Fall 2003 Volume 16, Number 2	Following HIV's Dark Progress with Spectroscopy
	When the AIDS virus enters the brain, as it does in 90 percent of patients, it effectively slips into a black box. Sure, you can tell it's there a decade later if cognitive problems arise in patients or, in a smaller number, when the brain has failed to the point of dementia.
But what happens in between is hard to decipher. HIV trips biochemical cascades within glia and other resident cells. And researchers suspect the brain's perverted immune system periodically recruits new supplies of more resistant virus into the brain. Yet what triggers the process? How does dementia begin? And more important for patients, how can you tell if therapy in the brain is working? A newer technology should bring some answers. "Magnetic resonance spectroscopy (MRS) monitors specific molecules in living patients," says Martin Pomper, M.D., Ph.D. "It's noninvasive and lets us measure what we're tracking." Both Pomper, a neuroradiologist, and spectroscopy pioneer Peter Barker, Ph.D., have been testing the usefulness of MRS and MRSI (MRS imaging) in tracking disease. The former technique assays molecules in a small area of the brain. The latter maps that data on brain slices. Both methods, which use standard MRI scanners, are becoming routine in some neuro clinics. By measuring key molecules, they can, for example, tell whether a brain shadow is a tumor or inflammation. Or they can spot metabolic brain defects in children. But recent work at Hopkins centers on HIV. Pomper's team has imaged AIDS patients for more than three years, monitoring levels of several molecules that report on brain health. The marker N-acetyl aspartate, or NAA, for example, dips when neurons are injured or die. Choline is more of a biochemical scream: it rises with high membrane turnover, as in inflammation, and signals something seriously wrong. "Yet pointing our magnets at someone's head to say, 'This patient's got low NAA in frontal white matter' doesn't mean much," says Pomper. His team aims to relate the brain images both to patients' health and to levels of markers in their blood and spinal fluid that rise in an overactive immune system. It's akin to feeling a doorknob for heat when you suspect a fire in the hotel hallway. "We're pretty confident we'll be able to follow dementia with MRS," says Pomper, "as well as map the affected parts of the brain." A key part of the study goes one step farther, tracking AIDS patients on antiretroviral therapy. Early results suggest MRSI can show if drugs are working. Frontal lobe choline, for example, rises as it should with brain infection, then drops as therapy takes hold. Before long, Pomper begins another project linked to mental disturbance-depression. With luck, he'll be using spectroscopy to brain-image the sort of depression people get with autoimmune disease-noninvasively, while it happens. For information, call 410-433-4660. Dr. Barker is also with The Kennedy Krieger Institute.