The metabolic and hemodynamic dependencies of the blood oxygenation level-dependent (BOLD) signal form the basis for calibrated fMRI, where the focus is on oxidative energy demanded by neural activity. An important part of calibrated fMRI is the power-law relationship between the BOLD signal and the deoxyhemoglobin concentration, which in turn is related to the ratio between oxidative demand (CMRO2) and blood flow (CBF). The power-law dependence between BOLD signal and deoxyhemoglobin concentration is signified by a scaling exponent β. Until recently most studies assumed a β value of 1.5, which is based on numerical simulations of the extravascular BOLD component. Since the basal value of CMRO2 and CBF can vary from subject-to-subject and/or region-to-region, a method to independently measure β in vivo should improve the accuracy of calibrated fMRI results. We describe a new method for β mapping through characterizing R2' - the most sensitive relaxation component of BOLD signal (i.e., the reversible magnetic susceptibility component that is predominantly of extravascular origin at high magnetic field) - as a function of intravascular magnetic susceptibility induced by an FDA-approved superparamagnetic contrast agent. In α-chloralose anesthetized rat brain, at 9.4 T, we measured β values of ~0.8 uniformly across large neocortical swathes, with lower magnitude and more heterogeneity in subcortical areas. Comparison of β maps in rats anesthetized with medetomidine and α-chloralose revealed that β is independent of neural activity levels at these resting states. We anticipate that this method for β mapping can help facilitate calibrated fMRI for clinical studies.

Calibrated fMRI extracts changes in oxidative energy demanded by neural activity based on hemodynamic and metabolic dependencies of the blood oxygenation level-dependent (BOLD) response. This procedure requires the parameter M, which is determined from the dynamic range of the BOLD signal between deoxyhemoglobin (paramagnetic) and oxyhemoglobin (diamagnetic). Since it is unclear if the range of M-values in human calibrated fMRI is due to regional/state differences, we conducted a 9.4T study to measure M-values across brain regions in deep (α-chloralose) and light (medetomidine) anesthetized rats, as verified by electrophysiology. Because BOLD signal is captured differentially by gradient-echo (R2*) and spin-echo (R2) relaxation rates, we measured M-values by the product of the fMRI echo time and R2' (i.e., the reversible magnetic susceptibility component), which is given by the absolute difference between R2* and R2. While R2' mapping was shown to be dependent on the k-space sampling method used, at nominal spatial resolutions achieved at high magnetic field of 9.4T the M-values were quite homogenous across cortical gray matter. However cortical M-values varied in relation to neural activity between brain states. The findings from this study could improve precision of future calibrated fMRI studies by focusing on the global uniformity of M-values in gray matter across different resting activity levels.