The blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) method, which is sensitive to vascular paramagnetic deoxyhemoglobin, is dependent on regional values of cerebral metabolic rate of oxygen utilization (CMRO2), blood flow (CBF), and volume (CBV). Induced changes in deoxyhemoglobin function as an endogenous contrast agent, which in turn affects the transverse relaxation rates of tissue water that can be measured by gradient-echo and spin-echo sequences in BOLD fMRI. The purpose here was to define the quantitative relation between BOLD signal change and underlying physiologic parameters. To this end, magnetic resonance imaging and spectroscopy methods were used to measure CBF, CMRO2, CBV, and relaxation rates (with gradient-echo and spin-echo sequences) at 7 Tesla in rat sensorimotor cortex, where cerebral activity was altered pharmacologically within the autoregulatory range. The changes in tissue transverse relaxation rates were negatively and linearly correlated with changes in CBF, CMRO2, and CBV. The multiparametric measurements revealed that CBF and CMRO2 are the dominant physiologic parameters that modulate the BOLD fMRI signal, where the ratios of (ΔCMRO2/CMRO2)/(ΔCBF/CBF) and (ΔCBV/CBV)/(ΔCBF/CBF) were 0.86 ± 0.02 and 0.03 ± 0.02, respectively. The calibrated BOLD signals (spatial resolution of 48 μL) from gradient-echo and spin-echo sequences were used to predict changes in CMRO2 using measured changes in CBF, CBV, and transverse relaxation rates. The excellent agreement between measured and predicted values for changes in CMRO2 provides experimental support of the current theory of the BOLD phenomenon. In gradient-echo sequences, BOLD contrast is affected by reversible processes such as static inhomogeneities and slow diffusion, whereas in spin-echo sequences these effects are refocused and are mainly altered by extravascular spin diffusion. This study provides steps by which multiparametric MRI measurements can be used to obtain high-spatial resolution CMRO2 maps.
High-Resolution CMRO2 Mapping in Rat Cortex: A Multiparametric Approach to Calibration of BOLD Image Contrast at 7 Tesla