September 28, 2000

UPTON, NY - The search for clues about multiple sclerosis (MS) -- a chronic, often disabling disease of the brain and spinal cord -- got a significant boost today when the National Multiple Sclerosis Society awarded a $613,687 grant to scientists at the U.S. Department of Energy's Brookhaven National Laboratory. The grant will support a three-year study using Brookhaven's powerful magnetic resonance imaging (MRI) scanner to look for early signs of disease.

"With Brookhaven's high-field magnetic scanner, we'll be able to detect quantitative changes in the brain at an earlier stage, and hope to learn more about the disease process," said William Rooney, the chemist leading the study. More than twice as powerful as a typical hospital scanner, the Brookhaven MRI machine will allow scientists to search for subtle changes in blood vessels that precede MS disease activity. Understanding these changes could lead to more effective diagnosis and treatment.

MS is characterized by scarlike lesions in the brain and spinal cord. It can lead to a range of symptoms from mild numbness to severe paralysis or loss of vision. Each year, approximately ten thousand new cases - about one an hour - are diagnosed.

Scientists believe that an early step in lesion formation is an influx of water into the brain via leaky cerebral blood vessels. When that happens, the body's immune cells attack the insulation surrounding nerve cells, leaving them less able to transmit electrical signals. The leaky blood vessels may reseal, but the multiple scars, for which the disease is named, remain.

"The question we want to ask," says Rooney, is: "Is there anything different about this tissue that we can detect before the lesion appears?"

The current study will make detailed measurements of water content across all areas of the brain in MS patients and control subjects. Earlier studies have shown increased water in the brains of MS patients as compared to normal controls, and in brain tissue that goes on to develop MS lesions as compared to brain tissue that doesn't.

"We'll be looking for the microvascular changes that may lead to this large and transient influx of water," Rooney says.

Study subjects will first be injected with a paramagnetic contrast agent that interacts with water in a way that makes the water more visible and quantifiable by the scanner. By taking multiple scans over a few hours, the scientists will follow how the contrast agent - and therefore also fluid - is transported out of the brain's blood vessels and into the brain tissue. (The agent washes out of the brain and body shortly after the examination.)

In normal subjects, the so-called blood-brain barrier lining the brain's blood vessels insures that the brain stays tightly sealed, to maintain stable volume and keep toxic substances out of this vital organ. But the scientists suspect that water and other substances move more easily across the blood-brain barrier in MS patients.

The scientists will re-examine the subjects each month to look for changes over time, and follow the development of MS lesions to see if they can be correlated with the brain's permeability to the contrast agent.

Are the patients with the leakiest blood vessels more likely to have more lesions? Is the blood-brain barrier leaky over the entire brain, or just in the regions where lesions form? Are people with "leaky" vessels more susceptible to the disease? These are just some of the questions Rooney hopes to answer.

Researchers may also use the technique to learn whether any of the drugs currently used to treat MS might reverse blood-vessel leakiness and possibly prevent the formation of lesions.

The study will be done in collaboration with Patricia Coyle, Medical Director of the MS Center at the State University of New York at Stony Brook. She will recruit approximately 25 patients with relapsing-remitting MS, the most common form of the disease, and 25 normal control subjects.

"Through this work, we will improve our understanding of the MS disease process," says Rooney, "and help determine the feasibility of extending these techniques to the study of other disease states, such as Alzheimer's, brain tumors, and even human immunodeficiency virus [HIV]."

The U.S. Department of Energy's Brookhaven National Laboratory creates and operates major facilities available to university, industrial and government personnel for basic and applied research in the physical, biomedical and environmental sciences and in selected energy technologies. The Laboratory is operated by Brookhaven Science Associates, a not-for-profit research management company, under contract with the U.S. Department of Energy.


Note to local editors: William Rooney lives in Miller Place, New York.

Above are contrast reagent distribution maps for control (top) and MS subjects (bottom). At the bottom of each image is the sagittal sinus - a large draining vein that has a very high contrast agent concentration. The greenish areas in the white matter of the MS subject's image are regions of increased contrast agent concentration - roughly about 50% higher than normal. BNL researchers hope to to determine if regions such as these are at increased risk for developing lesions compared to regions with normal contrast agent levels.