Friday, January 22, 2016

A Brief History of Human Functional Brain Mapping

In Chapter 18 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I describe functional magnetic resonance imaging.
“The term functional magnetic resonance imaging (fMRI) usually refers to a technique developed in the 1990s that allows one to study structure and function simultaneously. The basis for fMRI is inhomogeneities in the magnetic field caused by the differences in the magnetic properties of oxygenated and deoxygenated hemoglobin. No external contrast agent is required. Oxygenated hemoglobin is less paramagnetic than deoxyhemoglobin. If we make images before and after a change in the blood flow to a small region of tissue (perhaps caused by a change in its metabolic activity), the difference between the two images is due mainly to changes in the blood oxygenation. One usually sees an increase in blood flow to a region of the brain when that region is active. This BOLD contrast in the two images provides information about the metabolic state of the tissue, and therefore about the tissue function.”
The amazing story of how, 25 years ago, two competing teams developed fMRI simultaneously is told by Marcus Raichle in his chapter A Brief History of Human Functional Brain Mapping, published in the book Brain Mapping: The Systems. Below I provide excerpts.
“A race was on to produce the first human functional images with MRI even though the participants were unaware of the activities of each other! Who were the participants? [Seiji] Ogawa and his colleagues working with Kamil Ugurbil and friends at the University of Minnesota and a group at the Massachusetts General Hospital led by Ken Kwong...

Ugurbil turned to a new postdoctoral fellow in the laboratory, Ravi Menon, to help in the effort to obtain the first functional MRI BOLD images in humans...He was joined by Ogawa and [David] Tank from Bell Labs along with members of the Ugurbil lab and a pair of Grass Goggles for visual stimulation!….It was early summer of 1991 that believable results were finally obtained. This was obviously too late to submit an abstract to the upcoming Society of Magnetic Resonance Conference to be held in San Francisco in August. Members of the laboratory, nevertheless, left for the meeting with slides in their pockets hopeful that they would have a chance to show some of their new results.

Meanwhile, a very parallel but completely independent set of events was unfolding in Boston. Ken Kwong, a member of the group at the Massachusetts General Hospital, was anxious to develop a method for measuring blood flow with MRI….Kwong saw a poster by Bob Turner, another MR physicist working at the NIH, which was of related interest. Turner had been studying hypoxia/ischemia in cats produced by brief periods of ventilatory arrest….They choose a visual activation paradigm. A pair of well-known Grass Goggles resided in the lab to support the function activation work using contrast agents….

Buoyed by the results obtained with the goggles and BOLD imaging, the MGH group rushed to submit a “Works in Progress” abstract to the Society of Magnetic Resonance Conference… Much to the MGH group’s dismay and to this day unexplained, this particular abstract failed to reach those putting the program together….Recognizing by this time the significance of their results, they persuaded Tom Brady to include their results in his plenary lecture. The group from Minneapolis had no such opportunity! Not only did the scientific world get its first glimpse of fMRI, but the two groups working on the concept also realized for the first time who the competition was!

By the early fall of 1991 both the Minneapolis and the Boston groups had publishable results. With great anticipation, papers were submitted to Nature (Minneapolis) and Science (Boston) and summarily rejected. The basic judgment of both journals was that they contained nothing new! It is fitting that the work of the two groups appeared together in the Proceedings of the National Academy of Science (Kwong et al., 1992; Ogawa et al., 1992). A new and very important chapter on functional brain imaging had begun.”
Functional MRI has since been used for many studies of how the brain works. I consider it one of the best examples of physics applied to medicine in the last 25 years. Raichle not only tells the story of fMRI's development well (but perhaps with too many exclamation points for my taste), but also reviews the long history of mapping brain function, dating back into the 19th century. The chapter is well worth a read. Enjoy!

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