The Foundations of Functional MRI

When the Martinos Center moved in to Building 149 in the Charlestown Navy Yard, it had a single MRI scanner for human studies: a recently purchased 1.5T system made by GE, which, as a company, was rapidly establishing a foothold in the MRI sphere. (The Center’s first FDA-approved clinical system, acquired in 1984, was made by Technicare, a company owned by Johnson & Johnson. When GE bought Technicare a couple of years later, “we kind of switched our corporate allegiance,” Center director Bruce Rosen says.)

Though the Center had only the one system at the time, Radiology chief James Thrall pushed for construction of three scanner bays in the Navy Yard, believing the group would soon outgrow a single bay there. While this would require a significant investment, Thrall argued that the facility would ultimately recover the funds by creating a self-liquidating cost center, in which time spent on the scanner would be charged to research grants held by Center investigators and other, outside users—a model still in use today.

The bet would soon pay off. Not long after the move, the Center acquired an MRI scanner with “echoplanar imaging” capabilities made by Advanced NMR Systems—the company started by Ian Pykett, Rosen’s former thesis advisor, after he left Mass General. The scanner installed in the Center was the first-ever clinical system with such capabilities. Echoplanar imaging offered greatly reduced acquisition times with MRI, on the order of milliseconds, and thus enabled a host of new applications with the modality.

Not least: Rosen and the Center’s Jack Belliveau used it to characterize a phenomenon that Rosen and his postdoctoral fellow Arno Villringer had both observed with MRI after injection of a contrast agent: a rapid initial

drop in the signal measured followed by a slow return to baseline. This work led to the development of the imaging technique now known as dynamic susceptibility contrast MRI, which enables measurement of blood flow and other, related parameters.

Thus they set in motion the series of events leading to the introduction of functional MRI. First, Belliveau, a Harvard graduate student working in the Center, demonstrated a practical application of the new technique in the diagnosis of stroke. Belliveau was also intrigued by the possibility of using the technique to measure changes in local blood flow following neural activation. In 1991, he and colleagues published in the journal Science the first magnetic resonance images of brain activity related to visual processing, launching a new era in functional brain imaging.

Because it involved injection of a contrast agent, the technique described by Belliveau was limited to only a couple of scans at a time. In 1992, less than six months after publication of the Science paper, Kenneth Kwong, a postdoctoral fellow in the Center, described a means of achieving intrinsic contrast—that is, contrast based on innate biological processes—thus addressing the most significant remaining challenge with functional MRI and opening the door to the many thousands of studies reported in the nearly three decades since.

The following is the story of these two studies and the brilliant if occasionally eccentric Martinos researchers who made the studies happen.