New dynamic imaging techniques provide a deeper look at Alzheimer's and schizophrenia (excerpt)

Schizophrenia Update, October 2003


By Robert Adler, Globe Correspondent, 5/6/2003

Paul Thompson, the UCLA neuroscientist whose team created these first-ever sequences of a disease engulfing the living human brain, sees [new images they've captured on the disease process of schizophrenia and alzheimers] as a significant step toward earlier diagnosis, more effective treatment, and -- eventually -- prevention or cure of brain-destroying diseases.

Thompson, a 31-year-old British emigrant, is unabashedly excited about his team's accomplishments: ''The tools from our group are opening really new windows on what's happening inside the brain.'' They give researchers a powerful way to test new medications and lets doctors diagnose Alzheimer's and other dementias earlier and more accurately. That should give more patients an early start on medications that can at least slow the ravages of these diseases.

Like faces, no two brains are alike. As a result, it's extremely difficult to compare diseased and healthy brains or track changes over time. That's the problem Thompson and his team solved. By morphing ordinary MRI scans onto a standardized brain, they can pool scans from multiple patients without blurring the picture. They can then sequence those standardized images into revealing movies. And, crucially, they can quantify changes with great precision. ''We can code normal human variation,'' he said, ''and still be exquisitely sensitive to abnormal changes.''

As a result, Thompson's group has been able to study diseases such as Alzheimer's and schizophrenia as never before. ''With this kind of imaging, you can see a lava flow of destruction as more and more brain tissue is engulfed,'' Thompson said. ''You can see exactly which areas are losing tissue, when, and how fast.''

Thompson first applied these new tools to schizophrenia....In 2001, Thompson's group produced the first time-lapse images revealing a wave of tissue loss rolling across the brains of schizophrenic children. They utilized high-resolution MRIs of more than 1,000 children scanned every two years since 1992 by Judith Rapoport and colleagues at the National Institute of Mental Health. Thompson's group detected the first flicker of the disease in a small part of the parietal cortex, above and behind the ears.

Over five years, Thompson saw a ''pervasive, unrelenting wave of tissue loss that swept forward like a forest fire,'' eventually engulfing the sides and front of the brain. By 18, the teenagers had lost 25 percent of their gray matter in certain brain areas.

''Seeing that wave of tissue loss in schizophrenia was a huge surprise,'' Thompson said. The pattern matched the drumbeat of schizophrenia's active and passive symptoms -- hallucinations, delusions and bizarre thinking followed by flattened emotions, depression and withdrawal.

The images are disturbing but valuable. They've pushed Thompson toward the theory that schizophrenia is a disrupted version of normal brain development.

Teenagers' brains normally undergo extensive ''pruning'' in which 1 percent of the gray matter disappears every year, more in some areas. Because schizophrenia typically strikes during this process, Thompson sees it as ''an exaggeration or derailment'' of normal pruning -- like a gardener gone wild.

His finding that schizophrenia takes up to seven years to engulf the brain highlights the need for early diagnosis and treatment. It also makes finding drugs that may salvage young people's brains even more vital. ''There is a window of opportunity to step in and oppose the disease,'' he said.

Dynamic brain imaging should also speed up the search for genes that predispose people to specific brain diseases. We know they're there. Siblings and children of schizophrenics have one chance in 10 of developing the disease -- 10 times the average risk. A half-dozen genes already have been linked to Alzheimer's, with more to come. It is much easier to match suspect genes to specific patterns of tissue loss than to shifting, hard-to-measure symptoms.

Thompson's movies can be viewed at



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