MR-μScope: a multi-scale and simultaneous MRI-miniaturized microscopy system for elucidating neurovascular coupling

Blood Oxygen Level Dependent functional MRI (BOLD-fMRI) revolutionized non-invasive brain mapping, yet the physiological origins of its signal, linking microscopic neurovascular activity to macroscopic hemodynamics, remain elusive. To bridge this gap, we developed MR-μScope: a simultaneous and multimodal platform that integrates preclinic high-field MRI (9.4T) and miniaturized fluorescence microscopy (Miniscope). Our system contains an MR-compatible Miniscope with electromagnetic shielding, a customized radiofrequency coil with a central optical window, and an adjustable animal cradle, enabling artifact-free acquisition of whole-brain fMRI alongside microscopic vascular dynamics. Phantom validation confirmed negligible cross-modal interference (fMRI SNR ≥ 15 dB; optical SNR ≥ 26 dB). MR-μScope captured stimulus-evoked microvascular dilation and blood flow velocity changes in the somatosensory cortex concurrent with BOLD signals, revealing vessel-size-dependent neurovascular coupling. MR-μScope provides an effective solution for deciphering multi-scale neurovascular interactions and offers unique potential for advancing research into brain function and disease mechanisms involving vascular pathology.