Shnitko Tatiana A, Walton Lindsay R, Peng Tong-Yu Rainey, Lee Sung-Ho, Chao Tzu-Hao Harry, Verber Matthew D, Wightman R Mark, Shih Yen-Yu Ian
Center for Animal MRI, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nat Protoc. 2025 Oct 8. doi: 10.1038/s41596-025-01250-9.
One of the challenges associated with functional magnetic resonance imaging (MRI) studies is integrating and causally linking complementary functional information, often obtained using different modalities. Achieving this integration requires synchronizing the spatiotemporal multimodal datasets without mutual interference. Here we present a protocol for integrating electrochemical measurements with functional MRI, enabling the simultaneous assessment of neurochemical dynamics and brain-wide activity. This Protocol addresses challenges such as artifact interference and hardware incompatibility by providing magnetic resonance-compatible electrode designs, synchronized data acquisition settings and detailed in vitro and in vivo procedures. Using dopamine as an example, the protocol demonstrates how to measure neurochemical signals with fast-scan cyclic voltammetry (FSCV) in a flow-cell setup or in vivo in rats during MRI scanning. These procedures are adaptable to various analytes measurable by FSCV or other electrochemical techniques, such as amperometry and aptamer-based sensing. By offering step-by-step guidance, this Protocol facilitates studies of neurovascular coupling with the neurochemical basis of large-scale brain networks in health and disease and could be adapted in clinical settings. The procedure requires expertise in MRI, FSCV and stereotaxic surgeries and can be completed in 7 days.