but lower penetration, hence the need to be closer to the organs being examined. Diagnostic ultra­sound is not continuous but pulsed. There are pulses separated by silent intervals. The number of pulses occurring in 1 s is the pulse repetition fre- quency (PRF). The fraction of time that the pulsed ultrasound is on (duty factor) is very important from a potential bioeffect aspect. When the PRF increases, so does the duty factor. Since the ultra­sound wave is sinusoidal, there are alternating periods of positive and negative pressure which allow the wave to propagate through tissues by means of particles motions. The speed of propaga­tion is related both to the beam and several of the tissue properties. The average speed of sound propagation in biological tissues is estimated at 1,540 m/s. When pressure is exerted on the resist­ing insonated tissue, work is produced. The ability of the wave to do this is its energy (in joules), and the rate at which the energy is transformed from one form to another is the power (in watts or mil- liwatts, mW). When expressed as a function of area unit (in cm 2 ), this is intensity (generally in mW/cm 2 ). Bioeffects are conventionally related to the acoustic intensity. As stated above, pulses of energy are intermingled with periods where no energy is emitted. When describing an ultrasound wave, several parameters can be described in rela­tion to time or space. By combining peak and aver­age values in time and space, six intensities can be defi ned. The spatial peak-temporal average ( I

The growing embryo/fetus is particularly sensi­tive to external infl uences. For instance, certain medications or drug of abuse taken by the preg­nant woman, exposure to X-rays, and elevated temperature, secondary to infectious diseases, are all known teratological agents [ 69 ]. This is espe- cially true in the fi rst 10–12 weeks of gestation. Gestational age is thus a vital issue when dealing with possible bioeffects: milder exposure during the preimplantation period can have similar con­sequences to more severe exposures during embryonic and fetal development and can result in prenatal death and abortion or a wide range of structural and functional defects.

and no consistent increase in mortality was observed nor did the authors detect any other abnormalities. Evidence, however, of the possi­bility of ultrasonically produced embryolethal effects during organogenesis has been described [ 80 ]. Sikov and colleagues exposed an exterior- ized rat uterus to various frequencies, some of them clinically relevant (0.8, 2, and 3.2 MHz), at day 9 and evaluated the offspring at day 20 [ 81 ]. The exposure was performed at different inten­sity levels, with exposure times at 5 or 15 min. No effect on fetal weight was observed, even at spatial average intensities as high as 30 W/cm 2 , but prenatal mortality at 15–20 W/cm 2 (spatial average) clearly increased with increasing expo­sure time. The cause of this was ascribed to a thermal mechanism. A recent controversial study looked at neuronal migration in rat pups after maternal exposure to ultrasound [ 75 ]. Neurons of the cerebral neocortex in many animals (includ­ing humans) are generated during fetal life in the brain proliferative zones and then migrate to their fi nal destinations by following an inside-to­outside sequence. In Ang’s experiment neurons generated at embryonic day 16 and destined for the superfi cial cortical layers were chemically labeled in over 335 rats. A small but statistically signifi cant number of neurons failed to acquire their proper position and remained scattered within inappropriate cortical layers and/or in the subjacent white matter when exposed to ultra­sound for a total of 30 min or longer during the period of their migration. The magnitude of dis­persion of labeled neurons was variable but increased with duration of exposure to ultrasound (although not linearly, with the most extended exposure yielding less effect than the one imme­diately lower). It is not clear whether a relatively small misplacement, in a relatively small number of cells that retain their origin cell class, is of any clinical signifi cance. It is also important to note that there are several major differences between the experimental setup of Ang et al. and the clinical use of ultrasound in humans [ 8 ]. Most noticeable was the exposure duration, up to 7 h in Ang’s setup, and the fact that scans were per­formed over a period of several days. Furthermore, embryos received whole-brain exposure to the

has to be kept in mind for ultrasound examina­tions in which an endocavity (e.g., endovaginal) transducer is used, although in experiments, the effects on the fetus seemed to be negligible after 2 cm penetration [ 78 ].