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Zusammenfassung:
Mammalian brain function depends on the communication of various cell types and tissues via signaling molecules such as neurotransmitters. We develop a technology that applies functional magnetic resonance imaging (fMRI) and other hemodynamic imaging methods to visualize such signaling processes with spatiotemporal precision on a brain-wide scale in mammals. Hemodynamic imaging using fMRI and ultrasound represents the gold standard for visualizing whole-brain function in animals and humans, but lacks critical information on molecular pathways or signaling molecules underlying the measured imaging signals. We leverage the power of these approaches by engineering genetically-encoded probes that convert intra- and extracellular molecular signals into hemodynamic imaging contrast. Molecular hemodynamic imaging facilitates multi-modal and multi-scale detection of molecular brain function in living mammals. It provides a bridging technology between brain-wide functional imaging with fMRI and highly sensitive, molecular nuclear imaging. The approach complements spatiotemporally highly precise, but locally-confined fluorescence imaging to visualize brain-wide molecular signaling dynamics that shape healthy and pathological brain function.