The prolonged and frequent use of ultrasound on pregnant mice causes brain abnormalities in the developing mouse fetus, Yale School of Medicine researchers report August 7 in the Proceedings of the National Academy of Sciences.

\"Proper migration of neurons during development is essential for normal development of the cerebral cortex and its function,\" said Pasko Rakic, M.D., chair of the Department of Neurobiology and senior author of the study. \"We have observed that a small but significant number of neurons in the mouse embryonic brain do not migrate to their proper positions in the cerebral cortex following prolonged and frequent exposure to ultrasound.\"

Neurons in mammals multiply early in fetal development and then migrate to their final destinations following an inside-to-outside sequence. The destination defines the neurons\' connectivity and function. It has been reported earlier by others that abnormal cortical function may result when this process is grossly altered by genetic or environmental factors such as alcohol and drugs.

The study reported on August 7 is believed to be the first to look at the possible effect of ultrasound waves (USW) on neuronal migration in mice at a late stage of embryonic brain development, when the migratory pathways are the longest and may be most vulnerable. The Yale team injected more than 335 fetal mice at embryonic day 16 with special markers to track neuronal development. Exposure to USW for 30 minutes or longer caused a small but statistically significant number of neurons to remain scattered within inappropriate cortical layers and/or in the adjacent white matter.

\"The magnitude of dispersion of labeled neurons was highly variable but increased with duration of exposure to ultrasound waves,\" Rakic said. \"These findings suggested the desirability of further work in this area. We do not have any evidence ourselves that USW cause behavioral effects in mice or have any effect on the developing human brain.\"

\"Therefore,\" he continued, \"I want to emphasize that our study in mice does not mean that use of ultrasound on human fetuses for appropriate diagnostic and medical purposes should be abandoned. On the contrary: ultrasound has been shown to be very beneficial in the medical context. Instead, our study warns against its non-medical use. We intend to conduct further research, which will focus on non-human primates, to see if a similar effect is occurring in the developing larger brains, which are more similar to humans. Those upcoming studies should give us information that will be more directly applicable to uses of USW in humans.\"

The National Institute of Neurological Disorders and Stroke of the National Institutes of Health supported the study.

C-authors include Eugenius Ang Jr., Vicko Gluncic, Alvaro Duque and Mark Schafer of Yale.

PNAS (early edition August 7, 2006)

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