Getting the Word Out

After completing his experiments with functional imaging with endogenous contrast, Ken Kwong submitted an abstract describing the “work in progress” movies of brain activation to the 10th annual meeting of the Society for Magnetic Resonance in Medicine (SMRM), to be held in San Francisco in August 1991. But the abstract was lost in the mail, leaving the announcement of the discovery of fMRI to a mention in a paper presentation session by Bernice Hoppel and the brief video in the plenary lecture by Thomas Brady. Even this brief glimpse of the results made an impact, though. “It was certainly not Hollywood quality,” Bruce Rosen wrote of the video in the 2012 Neuroimage paper [1], “but many people in the audience appreciated its potential immediately; and for some, it changed the course of their careers.”

Rejection letter from Nature, dated 5 December 1991

Among them, perhaps: Peter Bandettini, then a graduate student at the Medical College of Wisconsin. Bandettini recalls seeing a “jaw-dropping movie” at the meeting and then returning home and initiating similar experiments using Kwong’s method to measure changes in brain activity [2]. These experiments would prove very important – to him and to the community at large. Kwong and colleagues wrote a “broad and comprehensive” paper reporting the fMRI phenomenon and, in October, submitted it to the journal Nature. But the paper was rejected, in part because one of the reviewers seemed to have missed the significance of the findings: that is, dynamic mapping of the brain using only endogenous contrast. (“If the point of this paper is that MRI can be used to map the brain, this point has been made in the Science paper [by Belliveau et al.],” the reviewer wrote. “If the point of this paper is that MRI can shed new light on the regulation of cerebral hemodynamics and metabolism by neural activity, I am not yet convinced.”) Undeterred, Kwong and colleagues expanded the scope and depth of the paper and submitted it to the Proceedings of the National Academy of Sciences (PNAS) in 1992. This paper – “Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation” – was accepted and published in June [3]. Two other important papers appeared at about the same time. In “Time course EPI of human brain function during task activation,” published in the journal Magnetic Resonance in Medicine earlier in June [4], Peter Bandettini reported changes in MR signal during a finger tapping exercise – noting that he had decided to perform the experiments after hearing Thomas Brady’s talk at the SMRM meeting. A third paper, “Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging” by Ogawa and colleagues, appeared in July in PNAS [5]. With these experiments, Kwong and the others demonstrated that imaging of cerebral activation using endogenous contrast was possible. They showed that they could observe changes in the brain following sensory stimulation without having to use external contrast agents. It remained now to explore the potential of the technique, to find out what could be learned in applying it. As it turned out, a number of investigators were eager to do just this.

Ken Kwong and John Baker prepare a volunteer for a "fast MRI" (top). Brain images from such an imaging study (bottom). Both are from an article in the October 1992 issue of MGH News.

REFERENCES 1. Rosen, B. R. and R. L. Savoy (2012). "fMRI at 20: has it changed the world?" Neuroimage 62(2): 1316-1324. 2. Bandettini, P. A. (2012). "Twenty years of functional MRI: the science and the stories." Neuroimage 62(2): 575-588. 3. Kwong, K. K., J. W. Belliveau, D. A. Chesler, I. E. Goldberg, R. M. Weisskoff, B. P. Poncelet, D. N. Kennedy, B. E. Hoppel, M. S. Cohen, R. Turner and et al. (1992). "Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation." Proc Natl Acad Sci U S A 89(12): 5675-5679. 4. Bandettini, P. A., E. C. Wong, R. S. Hinks, R. S. Tikofsky and J. S. Hyde (1992). "Time course EPI of human brain function during task activation." Magn Reson Med 25(2): 390-397. 5. Ogawa, S., D. W. Tank, R. Menon, J. M. Ellermann, S. G. Kim, H. Merkle and K. Ugurbil (1992). "Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging." Proc Natl Acad Sci U S A 89(13): 5951-5955.