The Effects of Diagnostic Ultrasound on the Connectome of the Central nervous system

Abstract

Although diagnostic ultrasound (US) is widely used and generally considered safe, earlier findings suggest that it may influence the dendritic arborization and spine morphology of CA1 neurons. US exposure has also been shown to exert a preventive effect on age-related hippocampal atrophy; particularly influencing the development of white matter tracts. This study focuses on whether repeated diagnostic-range US alters the morphology of selected key white matter tracts of the central nervous system connectome, specifically the fimbria (fimbria-fornix pathway) and the corpus callosum, including its genu. Time-mated pregnant CD1 mice, were exposed to 10-min sessions of diagnostic-range US, at embryonic day 18.5 and then once weekly during the first four postnatal weeks (five sessions total). Surviving offsprings were followed until 1 year of age, when brains were collected and imaged using high-resolution SkyScan 1272 micro-computed tomography (micro-CT) system. The longest diameter of fimbria and the thickness of the corpus callosum and its genu were measured and compared with age-matched sham-handled control. US-treated mice showed a significantly greater fimbria diameter (p = 0.0025, control 566.22 ± 53.09, US treated 725.81 ± 75.72), whereas the thickness of the corpus callosum and its genu did not differ significantly from controls (p = 0.18, control 279.30 ± 40.20, US treated 328.29 ± 57.75 and p = 0.52, control 384.89 ± 50.07, US treated 424.33 ± 57.12, respectively). Repeated diagnostic-range US did not induce generalized white-matter enlargement but produced a specific increase in fimbria size. Because fimbria carries hippocampal outputs, this finding suggests that some hippocampal efferent pathways may be more sensitive to ultrasound during development than interhemispheric callosal fibers. Together with our earlier observation on magnetic resonance imaging (MRI) in 1-month-old mice of ultrasound-related hippocampal changes, these data demonstrate that the structural effect may be long-lasting. The enlargement in the fimbria size could potentially enhance neuronal activity and hence improve memory and learning.