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FEATURE STORY 73
for a pin drop in a thunderstorm,” Port says. Each proton
has a magnetic �eld that points in a certain direction, as
the earth’s does. When the MRI is turned on, its magnet
aligns the protons’ magnetic �elds in the same direction.
Bursts of radio frequency energy temporarily knock some
of the protons out of alignment. When the protons snap
back into place, they release energy, generating a minuscule
signal that the MRI’s detectors can pick up. By �ipping the
protons di�erent ways and measuring various properties
of those �ips, including the time they take, researchers can
identify various tissues and chemicals in the brain.
Using MRI spectroscopy, Port can measure levels of
chemicals such as n-acetyl aspartate, which is found only
in neurons, or glutamate, which stimulates ner ve-cell activ-
ity. When Port used the technique across many areas of
the brain in bipolar patients and compared the results to
those from healthy controls, he came up with a chemical
�ngerprint that seemed to be an indicator of bipolar dis-
order. “When we compared all the bipolar patients in any
mood state with their matched normal control subjects, we
found that two areas of the brain were signi�cantly di�er-
ent,” Port says. Port and his team also identi�ed changes
in many regions of the brains of people with bipolar dis-
order that indicated whether they were in a manic state or
depressed. “We found a chemical measure of the mood
state,” he says.
So has Port found the long-sought diagnostic test for
bipolar disorder? Does his chemical �ngerprint reliably
identify people who have bipolar disorder and exclude
those who don’t?
Maybe, but he can’t be sure yet. “We think we’re on to
something good,” he says, but “we have to check it and make
sure it will be clinically useful.” It’s a question of trying the
technique with enough patients to be sure that it is statisti-
cally valid—that it won’t produce too many false positives or
false negatives. It doesn’t have to be perfect, but it has to be
good enough to add useful information to what psychiatrists
can discern through their traditional methods of diagnosis,
interviews, and analyses of patient histories. If Port is cor-
rect, however, and the technique proves itself, it would be a
landmark in psychiatric research: a diagnostic test for bipolar
disorder. And if the technique works with bipolar disorder
it could be adaptable to other psychiatric illnesses
Port and others are also experimenting with di�usion
tensor imaging. DTI measures water di�usion in the brain.
Water �ows through the brain as it does anywhere else—
along the path of least resistance. In the brain, that’s along
the axons, the neurons’ long tails, which convey electrical
signals to other neurons. (It’s from the fatty, white insula-
tion that surrounds most axons that “white matter” takes
its name; the rest of the neuron, and uninsulated axons,
together constitute “gray matter.”) Port is just beginning to
research the technique. But eventually researchers will be
able to use “DTI clinically to look for diseases that inter-
fere with white matter—amyotrophic lateral sclerosis [Lou
Gehrig’s disease] and schizophrenia,” Port says
The techniques Port is studying, if they prove successful,
will be used in diagnosing people already showing signs of
mental illness. But what about others who are predisposed
to problems but have not yet begun to exhibit symptoms?
Can the MRI technology help to �nd these people so that
they can be helped before symptoms appear?
At Columbia, Peterson is trying to answer that question.
He and collaborators are among the �rst to scan the brains
of premature infants—sometimes within days of their birth.
The aim is to catalogue the types of brain abnormalities
they discover and to devise ways to inter vene earlier than
ever before to try to correct or compensate for them
Peterson �rst became interested in the complications of
premature birth about 10 years ago, when he was beginning
his psychiatric research at Yale University. He had discovered
Mayo Clinic researcher John Port is using magnetic resonance
spectroscopic imaging to look for physiological changes associ-
ated with bipolar disorder. Port ﬁrst stimulates a localized region
of the brain (white box), then divides the brain into 3-D sections
(gray lines) called voxels. Each voxel contains information on con-
centrations of metabolites in its corresponding section of brain tis-
sue. The studies have so far revealed that there are characteristic
concentrations of metabolites in patients with bipolar disorder.
COURTESY OF JOHN PORT
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