The connection between Linus Pauling and fMRI

When I think of Linus Pauling, two things come to mind: his work on  the nature of the chemical bond (for which he was awarded the 1954 Nobel Prize in Chemistry) and, in his later years, his advocacy of Vitamin C. But Pauling is one of the great names of  20th century science. He contributed to a variety or domains and other connections can be made. His campaigning for a nuclear test ban won him a Nobel Peace prize. And his description of the molecular structure of blood -- of sickle cell anemia in particular -- is highly regarded.

 Pauling, in fact, had had a long interest in the properties of blood. In 1936 he published an important paper on the magnetic properties of hemoglobin [1]. Hemoglobin, which is a major component of blood, can be oxygenated or deoxygenated and it is due to this easy coupling and decoupling that it plays its key role as a carrier of oxygen. Pauling's experiments had shown that deoxyhemoglobin is paramagnetic (i.e.,  in layman's terms, has magnetic properties) and oxyhemoglobin is diamagnetic. The original paper is worth reading; I was struck by the clear, concise and objective manner in which these results are  presented.

Pauling did not envision an application at the time but from the mid-1960s on much work was done on engineering MR field gradients and studying the contrast they provided for different kinds of tissues. In 1990, Seiji Ogawa published a set of papers [2] showing that local inhomogeneities in the magnetic field were formed in response to  changing levels of deoxygenated blood and could be measured. This property became the basis of BOLD or blood oxygenation level dependent fMRI.

The connection  between neural activity and the MR signal  is roughly as follows: 

        increased local brain activity
               → increased blood flow 
                   → change (dilation) in size of blood vessel
                          → change (increase) in the deoxyhemoglobin concentration
                                → changes in the local magnetic field as measured by the MRI (T2*) signal. 

There is an excellent lecture on YouTube where Geoffrey Aguirre explains this. Another talk, this time by Christof Koch, also briefly mentions Pauling's paper.


References  
(1) The Magnetic Properties and Structure of Hemoglobin, Oxyhemoglobin and Carbonmonoxyhemoglobin.
Linus Pauling, Charles D. Coryell. Proc Natl Academy of Sciences. 1936 April; 22(4): 210–216.

(2) Brain magnetic resonance imaging with contrast dependent on blood oxygenation.
Seiji Ogawa et al.  Proceedings of the National Academy of Sciences. 1990; 87(24): 9868-9872.