Seen at Last: The Brain at Work

Canadian Reader’s Digest, January 1984
Feature, 2100 words

On March 5, 1979, a Medical Center technician at the University of California at Los Angeles (UCLA) injected a sugarlike, radioactive liquid into an intravenous line in the arm of Charles Blackburn (not his real name), a healthy, 24-year-old computer programmer. Blackburn was a volunteer in an extraordinary experiment. For the next two hours, a fabulous new machine called a positron emission tomography (PET) scanner would take a picture of what was going on inside his brain.

Blackburn lay on a stainless-steel table with his head in the scanner. It looked like an enormous metal box—more akin to a clothes dryer than a marvel that can actually see a human brain function. Blackburn was not worried about the radioactive sugar traveling to his brain, where detectors in PET's camera could "see" it and report its location to a computer. After all, he reminded himself, the radiation he would receive would be minimal.

His ears plugged to keep him from being distracted, Blackburn concentrated on a plain white light displayed on the wall. Soon 12 cross-section "slices" of his brain appeared, one after the other, on the computer's video screen, like slices of a loaf of bread. They showed, amazingly, that when he looked at the light, the primary visual cortex at the back of the brain shone like a bulb on a Christmas tree.

When Blackburn's portraits were finished, the PET scans appeared in glorious color. And biochemist Michael Phelps and neurologist John Mazziotta, who designed the experiment, thanked him for his part in a trail-blazing event.

The PET scanner fulfills a fantasy that neuroscientists have had for years: seeing the brain at work, in three dimensions, with minimal risk to the subject. Despite the astronomical cost of the equipment—over $2 million for installation of a PET machine and the cyclotron to make the radioactive chemicals it requires—and of assembling an expert team of scientists and physicians to run it, there now are 22 of these brain scanners in the world. Four Canadian institutions have them: the Montreal Neurological Institute (MNI); McMaster University Health Centre, in Hamilton; Queen's University Faculty of Medicine, in Kingston; and the University of British Columbia's Imaging Research Centre, in Vancouver.

And PET is well worth the expense. "It's one of the most important developments ever to happen in brain sciences," says Dr. Herbert Pardes, director of the U.S. National Institute of Mental Health in Rockville, Md. Dr. William Feindel, director of the MNI, calls PET "an enormous window into the chemistry of the living brain."

The brain is really the last great medical frontier. Our information about this extraordinarily complex organ is incomplete because so much of what we want to know can be seen only in living people, and our ways of exploring that terrain have been limited.

Until recently, technology has allowed scientists to see only the brain's structure. Now, PET shows activities that take place within the structure, like seeing and hearing, thinking and feeling, moving and remembering. Think of the brain as a car engine, suggests Dr. Antoine Hakim of the MNI. By looking at it, "we can open the hood of the car and see belts and valves and other machinery. But that doesn't give us any idea of what the engine does or how. PET scanning allows us to put a tracer on the gasoline and air and see where this mixture goes—how it creates motion."

The brain's primary fuel is sugar or glucose, and in the late 1970s neurochemists found a substance that mimics sugar, tagged it with a radioactive isotope and devised a way of using it to measure the rate of utilization of glucose by the brain. As the radioactive sugar travels around in the bloodstream with the ordinary sugar, leaving a trail of its whereabouts like the crumbs of Hansel and Gretel, it fools the brain into metabolizing it just as if it were the real thing.

Because it isn't ordinary glucose, but rather its radioactive cousin, FDG, it gets stuck. Its positron-emitting radiation, meeting the normal inhabitants of living cells, electrons, sets off a bizarre event: Positrons and electrons annihilate one another, creating gamma rays. The PET scanner locates the gamma rays and sends this information to the PET computer, which turns it into pictures. They show which parts of the brain are working the hardest—those consuming the most glucose—and which are idle—those using the least glucose. The computer, programmed to indicate just how intense the activity is, can provide pictures in different shades of gray, or in colors ranging from white and red, which typically represent lots of activity, to violet and blue, which represent little activity.

A musical mystery. On May 9, 1979, Sam Cohen (not his real name), a 21-year-old student, reported to the UCLA Medical Center to take part in a more complex PET experiment devised by Phelps and Mazziotta. The research team had Cohen sit in a wheelchair. Immobilized, his cars plugged to minimize input to other parts of his brain, he was wheeled out to busy Westwood Boulevard. The researchers wanted to see how his brain looked while he was watching a complex street-scene. Would it look any different from a brain watching plain white light?

A technician injected radioactive sugar into an intravenous line in Cohen's right arm. For the next 40 minutes, Cohen gazed at the scenery while the radioactive sugar wended its way to his brain. Then his eyes were patched to preserve the image now in his brain and he was rushed back to the medical center. The team took pictures before the radioactivity in the sugar dissipated.

When they analyzed them, the researchers were delighted to see in the back of the brain, the part that deals with vision, a red area larger and more brilliant than the area they'd seen lighted up in the brain watching white light. The more intense red corresponded to the part of the brain thought to make complex visual interpretations. PET had confirmed an accepted "fact": This part of the brain works harder when it looks at more complicated scenes.  

After the vision experiments, UCLA researchers entered less charted territory. Conventional wisdom has it that right-handed people use the left side of the brain for language, and the right for artistic and emotional matters. But in May 1980, when Christopher Englander (not his real name), a right-handed, 24-year-old student, listened to sequences of notes and tried to figure out whether or not they were alike, PET revealed another of the brain's mysteries. Unlike other volunteers who heard these same notes, Englander's brain turned brilliant red on the left, or language, side, not on the right "artistic" side. Had he listened differently, asked the puzzled scientists? Yes, explained Englander, he had visualized the scale and put the notes on it in his mind.

Next, the researchers tested a professional musician. The left side of his brain, too, lit up like a neon sign. The conclusion? Those who approach the problem analytically use the left side of their brains, while those who sing the notes and try to solve the problem intuitively use the right. The significance? Says Mazziotta, "This demonstrates that two different brains can address the same problem in a different way."

As chemists develop tags for other substances in the body, PET will reveal more of the brain's wonders; and because it shows disturbances as well as normal activity, PET is already being used to investigate neurological diseases that still evade medicine's grasp:

• Brain tumors can be treated with chemotherapy, but until now no one has known whether the drugs were reaching their target or how effective they were. In Montreal, Drs. William Feindel, Lucas Yamamoto and Mirko Diksic have developed a method of radioactively labeling BCNU, an anticancer drug that shrinks brain tumors. The PET scanner shows that the drug gets into some tumors—primarily those that are growing rapidly—and not others, telling doctors which patients are likely to respond to chemotherapy. By revealing the concentration of BCNU in the tumor, PET also allows doctors to treat patients with the optimal dose, rather than just bombarding them with the largest their bodies can tolerate.
  
  
• Epilepsy doesn't always respond to medication, and for perhaps 30 to 50 percent of epileptics like Adell Forbush, a pretty red-haired teenager in Brea, Calif., PET brings new hope. When 17 pills a day could no longer control her seizures, Adell and her family despaired. Surgery seemed a promising solution, but conventional diagnostic techniques failed to show which part of her brain was damaged. Then, during two weeks of extensive tests in Dr. Jerome Engel Jr.'s epilepsy unit at UCLA Medical Center, PET pinpointed the area of Adell's brain that was not working properly. Because it used very little sugar, it was blue in the PET pictures. With this evidence, surgeons operated. Now 21 and seizure-free for four years, Adell Forbush is working in a bank.
  
  
• Parkinson's disease, which causes rigidity and tremor in many elderly persons, is associated with a deficiency of dopamine, a chemical that allows brain cells to communicate with one another. At McMaster, Dr. Stephen Garnett, chemist Gunter Fimau and physicist Claude Nahmias have used the PET scanner to "snap" dopamine in action in a living person for the first time. Its natural pathways in normal brains—red and pink on the scan—can be seen clearly when its radioactively labeled chemical cousin, fluorodopa, enters the brain and turns into dopamine. Doctors prescribe L-dopa to replace the dopamine lacking in victims of Parkinson's, but its effects are unpredictable. The McMaster team hopes its PET scans will show how the use of drugs can be improved.
  
  
• Stroke, which kills brain tissue by depriving it of blood and oxygen, is hard to treat effectively. But PET brings a new approach for the 550,000 North Americans felled by strokes each year. Using radioactive oxygen, radioactive carbon dioxide and FDG, the PET scans can distinguish between injured and dead tissue immediately after a stroke. Says Hakim, "With PET we can see which part of the brain has died, and which part is getting just enough blood to stay alive but not enough to work effectively." Hakim and his colleagues are also using PET to evaluate various medical and surgical therapies to see which ones restore function to injured tissue. In St. Louis, investigators are using PET to identify stroke patients who would benefit from surgery to bypass a blocked brain artery. In 1981 Edward Criger, 70, of Bonnots Mill, Mo., suffered attacks. "My whole body would go weak," says Criger. "I'd fall over if I didn't have a chair handy." Tests at Washington University Medical School showed a blocked artery in Criger's brain, but a PET scan revealed something even more frightening: a deep blue area just above the blockage where his brain was being starved of life-sustaining blood and oxygen. Doctors did bypass surgery to give his brain a new blood supply. Now his attacks have virtually ceased.
  
  
• Mental illness is the most difficult of all brain diseases to study because of the elusiveness of its physical base. But the PET scanner provides a handle on the neurochemical basis of behavior for the first time, raising hopes that such complex disorders as schizophrenia will finally be understood and therefore more easily treated.

By making earlier diagnosis possible through its ability to show changes in the functions of organs, PET is creating a new era in medicine. "If we can detect the first disorders before there are structural changes," says Dr. David E. Kuhl of UCLA, "we may be able to do something about it, rather than depending on diagnostic methods that show only the graveyard of the organ after the damage has been done. This is frontier research where we have learned a lot in a relatively short time." Adds Phelps: "It's an era in which we'll be able to enter the human body safely, wander around with our little chemistry kit, and measure what's going on."

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