NEW DEVICE DETECTS FETAL BRAIN RESPONSE TO LIGHT

May Help Prevent Brain Damage

For years, doctors who work in maternal and fetal medicine
have had no way to detect brain activity in unborn
children. Now, for the first time, researchers using a
unique scanning device have shown that they can detect
fetal brain activity in response to flashes of light
transmitted through the mother's abdomen. With refinement,
this technique may help physicians detect and prevent fetal
brain damage resulting from maternal hypertension,
diabetes, and other conditions. The work was supported by
the National Institute of Neurological Disorders and Stroke
(NINDS) and appears in the September 7, 2002, issue of "The
Lancet." (1)

The study is one of the first tests of a new device
designed to study maternal and fetal physiology, including
fetal brain activity, using magnetoencephalography (MEG) of
the womb. It also is the first MEG study to use light,
rather than pulses of sound, to stimulate the fetus.

"Though this work is preliminary, it is a promising
indication of how MEG may help researchers understand the
fetal brain," says Giovanna Spinella, M.D., a pediatric
neurologist at NINDS.

The new device, called SARA, was conceptualized by Curtis
L. Lowery, M.D., of the University of Arkansas for Medical
Sciences and developed by CTF Systems Inc., of Port
Coquitlam, British Columbia, Canada. NINDS helped to fund
development of the device, which is the first of its kind
in the world. SARA stands for SQUID Array for Reproductive
Assessment. SQUID is an acronym for Superconducting
Quantum Interference Device, a method developed to detect
tiny fluctuations in magnetic fields using a superconductor
cooled by liquid helium.

Previous studies have shown that maternal hypertension,
diabetes, pregnancy with two or more babies at once, and
many other conditions can lead to hypoxia (lack of oxygen)
that can damage the fetal brain. Prenatal infections,
smoking, and other problems also can interfere with normal
brain development. Structural problems in the fetal brain
can often be detected using magnetic resonance imaging
(MRI). However, until recently it has been impossible to
directly assess brain activity in an unborn child.
Researchers have now begun to experiment with MEG and
another type of brain scan, called functional MRI, in order
to overcome this problem. Both techniques work by
measuring tiny magnetic field changes that result from
brain activity.

"To develop therapies, you need to be confident in
intrauterine diagnosis," says Dr. Lowery, who led the
study. Currently available tests, such as fetal heart-rate
monitors, have a high false positive rate, meaning that
they often indicate a problem when there really isn't one.
Using SARA could help to determine if a baby is really at
risk, enabling doctors to better decide when treatments
will be beneficial, Dr. Lowery says. Doctors might be able
to prevent brain damage by delivering the baby before term,
by cooling the baby's head after delivery, or someday even
by using neuroprotective drugs, he adds.

In the study, Dr. Lowery and his colleagues tested SARA
with 10 fetuses that had a gestational age of 28 - 36 weeks
and no known risk factors for brain damage. Fetuses whose
eyes were more than 3 centimeters from the maternal skin or
whose heads were facing down or away from the mother's
abdomen were excluded from the study. The expectant
mothers sat upright on the SARA machine and leaned forward
into a concave array of 151 sensors that surrounded the
abdomen. The researchers then used a fiber-optic cable to
deliver light pulses to the outside of the mother's abdomen
while they recorded MEG data. The light used was about 11
times less intense than sunlight on a bright day.

When they screened out signals from the maternal and fetal
heart beats, the researchers found that 4 of the 10 fetuses
had measurable brain responses to the light pulses. The
time between the light pulses and each fetus's response
decreased with increasing gestational age. It is unclear
why 6 of the fetuses did not respond to the stimulus, Dr.
Lowery says. They may have been asleep during the test, or
the position of their heads may have prevented them from
seeing the light. He believes researchers may get better
results if they test the same fetus repeatedly.

Much more testing is needed to define what types of
responses indicate normal and abnormal brain activity in
fetuses at different gestational ages, Dr. Lowery says.
Unborn babies with specific kinds of brain damage may have
no response to certain types of stimuli, or a delayed
response. The researchers now plan to test larger numbers
of fetuses to determine what types of brain responses may
indicate a problem. They also plan to test babies born
with abnormalities to try to determine how their responses
differ from those of other babies. A special "cradle"
adapter allows the researchers to scan newborn babies using
SARA.

While this study showed that visual stimulation can
activate the fetal brain, other types of stimulation may
also be used with SARA. These might include auditory
stimulation (such as pulses of sound or exposure to a
mother's voice), vibration, or magnetic stimulation. Using
several different kinds of stimuli may yield more
conclusive results than a single test, because different
types of stimuli activate different parts of the brain, Dr.
Lowery says. The researchers also are investigating
whether SARA can detect baseline brain activity in the
fetus when no special stimulus is present.

In addition to improving clinical care, SARA may be useful
as a research tool to investigate brain development in the
womb. Data from such tests might ultimately lead to new
insights about the causes of cerebral palsy and other
developmental disorders, and to ways of preventing those
disorders. SARA could be used with a visual stimulus as
early as the 24th week of pregnancy, when the eyes have
matured and the cortex is fully connected to the lower
brain regions, according to Dr. Lowery.

The researchers are now planning to develop and test better
light stimulators, such as lasers, and to perform serial
brain scans, in which they examine a fetus's responses over
a period of time. Since SARA also can detect the fetal
heartbeat, uterine activity, and other physiological
factors that may influence a healthy pregnancy outcome, it
ultimately could be used in a variety of clinical tests,
the researchers say.

The NINDS is a component of the National Institutes of
Health in Bethesda, Maryland, and is the nation's primary
supporter of biomedical research on the brain and nervous
system.