Brain function is regulated by molecular signaling and metabolism, however, our ability to track neurometabolictransformations deep in the brain is very underdeveloped compared to the central role of neurometabolism inneurodegenerative disease or brain function in general. In this Phase I SBIR, it is our goal to establish and refineemergent hyperpolarization technology as an inexpensive, sturdy and reliable neurometabolic imaging tool thatcan be disseminated and applied broadly. Current molecular imaging approaches, for example PET/SPECT, require an immense infrastructure andare not broadly applicable. In this proposal we will produce, test and refine two hyperpolarization units that allowfor molecular imaging at low cost at any research facility. Specifically, the hyperpolarizers deliver safe, injectablesolutions of endogenous metabolites that carry hyperpolarized nuclear spins, which are detected using any MRIsystem. The hyperpolarization enhances the MRI signals by 4 to 7 orders of magnitude and reports directly onthe molecular transformations in study subjects. Hence direct imaging of molecular pathways in the living subjectis 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 integratewith pre-clinical workflows. With successful completion this Phase I SBIR we will have a sturdy and easy-to-usehyperpolarizer that makes hyperpolarized MRI accessible to the neuroscience research community and enablesnon-invasive imaging of metabolic dysregulation during the earliest stages of disease. In turn the establisheddevices and workflow lead to new insights into molecular pathology and to preclinical testing of novelinterventions and drugs.
Public Health Relevance Statement: Project Narrative / Public Health Statement
In this Phase I SBIR, we develop and mature metabolic imaging technology that enables non-invasive detection
of early molecular pathophysiology, well before anatomical and physiological correlates are measurable. This
is a significant innovation because neurometabolic disturbances typically precede disease symptoms. Current
state-of-the-art technologies -- direct examination of brain tissue and molecular imaging -- are problematic and
very costly. In contrast, with the imaging approach proposed here, neurometabolic dysregulation can be detected
non-invasively and well before physiological effects become apparent. Our approach provides the neuroscience
research community (and beyond) a non-invasive imaging modality to probe neurometabolic disturbances and
is expected to lead to novel scientific insights as well as new diagnostics and interventions.
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