Brain Imaging: The Future Is Now

by Guy McKhann, M.D.

December 7, 2007

One of the research areas the Dana Foundation supports is the application of imaging techniques to the understanding of normal brain functions and brain diseases. Ever-changing advances in imaging techniques keep this program vibrant. The accomplishments of imaging come in various forms.

Structural imaging

The first form of imaging to appear on the scene was structural imaging—the demonstration of the structure of the brain, originally by computerized axial tomography, or CAT, and then by magnetic resonance imaging, or MRI. Structural imaging had immediate clinical applications providing identification of a brain tumor, a stroke, multiple sclerosis or the shrinkage of the brain associated with Alzheimer’s disease. One could also judge whether a brain was developing normally.

Several of our articles indicate newer uses of structural imaging. Before commenting about those stories, it is worthwhile to distinguish between two types of studies: cross-sectional studies and longitudinal studies.

A cross-sectional study compares groups within populations, such as a group of 30-year-olds with groups of 50- and 70-year-olds. Almost all studies of aging are done in this way.

Longitudinal studies examine the same individuals over time. If you wanted to longitudinally study an aging population from 40 years to 80 years, you better have several things: patience, a history of longevity in your family, and a “day job,” because you might not have much data to present for many years. But it can be done!

Arthur Toga of UCLA did this over 14 years, using his own kids starting when they were 6 and continuing until they were 20. Their story is profiled in the Wall Street Journal article “Researcher Contributes Unique Family Album: Scans of Kids’ Brains." Toga has demonstrated that the brain continues to develop much longer than previously thought. So when someone asks your teenager, “When are you going to grow up?” he can answer, “My brain still has a way to go!”

Maybe someday we will also have brain images of our kids or grandchildren in the family album. You think this is science fiction, but you wouldn’t have predicted that you would have an ultrasound of your fetus on the refrigerator, either.

Structural imaging is also used to compare the normal with the abnormal. A group at the Massachusetts General Hospital compared scans of people with and without migraine and found that parts of the cortex of the brain were thicker in “migraineurs.” What isn’t clear is whether this is related to the cause of migraine or to the effect. This cross-sectional study is featured in the BBC News article “Migraine Brains ‘Are Different.’ ”

A logical extension of this study would be to start with those at risk for migraine, or right after the first attack, and perform longitudinal studies to determine if these changes in cortical thickness pre-exist or develop.

That’s what a group of investigators, led by those at the National Institute of Mental Health, did when they compared 223 people with attention-deficit/ hyperactivity disorder (ADHD) with 223 without. This study appears in the Associated Press article “ADHD Kids’ Brains Develop More Slowly.” Subjects were examined at three-year intervals, two to four times.

Using elaborate computational techniques, the researchers determined the age at which the maximal thickness of the cortex occurred. The children with ADHD showed a delay of two to three years compared with the normally developing children. This difference was particularly noticeable in the frontal regions of the brain, which are involved in planning and control of actions—the so-called executive functions.

Thus ADHD is a problem of maturational delay. Many kids catch up, some don’t. Understanding why is the next step.

Cellular and molecular imaging

Working on a smaller scale than structural imaging, cellular imaging determines the composition and functions of brain cells. We used to think that a person was born with all the nerve cells he or she would ever have. We now know that idea is wrong and that we continue to add new nerve cells through out our lives, albeit only in certain parts of the brain. What has been missing is any way to see what is happening in the human brain.

Mariana Maletic-Savatic and her colleagues at Stony Brook University have developed a way of demonstrating a marker—a substance found in the stem cells that will become nerve cells, but not found in mature brain cells. To image this substance they teamed up with an investigator in the electrical engineering department, Petar Djuri, to use a different form of magnetic resonance imaging called magnetic resonance spectroscopy—a technique that determines the chemical composition of tissues.

Adapting this methodology to the imaging of the hippocampus, the part of the brain that is involved in memory processing, the researchers demonstrated for the first time the presence of new nerve cells. Their story is recounted in the Scientific American story “The Birth of a Brain Cell: Scientists Witness Neurogenesis.”

If this finding holds up, we could have a valuable tool for determining the dynamics of new nerve cell formation in normal memory, altered memory as in Alzheimer’s disease, and in the response to medications.

I am often asked, “What’s driving the advances in brain sciences?” There are many possible answers, but clearly brain imaging is one of them.

Guy McKhann, M.D., is professor of neurology and neuroscience at the Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore. He serves as scientific consultant for the Dana Foundation and scientific advisor for Brain in the News.