Is there a path beyond BOLD? Molecular imaging of brain function

The dependence of BOLD on neuro-vascular coupling leaves it many biological steps removed from direct monitoring of neural function. MRI based approaches have been developed aimed at reporting more directly on brain function. These include: manganese enhanced MRI as a surrogate for calcium ion influx; agents responsive to calcium concentrations; approaches to measure membrane potential; agents to measure neurotransmitters; and strategies to measure gene expression. This work has led to clever design of molecular imaging tools and many contributions to studies of brain function in animal models. However, a robust approach that has potential to get MRI closer to neurons in the human brain has not yet emerged.