Direct imaging of macrovascular and microvascular contributions to BOLD fMRI in layers IV-V of the rat whisker-barrel cortex

The spatiotemporal characteristics of the hemodynamic response to increased neural activity were investigated at the level of individual intracortical vessels using BOLD-fMRI in a well-established rodent model of somatosensory stimulation at 11.7 T. Functional maps of the rat barrel cortex were obtained at 150 × 150 × 500 μm spatial resolution every 200 ms. The high spatial resolution allowed separation of active voxels into those containing intracortical macro vessels, mainly vein/venules (referred to as macrovasculature), and those enriched with arteries/capillaries and small venules (referred to as microvasculature) since the macro vessel can be readily mapped due to the fast T2 decay of blood at 11.7 T. The earliest BOLD response was observed within layers IV-V by 0.8s following stimulation and encompassed mainly the voxels containing the microvasculature and some confined macrovasculature voxels. By 1.2s, the BOLD signal propagated to the macrovasculature voxels where the peak BOLD signal was 2-3 times higher than that of the microvasculature voxels. The BOLD response propagated in individual venules/veins far from neuronal sources at later times. This was also observed in layers IV-V of the barrel cortex after specific stimulation of separated whisker rows. These results directly visualized that the earliest hemodynamic changes to increased neural activity occur mainly in the microvasculature and spread toward the macrovasculature. However, at peak response, the BOLD signal is dominated by penetrating venules even at layers IV-V of the cortex.