Behavioral effects of prenatal exposure to pulsed-wave ultrasound in unanesthetized rats

Abstract

The present experiment examined the developmental neurotoxicity of pulsed‐wave (pw) ultrasound in rats, using an exposure system designed to eliminate restraint or anesthesia from the exposure conditions. Pregnant Sprague‐Dawley CD rats trained to remain immobile in a water‐filled ultrasound exposure tank were scanned with 3‐MHz pw ultrasound at spatial peak temporal average intensities (ISPTA) of 0, 2, 20, or 30 W/cm2 on embryonic days 4‐20 for approximately 10 min/day. The data showed that such insonation produced no adverse effects on maternal weight gain or reproductive outcome, nor on the postnatal growth or survival of the offspring. No exposure‐related alterations in behavioral development were observed in the offspring of rats scanned with pw ultrasound during gestation. In addition, there was no consistent evidence of an ultrasound‐associated change in the adult offspring behaviors tested; i.e., no treatment effects were found on measures of locomotor activity, water maze learning, and acoustic startle reactivity. An effect on tactile startle was observed on some trials in the low exposure group male offspring, but this effect was neither dose dependent nor consistent with any other finding. Overall, these results indicate that the neurobehavioral development of rats was not altered by prenatal exposure to pw ultrasound at ISPTA levels of up to 30 W/cm2. © 1996 Wiley‐Liss, Inc.

How safe is it to use ultrasound in prenatal medicine? Facts and contradictions – Part 2 – Laboratory experiments regarding non-thermal effects and epidemiological studies

“…Fisher et al [34] performed a continuation of the study by Vorhees [25] and in contrast to many other authors, they performed their experiments on unanesthetized pregnant rats. The animals were not fixed and retained partial mobility in a temperate water bath.…”

“…Diese Intensität in Kombination mit der Beschallungsdauer übersteigt bei weitem die in der Pränatalmedizin maximal tolerierbare Exposition und würde schon rein rechnerisch mit der Gefahr irreversibler Hyperthermieschäden einhergehen. McClinic beschreibt allerdings, die Temperatur mittels Thermosonde überwacht und eine Steigerung von über 1,5°C ausgeschlossen zu haben.Fisher et al[34] hatten in Fortführung der Studie von Vorhees[25] (weiter vorn) und anders als viele andere Autoren Beschallungsversuche an nicht anästhesierten trächtigen Ratten durchgeführt. Dabei befanden sich die Tiere unfixiert und nur zum Teil ihrer Bewegungsfreiheit beraubt in einem temperierten Wasserbad.…”

Mechanical and Biological Effects of Ultrasound: A Review of Present Knowledge

“…In addition to the thermal effect of ultrasound, pulsed and continuous-wave ultrasound can affect reproduction and prenatal development of the embryo and fetus (Jensh and Brent 1999;Sikov 1986). Notable ultrasound effects such as increased malformation rates and weight changes have been observed in some studies, whereas others do not report any firm exposure-related effects in either dam or child (Brown et al 2004;Carnes et al 1991;Devi et al 1995;Fisher et al 1994Fisher et al , 1996Gu et al 2002;Devi 1992, 1995;Jia et al 2005;Karag€ oz et al 2007;Norton et al 1991;Oh et al 1999;Ryo et al 2001;Tarantal et al 1993). These studies used different endpoints, pregnancy ages, species and ultrasonic exposure conditions, making direct comparisons of results problematic.…”

“…These studies used different endpoints, pregnancy ages, species and ultrasonic exposure conditions, making direct comparisons of results problematic. No considerable treatment-related effects were observed on reproductive outcome or maternal weight during gestation, on viability or weight of offspring or on the morbidity of skeletal or visceral malformations when rats were exposed to 3-MHz continuous wave (Vorhees et al 1991(Vorhees et al , 1994 or pulsed (Fisher et al 1994(Fisher et al , 1996 ultrasound up to 30 W cm 22 (I SPTA ). Statistically considerable decreases in weight of offspring were observed after frequent exposure of cynomolgus macaques to ultrasound (at 7.5 MHz and I SATA 5 0.28-12 mW cm 22 ) Hendrickx 1989a, 1989b;Tarantal et al 1993); this effect occurred during the first 3 mo of life and not the subsequent 9 mo.…”