Physiological basis for BOLD MR signal changes due to neuronal stimulation: separation of blood volume and magnetic susceptibility effects.

An NMR method is applied for separating blood volume and magnetic susceptibility effects in response to neuronal stimulation in a rat model. The method uses high susceptibility contrast agents to enhance blood volume induced signal changes. In the absence of exogenous agent, the dominant source of signal change on neuronal activation is associated with the signal increase from the blood oxygen level dependent (BOLD) effect. The relative negative contribution of blood volume changes to BOLD changes is maximally estimated to be 34%. The blood volume changes associated with median nerve stimulation (7 Hz) in the motor cortex are 26+/-7% and the corresponding blood susceptibility changes are 0.021+/-0.006 ppm. These methods can be applied to enhance the sensitivity of fMRI signal response and provide accurate quantitative measures of blood volume response to stimulation.