A novel method for PET connectomics guided by fibre-tracking MRI: Application to Alzheimer's disease

This study introduces a novel brain connectome matrix, track-weighted PET connectivity (twPC) matrix, which combines positron emission tomography (PET) and diffusion magnetic resonance imaging data to compute a PET-weighted connectome at the individual subject level. The new method is applied to characterise connectivity changes in the Alzheimer's disease (AD) continuum. The proposed twPC samples PET tracer uptake guided by the underlying white matter fibre-tracking streamline point-to-point connectivity calculated from diffusion MRI (dMRI). Using tau-PET, dMRI and T1-weighted MRI from the Alzheimer's Disease Neuroimaging Initiative database, structural connectivity (SC) and twPC matrices were computed and analysed using the network-based statistic (NBS) technique to examine topological alterations in early mild cognitive impairment (MCI), late MCI and AD participants. Correlation analysis was also performed to explore the coupling between SC and twPC. The NBS analysis revealed progressive topological alterations in both SC and twPC as cognitive decline progressed along the continuum. Compared to healthy controls, networks with decreased SC were identified in late MCI and AD, and networks with increased twPC were identified in early MCI, late MCI and AD. The altered network topologies were mostly different between twPC and SC, although with several common edges largely involving the bilateral hippocampus, fusiform gyrus and entorhinal cortex. Negative correlations were observed between twPC and SC across all subject groups, although displaying an overall reduction in the strength of anti-correlation with disease progression. twPC provides a new means for analysing subject-specific PET and MRI-derived information within a hybrid connectome using established network analysis methods, providing valuable insights into the relationship between structural connections and molecular distributions.Practitioner Points New method is proposed to compute patient-specific PET connectome guided by MRI fibre-tracking. Track-weighted PET connectivity (twPC) matrix allows to leverage PET and structural connectivity information. twPC was applied to dementia, to characterise the PET nework abnormalities in Alzheimer's disease and mild cognitive impairment. We have developed a novel track-weighted PET connectivity (twPC) that combines information from PET and diffusion MRI. The hybrid twPC enables analysis of subject-specific PET and MRI-derived information using network-based analysis, providing valuable insights into the relationship between structural connectivity and molecular tracer distributions in the Alzheimer's spectrum.double dagger image