Multimodal PET/MR imaging of prolonged disorders of consciousness: a pilot feasibility study

Background: Prolonged disorders of consciousness (pDOC), including vegetative/unresponsive wakefulness state (VS/UWS) and minimally conscious state (MCS), pose significant diagnostic and prognostic challenges. Multimodal neuroimaging has emerged as a promising tool to uncover neural biomarkers that reflect residual brain function and guide management. This pilot feasibility study aimed to preliminarily characterize metabolic, functional, and structural brain alterations in pDOC patients using simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging, and to examine their tentative associations with clinical behavioral responsiveness. Methods: Eight pDOC patients and eight matched healthy controls underwent hybrid 18F-FDG PET/MR scanning. Resting-state fMRI, diffusion tensor imaging (DTI), and FDG-PET were processed to assess amplitude of low-frequency fluctuations (ALFF), fractional anisotropy (FA), and glucose metabolism, respectively. Group differences were analyzed, and correlations with Coma Recovery Scale-Revised (CRS-R) scores were evaluated. Multimodal integration was performed across imaging modalities. Results: Compared to controls, pDOC patients exhibited reduced ALFF and FDG uptake in the posterior cingulate cortex (PCC) and anterior cingulate cortex (ACC), with exploratory increased ALFF in the visual cortex inversely correlated with visual responsiveness. Functional connectivity analyses revealed attenuated intra- and inter-network connectivity in the DMN, SN, and DAN. FDG-PET identified metabolic hypofunction in the insula, frontal cortex, and cerebellum, while DTI demonstrated widespread white matter FA reductions. Multimodal correspondence revealed partially overlapping abnormalities in the PCC and occipital regions, highlighting candidate hubs that may be relevant to consciousness level and warrant further validation. Conclusion: Simultaneous FDG-PET/MR was feasible in this pilot pDOC cohort and provided a convergent, multimodal assessment of metabolic-functional-structural alterations. The PCC and occipital visual cortices emerge as key regions linked to consciousness levels. Given the small sample size and cross-sectional design, these findings are preliminary, and warrant validation in larger longitudinal cohorts before clinical translation.