET and fMRI connectomes. In this study, we present a method that uses spatially constrained independent component analysis (scICA) (utilizing fMRI components as spatial priors) to estimate corresponding (Amyloid) PET and fMRI connectomes and examine the relationship between them using datasets that include individuals with mild cognitive impairment (MCI). Our results demonstrate highly modularized PET connectome patterns that complement those identified from resting fMRI. In particular, fMRI showed strong intra-domain connectivity with interdomain anticorrelation in sensorimotor and visual domains as well as default mode network. PET amyloid data showed similar strong intra-domain effects, but showed much higher correlations within cognitive control and default mode domains, as well as anticorrelation between cerebellum and other domains. The estimated fMRI informed PET networks have similar, but not identical, network spatial patterns to the resting fMRI networks, with the fMRI informed PET networks being slightly smoother and, in some cases, showing variations in subnodes. To further compare the two modalities, we also analyzed the differences between individuals with MCI receiving medication versus a placebo. Results show both common and modality specific treatment effects on fMRI and PET connectomes. From our fMRI analysis, we observed higher connectivity differences in various regions, such as the connection between the thalamus and middle occipital gyrus, as well as the insula and right middle occipital gyrus. Meanwhile, the PET analysis revealed increased activation between the anterior cingulate cortex and the left inferior parietal lobe, along with other regions, in individuals who received medication versus placebo. In sum, our novel approach identifies corresponding whole-brain fMRI informed PET and fMRI networks and connectomes. While we observed common patterns of network connectivity, our analysis of the MCI treatment and placebo groups revealed that each modality captures modality and group specific information about brain networks, highlighting differences between the two groups in both network expression and network connectivity.