By Ryan Topfer
PhD Candidate at Polytechnique School of Montreal
“The popularity of magnetic resonance imaging (MRI) owes much to its flexibility. Sensitive to a host of different biophysical phenomena, parameters of the scan can be fine-tuned to highlight specific pathologies. One such mechanism for generating image contrast is magnetic susceptibility—the material property that defines how an object will distort an applied magnetic field such as that of the MR scanner. In functional MRI (fMRI) the unique magnetic signatures of oxygenated (diamagnetic) and deoxygenated (paramagnetic) blood are what permit the indirect measure of neuronal activity.” 
Over the last 30 years, fMRI evolved from its initial demonstration in rodents into a tool which has revolutionized the field of neuroscience. Though it is Seiji Ogawa who is credited with having discovered the blood oxygenation-level dependent (BOLD) effect on which fMRI is based, the scientific discoveries necessary for this insight went back over a hundred years and involved thousands of people.
In the mid 19th century, a debate was underway among scientists regarding the localization of brain function. It was Paris physician Paul Broca around 1861 who first evinced the material basis for this localization: Through autopsy, Broca examined the brains of patients with a history of language impairment and consistently found lesions (abnormalities) in a specific region of the brain’s frontal cortex (an area that now bears his name).
Some thirty years later, the English physiologists Charles Roy and Nobel prize winner Charles Sherrington discovered a relationship between blood supply (flow) and cellular activity. Now in the 20th century, another Nobel prize winner, Linus Pauling, discovered that the magnetic properties of hemoglobin (the protein in blood responsible for delivering oxygen to tissue) changed when it gave up its oxygen (thereby exposing the protein’s iron). Around the same time, in the 1930s local neurosurgeon Wilder Penfield discovered that the oxygenated hemoglobin in the brain actually increased when the brain was stimulated.
The phenomenon of nuclear magnetic resonance and its evolution into an imaging technique over the following several decades involved the efforts of scores of scientists and resulted in a number of Nobel prizes. It wasn’t until the late 1980s that Seiji Ogawa, informed by previous test tube studies, was able to demonstrate changes in the MRI signal in animals based on neural activity. He relates the essential experiment as follows :
Images “of the rodent brain showed many dark lines which had not been discussed by anyone previously… These lines were strongest in the dead brain. During an MRI experiment with an anesthetized mouse, I saw most of the dark lines disappear when the breathing air was switched to pure O2 in order to rescue the mouse as it appeared to start choking. This observation rang a bell. I did another experiment in which a mouse was [euthanized] with CO in order to leave CO hemoglobin (diamagnetic) in the blood when the mouse died. As expected, there were no dark lines in [the] images of the dead brain. The cause of the dark lines was identified as the… red cells containing paramagnetic deoxyhemoglobin.”
It was thus understood that neural activity could be observed indirectly with MRI as the response of the vascular system to such O2-demanding activity would be to overcompensate, pumping in more diamagnetic O2-rich blood. Hence, the localization of brain activity for a given task can now be examined in real-time without the mess of physically cracking open the cranium, something which Paul Broca would surely have appreciated.
 Topfer, R. Harmonic Phase Processing in Magnetic Resonance Susceptibility Imaging, MSc Thesis, 2014. University of Alberta.
 Ogawa, S. Finding the BOLD effect in brain images, 2012. NeuroImage.
 Estep, J. Semblance of fact, 2013. Triple Canopy.