Finding Bipolar Disorder with MRI

This article – a feature story in Technology Review’s December 2005/January 2006 print issue – has been divided into three parts for presentation online. This is part 1; part 2 will appear on Tuesday, January 24, and part 3 on Wednesday, January 25.

When Bradley Peterson, a psychiatrist and researcher at Columbia University, offered to scan my brain with a magnetic resonance imager the size of a small Airstream trailer, I immediately said yes. I spent 10 minutes filling out a page-long checklist (I lied on the question asking whether I was claustrophobic) and another few minutes emptying my pockets and getting rid of keys, wristwatch, and pen, which could become missiles inside the MRI’s potent magnetic field.

I lay down on a narrow pallet that slid into the machine like a drawer in a morgue. The machine groaned and clanged as it peered inside my skull, then fell silent. With a gentle whir, the pallet slid out, and I relaxed. In about the time it takes to burn a few CDs on my laptop, Peterson was leaning over a screen, showing me a detailed black-and-white image of my brain.

Brain scans like the one I had are now routine, used for everything from detecting signs of stroke to searching out suspected tumors. But researchers like Peterson are pushing MRI technology further than anyone once thought it could go. In the last decade or so, MRI has been retooled to reveal not only the anatomy of the brain but also the way the brain works.

While conventional MRI scans, like the one Peterson gave me, reveal physiological structures, a variation called functional MRI (fMRI) can now also image blood flow over time, allowing researchers to see which areas of the brain are active during certain tasks.

Indeed, fMRI studies over the last few years have provided researchers with startling images of the brain actually at work. A yet newer extension is MRI spectroscopy, another kind of functional imaging that monitors the activity of particular chemicals in the brain – providing different clues to brain function than fMRI does. And most recently, researchers have pioneered an MRI technique called diffusion tensor imaging (DTI) that produces 3-D images of the frail, spidery network of wires that connects one part of the brain to another.

MRI has become, says Robert Desimone, director of the McGovern Institute for Brain Research at MIT, “the most powerful tool for studying the human brain. I liken it to the invention of the telescope for astronomers.” Desimone notes that the arrival of the telescope did not immediately revolutionize the scientific understanding of the universe. That took time, as researchers learned how to use their new tool.

The same thing is happening with MRI, Desimone says. Researchers are just now beginning to realize the potential of these techniques, which were first widely used on humans about 15 years ago. “You’re seeing a lot of excitement in the field,” says Desimone.

Several technical advances have contributed to MRI’s improvement. Topping the list is the development of more-powerful MRI magnets, which enable more-detailed, higher-resolution scans. What megapixels are for a digital camera, teslas, a measure of magnetic-field strength, are for MRIs: the more you have, the better the quality of the image. The newest MRIs generate magnetic fields of about seven teslas, many thousands of times stronger than Earth’s magnetic field and at least twice as strong as those typically used in hospitals. (Some research centers, including the McGovern Institute, have 9.4-tesla MRI scanners for animal studies.)

Another key development is a succession of ever more complex methods of computer analysis. These allow researchers to extract more and better information from scanner data and have improved not just fMRI but also MRI spectroscopy and DTI.

The ultimate aim of brain imaging research is to help explain how the billions of neurons and connections in the brain give rise to thought. But researchers are also applying the new MRI techniques to a more practical, immediate goal: improving the diagnosis and treatment of mental illnesses and learning disorders. The hope is that MRI imaging will provide far more accurate diagnosis of psychiatric diseases whose symptoms can resemble each other, preventing years of suffering for patients put on the wrong medications.

As part of this effort, researchers are using MRI to investigate the causes not only of psychiatric ailments but of all kinds of brain abnormalities and learning disorders, including those often found in children born prematurely. And while attempts to use brain imaging to improve psychiatric health care have met with little success over the last decade, the new MRI technologies – in essence, far stronger telescopes on the mind – are providing fresh hope of finding better ways to intervene.

Bipolar Fingerprint

One of the leaders in the effort to enlist MRI in the diagnosis and treatment of psychiatric ailments is John Port at the Mayo Clinic in Rochester, MN. Port is a neuroradiologist who began his career by studying electrical engineering and computer science at MIT and later earned a PhD in cell biology and an MD from the University of Illinois. So he’s in a good position to research both basic MRI technology and its applications to medicine.

Port’s work on MRI could have broad application in psychiatry, but for now he is concentrating on his particular interest: bipolar disorder. Also called manic-depression, bipolar disorder is characterized by mood swings from wild exuberance to profound depression, with periods of stability in between. X-rays or conventional MRIs show no difference between the brains of people with bipolar disorder and those without it; medical journals are littered with failed attempts to use imaging to find distinctive signs of the disease.

Port thinks a lot of those attempts were scientifically flawed. “I have a list of pet peeves a mile long,” he says. “There are a million studies, but the patients might be on six different medications. So when you see something different, is it the meds? Or is something going on?” Another problem with many earlier studies, he says, is that they included too few patients. “You can’t tell anything from 10 patients. A lot of the research hasn’t been as rigorous as it should be.”

Indeed, despite years of work, neuroscientists still do not know what causes bipolar disorder, or exactly which parts of the brain are involved. That lack of knowledge has severely hampered the search for safer and more effective ways to treat the disease. The principal drugs for bipolar disorder, lithium and Depakote, have been around for decades.

Both were discovered by accident, when researchers trying to do something else noticed that the drugs eased the symptoms of patients with bipolar disorder. And though the drugs can be reasonably effective in some people, doctors have no idea how they work or which patients are most likely to benefit. In order to find better pharmaceuticals, researchers need to be able to target the exact mechanisms or structures involved in bipolar disorder.

Pinpointing the mechanisms could also lead to more accurate evaluation of the disorder. Often, diagnosis in psychiatry is done by a kind of trial and error, in which a psychiatrist makes an educated guess based on the behavior or self-reported symptoms of a patient, prescribes a medication, and sees whether or not it helps. If it doesn’t, the psychiatrist considers a different diagnosis and a different medication, until something begins to work.

“What psychiatrists need is some test that will give them the answer: this patient has the disease or doesn’t,” says Port. He and other researchers hope MRI scanners will offer the definitive diagnosis. And for those in the mental-health profession, that would change everything. “I’m dedicating the rest of my career to coming up with an imaging test that will help psychiatrists diagnose” bipolar disorder and other illnesses, Port says.

Tomorrow: A deeper look at the technologies of MRI spectroscopy and DTI.

Paul Raeburn’s most recent book is Acquainted with the Night, a memoir of raising children with depression and bipolar disorder.

Home page image courtesy of John Port.