Hyperpolarized ¹³C-bicarbonate production correlates with excitatory neuron distribution in the human brain

Whole-brain metabolic topography measured with hyperpolarized ¹³C-pyruvate MRI in 40 healthy individuals was correlated with microarray transcriptomic data from the Allen Human Brain Atlas. Spatial autocorrelation was addressed using both model-based and non-model-based methods, and two parcellation atlases with different numbers of regions were employed to reduce the likelihood of false positives. Brain regions with higher expression of transcripts characteristic of excitatory neurons showed an elevated bicarbonate-to-pyruvate ratio, indicating a higher flux through pyruvate dehydrogenase. Specifically, the Ex2 and Ex4 excitatory neuron subtypes showed the strongest enrichment among all cell-type gene sets. Collectively, these findings connect regional variations in metabolic neuroimaging profiles to underlying patterns of cellular gene expression, offering a framework for understanding the molecular basis of tissue-level metabolic organization.