Sep. 9, 2002 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. 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.
Reference: Eswaran H, Wilson JD, Preissl H, Robinson SE, Vrba J, Murphy P, Rose DF, Lowery CL. "Magnetoencephalographic recordings of visual evoked brain activity in the human fetus." The Lancet, Vol. 360, No. 9335, pp. 779-780.
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