A great challenge in neuroscience is the development of minimally invasive direct readouts of neural activity. Molecular functional magnetic resonance imaging (molecular fMRI) is a technology that can bridge this divide by providing avenues for mapping microscopic activity throughout the living brain. Such a technique combines the whole brain coverage of blood oxygenation level dependent (BOLD) imaging, the current gold standard in fMRI, with the molecular specificity and direct measurements afforded by optical probes. By designing agents whose MR signal is responsive to endogenous molecules involved in neuronal signaling, we can progress towards highly spatiotemporally-resolved measurements of a broad range neural phenomena. Here, recent in vitro advances in our development of chemical and biological tools for molecular fMRI will be presented. This development primarily involves the design of lanthanide(III)-binding metalloproteins that are capable of reporting on the binding of neurotransmitters (e.g. dopamine) through multiple modalities. The paramagnetic metal center at the core of the modified protein is key to providing the response, with lanthanide(III) ions providing advantages over other ions both in terms of available MR relaxivity changes and in potential sensing readouts. By changing the lanthanide(III) ion, the signaling modality can be switched from T1/ T2-weighted MRI, to chemical exchange saturation transfer (CEST), and/or luminescence. Future strategies are focused towards enhancing the selectivity and overall response of these metalloprotein-based molecular fMRI sensors.

Lanthanide(III)-binding proteins as sensors for molecular fMRI

256th National Meeting (2018)

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