Bright spots & black holes: what doctors are learning from advanced MRI.

What doctors are learning is not comfortable news. We present the technical details for those of you who want to know how these techniques apply to understanding MS.

The bottom line is brief: uncontrolled MS damages the central nervous system--the brain and spinal cord--and for many people the damage will, in time, be permanent. The fatty material that protects nerve fibers (myelin)is destroyed and replaced by scarring; and so, it turns out, is some gray matter (nerve cells as well as the nerve-cell fibers, or axons). Black holes and overall shrinkage of the brain, called atrophy, may occur. The sooner disease-modifying therapy is begun, the more effectively this damage can be delayed or prevented.

In other words, new findings confirm the wisdom of the National MS Society Consensus on Disease Management, issued in 1998. We urge you to discuss this with your persona physician and to reach out for counseling and support by contacting your Society chapter.

Fifty years ago, MRI was called NMR. The letters stood for "nuclear magnetic resonance" and it was used in laboratory research. Then, late in the 1970s, as computer technology improved, NMR was enlarged, modified--and renamed. The developers were skittish about trying to persuade people to use a medical imaging device with the word "nuclear" in it. The name "magnetic resonance imaging" was adopted.

The basic technology didn't change. Then and now, there is no radiation or nuclear energy involved in MRI. It uses radio waves and magnetism.

A strong magnetic field makes the hydrogen protons in water molecules line up; then radio waves knock the protons out of line. When the radio waves are stopped, the protons relax back into line, releasing "resonance" signals, which are transmitted to a computer. Fancy computer programs convert these data into a picture--of water. The water in living human tissues.

Where fat isn't, water is

Because the myelin layer that protects nerve-cell fibers is fatty, it repels water. Thus, MS damage reveals itself on MRI because areas that are stripped of fatty myelin hold more water. MS lesions, or damaged areas, show up as bright spots.

Early in the 1980s, the first serial MRI scans of people with MS changed physicians' fundamental understanding of this disease forever. Those pioneering MRI studies revealed that MS is a constantly active on-going disease from the very beginning.

Even when a person with MS is in remission and feels well, events are taking place in the brain or spinal cord. Some MS doctors call these events "explosions in the brain." MRI studies demonstrate that they happen five to ten times more frequently than visible MS relapses or attacks.

A reliable measurement

Today, MRI is an essential measure of MS activity. Researchers can count the number and measure the size of lesions, and that gives them an objective measure of multiple sclerosis activity. In a slow-moving, notoriously variable illness like MS, researchers had been hard-pressed to find a benchmark for evaluating the effect of treatments. MRI data are simple: smaller and fewer lesions = good; more and larger lesions = bad.

The big glitch is the lack of clear correlation between the MRI picture of MS and the clinical picture of MS--which is how a person feels or acts in daily life. But as MRI technology has marched forward, it has become more and more clear why fewer and smaller lesions = good. Over a longer term, the total extent of damage seen on MRI is definitely related to a person's disability. Indeed, some of the cognitive problems people have--with memory, word-finding, or problem-solving--have now been linked to the location of lesions as well as to their number and size.

"Gadolinium enhancement" sees active inflammation

Gadolinium is a contrast agent. Infused into the bloodstream a few minutes before an MRI, it lights up areas where immune-system cells are leaking out of tiny blood vessels and into the central nervous system. This is a hallmark of active inflammation, a key event in the MS attack on myelin. (Normally, immune cells are kept away from brain tissues by the blood-brain barrier, a layer of specialized cells inside capillary walls.)

Studies show that a gadolinium-enhancing lesion lights up for three to six weeks and then fades. Thus these scans are indicators of active disease during the preceding 45 days or so.

Unfortunately, fading doesn't always mean a lesion has fixed itself and disappeared. It may remain on a "T2 weighted" MRI scan.

T2 weighted scans give a good one-year look back

The MRI computer program can produce pictures based on two different proton relaxation times, called T1 and T2 weighted scans. The T2 scans reflect the level of disease activity in the preceding year. The lesions these scans reveal continue to show up as high-water bright spots after the gadolinium enhancements have gone away. They are referred to as plaques. Occasionally lesions repair themselves and disappear forever. Others reinflame later on, sometimes again and again. Over time, scientists have learned, repeated inflammation changes their nature altogether.

T1 weighted scans reveal tissue loss

Dark areas on the T1 weighted scans point to loss of myelin and loss of the nerve fibers, or axons. These areas are named for what they look like: "black holes". The darker the spot, the more extensive the tissue loss. They develop where a lesion has been re-inflamed time and again.

As one clinician put it, "Black holes are where a plaque used to be. The area is now totally inactive."

Black holes do correlate with the clinical picture. Individuals with black holes have permanent disabilities.

"MTR" MRI zeroes in on tissue loss

MTR, or magnetization transfer ratio, delivers an extra pulse of energy to the protons that are bound to myelin and then measures how much of that energy is transferred to the free water nearby. These calculations allow researchers to estimate more precisely how much tissue damage has occurred in specific lesions.

"MRS" MRI sees more than water

Magnetic resonance spectroscopy, or MRS, brings MRI full circle because the technology was originally developed not to make images of human beings but to scan laboratory samples for the presence of specific chemicals. MRS can measure the amount of important marker chemicals in nerve cells and axons, including, for example, a key byproduct of nerve-cell breakdown, providing yet another way to calculate how much permanent damage has occurred.

Coming soon ...

The potential of MRI for revealing bodily processes in action within a living human being has not peaked. Among the newer techniques is one called "tractography", or "diffusion weighted imaging" and "diffusion tensor imaging". Focusing on white matter (the myelin-dense areas of the brain), this technology can outline the individual fiber tracts of nerve cells.

MRI machines with much bigger magnets are also being developed. The garden-variety MRI device has a 1.5 Tesla magnet, roughly as powerful as the magnets used in junkyards to pick up automobiles. An experimental 8 Tesla magnet at the University of Ohio has produced extraordinarily detailed images--and is so powerful it unhooked the bra of a visitor standing at a respectful distance outside. MRI will continue to provide scientists with insights on MS.

Back to the day-to-day: How often should I have an MRI?

Most of the MRI applications described here are for research studies only. They are done to answer questions about MS, not to guide the care and treatment of an individual. Frequent, or "serial", MRIs produce useful research information only if head position, scan power, and other factors are replicated exactly.

We took the everyday question to two members of our editorial board--Patricia Kennedy, RN, CNP, at Colorado's Rocky Mountain MS Center, and Loren Rolak, MD, at Marshfield Clinic in Wisconsin.

"I'd advise patients to ask for an MRI every two years," Kennedy said. "An MRI helps clarify those hidden exacerbations. We can see if a disease-modifying therapy is doing its job. And for those who are not on therapy, we can track changes, which may help persuade the person to opt for therapy after all. Here at Rocky Mountain we feel MRI is an established part of the clinical picture."

But Rolak feels MRI offers him little help on how to treat most of his patients once they have been diagnosed. "The data on adjusting treatment based on MRI changes alone just aren't conclusive yet," he said. "I change medications in response to side effects or other clinical factors."

In short, like so much else in MS, the answer varies from person to person and from circumstance to circumstance.