In vivo validation of the bold mechanism: A review of signal changes in gradient echo functional MRI in the presence of flow

Abstract Brain functional magnetic resonance imaging (FMRI) is possible because of local changes in blood flow and oxygenation levels. Understanding the role of each mechanism is important for interpreting FMRI results as well as for the design of the experiment itself. In this review, we address the role of flow and blood oxygen level dependence (BOLD) and how they can be used in conjunction with each other to enhance the BOLD effect. We also discuss the role of intra/extravascular signal changes in the presence of a vessel for the imaging situation and show how the ratio of these two contributions is likely to change as the blood volume fraction changes. Using the BOLD model itself, along with 3‐D phase imaging, we show that blood oxygenation level in veins in vivo is Y = 0.544 ± 0.029 as measured in 14 vessels in five subjects. Finally, we comment on the use of phase images themselves as a means to discriminate tissues with different levels of blood such as gray matter, white matter, and cerebrospinal fluid.