Automated microfluidic hyperpolarization reactor for neurometabolic imaging

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Abstract Brain function is regulated by molecular signaling and metabolism, however, our ability to track neurometabolic transformations deep in the brain is very underdeveloped compared to the central role of neurometabolism in neurodegenerative disease or brain function in general. In this Phase I SBIR, it is our goal to establish and refine emergent hyperpolarization technology as an inexpensive, sturdy and reliable neurometabolic imaging tool that can be disseminated and applied broadly. Current molecular imaging approaches, for example PET/SPECT, require an immense infrastructure and are not broadly applicable. In this proposal we will produce, test and refine two hyperpolarization units that allow for molecular imaging at low cost at any research facility. Specifically, the hyperpolarizers deliver safe, injectable solutions of endogenous metabolites that carry hyperpolarized nuclear spins, which are detected using any MRI system. The hyperpolarization enhances the MRI signals by 4 to 7 orders of magnitude and reports directly on the molecular transformations in study subjects. Hence direct imaging of molecular pathways in the living subject is enabled. The objective of this proposal is to make existing hyperpolarizer prototypes sturdy and easy to use. Simultaneously, we aim for pilot installations at pre-clinical sites in order to test the prototype’s ability to integrate with pre-clinical workflows. With successful completion this Phase I SBIR we will have a sturdy and easy-to-use hyperpolarizer that makes hyperpolarized MRI accessible to the neuroscience research community and enables non-invasive imaging of metabolic dysregulation during the earliest stages of disease. In turn the established devices and workflow lead to new insights into molecular pathology and to preclinical testing of novel interventions and drugs.