University of Iowa researchers have developed an MRI-based method to detect and monitor pH changes in living brains. The image shows MRI brain scans of human subject breathing air (left) or air containing 7.5% carbon dioxide (middle). The difference between the two scans (shown right) shows increased brain acidity in red caused by carbon dioxide inhalation as measured by the new MRI-based strategy. Credit: Vincent Magnotta, University of Iowa |
University
of Iowa neuroscientist John Wemmie, M.D., Ph.D., is interested in the
effect of acid in the brain. His studies suggest that increased acidity
or low pH, in the brain is linked to panic disorders, anxiety, and
depression. But his work also suggests that changes in acidity are
important for normal brain activity too.
“We
are interested in the idea that pH might be changing in the functional
brain because we’ve been hot on the trail of receptors that are
activated by low pH,” says Wemmie, a UI associate professor of
psychiatry. “The presence of these receptors implies the possibility
that low pH might be playing a signaling role in normal brain function.”
Wemmie’s
studies have shown that these acid-sensing proteins are required for
normal fear responses and for learning and memory in mice. However,
while you can buy a kit to measure the pH (acidity) of your garden soil,
there currently is no easy way to measure pH changes in the brain.
Wemmie
teamed up with Vincent Magnotta, Ph.D., UI associate professor of
radiology, psychiatry, and biomedical engineering, and using Magnotta’s
expertise in developing MRI (magnetic resonance imaging)-based brain
imaging techniques, the researchers developed and tested a new,
non-invasive method to detect and monitor pH changes in living brains.
According
to Wemmie, the new imaging technique provides the best evidence so far
that pH changes do occur with normal function in the intact human brain.
The findings were published May 7 in the Proceedings of the National Academy of Sciences (PNAS) Early Edition.
Specifically,
the study showed the MRI-based method was able to detect global changes
in brain pH in mice. Breathing carbon dioxide, which lowers pH (makes
the brain more acidic), increased the signal, while bicarbonate
injections, which increases brain pH, decreased the MRI signal. The
relationship between the signal and the pH was linear over the range
that was tested.
Importantly,
the method also seems able to detect localized brain activity. When
human volunteers viewed a flashing checkerboard—a classic experiment
that activates a particular brain region involved in vision—the MRI
method detected a drop in pH in that region. The team also confirmed the
pH drop using other methods.
“Our
study tells us, first, we have a technique that we believe can measure
pH changes in the brain, and second, this MRI-based technique suggests
that pH changes do occur with brain function,” Magnotta says.
“The
results support our original idea that brain activity can change local
pH in human brains during normal activity, meaning that pH change in
conjunction with the pH-sensitive receptors could be part of a signaling
system that affects brain activity and cognitive function,” Wemmie adds
A new way to view brain activity
Importantly, this technique may also provide a new way to image the brain. Currently,
functional MRI (fMRI) measures brain activity by detecting a signal
that’s due to oxygen levels in the blood flowing to active brain
regions. The UI team showed that their method responds to pH changes but
is not influenced by changes in blood oxygenation. Conversely, fMRI
does not respond to changes in pH.
“What
we show is our method of detecting brain activity probably depends on
pH changes and, more than that, it is distinct from the signal that fMRI
measures,” says Wemmie. “This gives us another tool to study brain
activity.”
pH and brain function
Wemmie’s
previous studies have suggested a role for pH changes in certain
psychiatric diseases, including anxiety and depression. With the new
method, he and his colleagues hope to explore how pH is involved in
these conditions.
“Brain
activity is likely different in people with brain disorders, such as
bipolar or depression and that might be reflected in this measure,”
Wemmie says. “And perhaps most important, at the end of the day; could
this signal be abnormal or perturbed in human psychiatric disease? And
if so, it might be a target for manipulation and treatment?”
In
addition to Wemmie and Magnotta, the UI team included Hye-Young Heo,
Brian Dlouhy, Nader Dahdaleh, Robin Follmer, Daniel Thedens and Michael
Welsh.
The
work was supported by the McKnight Endowment Fund for Neuroscience, the
Dana foundation and a UI Clinical and Translational Science Award.
Source: University of Iowa Health Care
