Modeling of vascular space occupancy and BOLD functional MRI from first principles using real microvascular angiograms

PURPOSE The vascular space occupancy (VASO) is a functional MRI technique for probing cerebral blood volume changes noninvasively, including during neuronal activation in humans. An important consideration when implementing VASO is the BOLD effect in the signal. Assessing the physical origin of this BOLD contamination and the capabilities of correction methods could improve the quantification of cerebral blood volume changes with VASO. METHODS Given the heterogeneity of cerebral microvascular architecture, the vascular geometry within an MRI voxel can influence both BOLD and VASO signals. To investigate this effect, 3D high-resolution images of mouse cerebral vasculature measured with two-photon microscopy were used to model BOLD and VASO signals from first principles using Monte Carlo diffusion of water protons. Quantitative plots of VASO together with intravascular and extravascular BOLD signals as a function of TE at B0 fields 1.5 T to 14 T were obtained. RESULTS The BOLD contamination of the VASO response was on the order of 50% for gradient echo and 5% for spin echo at 7 T and TE = 6 ms and significantly increased with TE and B0 . Two currently used correction schemes were shown to account for most of this contamination and recover accurate relative signal changes, with optimal correction obtained using TEs as short as possible. CONCLUSION These results may provide useful information for optimizing sequence parameters in VASO and BOLD functional MRI, leading the way to a wider application of these techniques in healthy and diseased brain.