Beyond blood: next-generation MRI scans offer a sharper picture of the brain's inner workings

Science News,  March 15, 2008  by Ewen Callaway

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The test subject lies on his back, legs stretching from the tunnel-shaped brain scanner. Flat-screen computer monitors fill the cramped control room for the MRI machine. The subject watches one screen, where phrases flash, such as "Jesus is the son of God," "God puts good and evil everywhere," and so on.

"We're doing a study on religion in the brain," says the technician at the National Institutes of Health (NIH) in Bethesda, Md.

Another monitor reveals a black-and-white cross section of the subject's brain. The picture refreshes every few seconds. The image is mostly a blur, but some smears appear brighter, others darker. It's the brain on religion.

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The scanner isn't taking photos of brain cells contemplating the afterlife. Instead, the snapshots capture blood flowing to the cells. Scientists call this measurement BOLD--short for blood-oxygen level-dependent. More blood equals more thought, the theory goes. Combined with traditional MRI (magnetic resonance imaging), the technique has revolutionized neuroscienee, providing tantalizing glimpses into the biology of cognition.

Scientists call this method of scanning a brain at work functional MRI, or fMRI. Today, nearly every fMRI study relies on blood flow.

However, many scientists say that, while useful, blood flow is an indirect gauge of brain activity at best, and misleading at worst. More precise measures of the mind will offer clearer and more complete pictures of human and animal brains at work.

"Using BOLD to study how the brain works is a little bit like feeling different parts of a computer--feeling how hot they are--and trying to understand how it works based on that," says Alan Jasanoff, a neuroscientist at the Massachusetts Institute of Technology and a leading proponent of the budding field of bloodless MRI. He studies chemicals that brighten the magnetic signal revealed by an MRI scanner. Other researchers hope to tap the minuscule electric currents that flow through neurons, while still others hunt for subtler physiologic changes.

Although still in its infancy--and flush with ideas but short on results--bloodless MRI will someday usher in a sea change in our understanding of the brain, its proponents say. The new techniques could provide more detailed maps of brains, illuminate the connections between distant regions of the brain, and diagnose diseases like Alzheimer's.

LEAKY PIPES Early efforts to map the human brain were as invasive as they were primitive. In the 19th century, scientists linked form to function by dissecting the brains of deceased patients. Surgery offered another window into the mind, as physicians prodded brains. Gentler techniques, such as electroencephalography (EEG) and positron emission tomography (PET) emerged, but suffer other shortcomings. PET releases radiation that is potentially dangerous, and EEG only picks up superficial waves.

Functional MRI seemed like the perfect solution. It is noninvasive and measures brain activity via blood flow with the same machine that diagnoses a badly sprained ankle. The scanner generates an enormous magnetic field tuned to physiologic signals--the hemoglobin in blood, for instance. Then, while a test subject performs a task, such as viewing pictures, the MRI scanner records brain activity. Computers translate the whole affair into a 3-D map, indicating which areas lit up during the task and which dimmed.

Invented in the early 1990s, fMRI was slow to catch on. But the technique eventually became a blockbuster among neuroscientists, says the NIH's Peter Bandettini, an early pioneer who has undergone thousands of scans himself.

In an early experiment, Bandettini alternately tapped his left and right fingers while lying in the scanner. A movie captured the effect: A white smudge, where blood flow increases, jumps between the right and left sides of his motor cortex, a brain region responsible for movement.

For all its usefulness, fMRI measures blood flow, not electricity, the lingua franca of neurons. "The first time I went to an MRI meeting I felt like an electrician in a plumbers' convention," says Nikos Logothetis of the Max Planck Institute for Biological Cybernetics in Tubingen, Germany.

Another common gripe against BOLD is the lag between electrical brain activity and blood flow, Jasanoff says. Tap a finger, and : neurons in the motor cortex pulse. Blood soon flows through capillaries to the cells in the motor cortex, but the BOLD signal peaks when blood courses through bigger vessels and subsides several seconds after the initial finger tap. This delay means that when several regions of the brain light up in succession, the BOLD signal might mask the order of activation.

"If you think about what you do with your brain, you would agree that 5 seconds is actually an infinity," Jasanoff says. Imagine driving a ear with a 5-second lag between seeing a curve and turning the steering wheel.