Biophysics of BOLD fMRI investigated with animal models.

The widely-used BOLD fMRI signal depends on various anatomical, physiological, and imaging parameters. Thus, it is important to examine its biophysical and physiological source in order to optimize, model and accurately interpret fMRI. Animal models have been used to investigate these issues to take systematic measurements and combine with conventional invasive approaches. Here, we reviewed and discussed multiple issues, including the echo time-dependent intravascular contribution and extravascular contributions, gradient-echo vs. spin-echo fMRI, the physiological source of BOLD fMRI, arterial vs. venous cerebral blood volume change, cerebral oxygen consumption change, and arterial oxygen saturation change. We then discuss future directions of animal fMRI and translation to human fMRI. Systematic biophysical BOLD fMRI studies provide insight into the modeling and interpretation of BOLD fMRI in animals and humans.