Precision Pictures

Magnetic resonance imaging (MRI) has helped innumerable patients afflicted by everything from cancer to stroke. And its movie-like cousin, functional MRI, has not only been useful for thousands of patients but has also dramatically improved our understanding of the brain. Its impact is suggested by the striking MIT discovery that when you look at virtually any type of place — a house, a lake, a mountain — the same tiny patch of your brain lights up. Or as MIT’s Alan Jasanoff puts it, “fMRI has a unique capability of imaging many types of brain functions, and doing so without the need for any invasive procedures.

In conventional fMRI, though, the information comes from changes in blood flow that only indirectly reflect what goes in the target organ. This gives the technology great power in imaging large sectors of the brain. But people like Jasanoff, the Norman C. Rasmussen Assistant Professor of Nuclear Engineering — using a computer analogy — in effect want to get down to the level of the individual transistors etched by the millions into computer chips.

“We’d like to get very precise information from MRI scans,” he notes, “including detailed information about neural circuits.”

It’s a tall order. The brain has roughly 100 billion of the computational cells known as neurons, each with hundreds or thousands of links to its fellow neurons — a degree of complexity that’s unmatched almost anywhere else in nature. (What does 100 billion mean? If each cell was activated in turn for a single second, and if each activation could somehow be tracked with an MRI scanner, it would take 3,000 years to cover the whole brain.)

Meeting the challenge, though, could yield large payoffs. In medicine alone, the technology could provide invaluable information on topics from planning precision brain surgery for a severely epileptic patient to exploring blindness linked to highly localized brain defects.

Jasanoff is developing tools called contrast agents to help sense neural activity at the level of individual cells.

To enter cells, these MRI-associated explorers have to be small — very small. Take the agent Jasanoff and his co-workers are developing to measure the in-cell build-up of calcium, long known as a sure indicator of an activated neuron. The imaging agent is some 50 nanometers across, or minuscule enough for well over a million copies to fit into a single cell.

But small alone isn’t enough. When calcium enters a cell, the contrast agent acts like a spy who’s ready to switch sides — “the calcium can trigger a molecular change in the makeup of the contrast agent,” says Jasanoff. That change, in turn, can make clusters of the agents within cells visible on an MRI scan, says the faculty member, who also holds an appointment in the brain and cognitive sciences department.

The possibilities, once Jasanoff and his co-workers perfect their methods, could include providing what amounts to a detailed map of exactly where and how, say, an external stimulus — a light flash, a spoken word — is registering in the brain. And it’s an approach applicable to other key brain chemicals besides calcium: one is dopamine, whose relative absence is the main culprit in Parkinson’s disease; another is acetylcholine, linked to Alzheimer’s.

Creating agents that can reliably lead you to such natural chemicals — and from there to a new understanding of how the brain works — is a grueling enterprise, not unlike the years-long obstacle course facing drug developers before they can even think about testing a new compound in patients. “There’s a really complex physics that goes into making these imaging systems work,” explains Jasanoff, “and things that can go wrong each step of the way.”

Despite the pitfalls, Jasanoff — the son of two Harvard professors, husband of a molecular biologist, and son-in-law of an MIT mathematician — says he loves the work. “It’s hard, it’s stressful, it’s intense,” he concedes, “but it’s also very intellectually challenging.”

by Richard Anthony « Previous | Next »

On Topic: faculty, health science+technology