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The New Mouse Study

Recently an article has been published with findings of ultrasound effects on neuronal migration in fetal mice (10).  The results have been largely dismissed by the ultrasound establishment, in part because the entire mouse fetus, including the brain, was exposed during the experiment and there was a threshold duration of 30 minutes for the effect to be documented. This is far longer than any particular area of the much larger human brain would be exposed to in a standard screening second trimester examination, and there are thicker cranial bones surrounding the brain than in the fetal mouse, causing attenuation of ultrasound.  Two points in response: (A) The derated MI 0.66 used in the fetal mice study was in the usual diagnostic range, but the  time averaged (Ispta) levels were much lower -   0.6 mW/cm 2 allowing for attenuation; compare with the value in reference 2 of 144 mW/cm 2  (32).  The low value in this experiment may be explained in part by the ultrasound probe used, which has three transducers with different frequencies mounted on a rotating head.  Only one of these was selected, implying that 30 minutes of apparent exposure should be divided by three to arrive at true exposure duration - about 10 minutes.  This sort of multifrequency mechanical probe arrangement is not used clinically in current-generation scanners which “sweep” electronically. (B)  Screening ultrasound at 11-13 weeks for Down’s syndrome detection is increasingly promoted. Exposure of the smaller fetus at this stage of pregnancy, including the much of the, brain, may be quite lengthy: “A minimum of 20 minutes was reserved for the assessment” (11).  Cranial bones are less dense at this stage. 

Considerable caution must be exercised in assessing the results of this study, which needs to be replicated by others and with equipment relevant to current clinical practice.  Humans are not mice. Even a somewhat skeptical commentary (12), however, was tuned to clinical concerns: “Application of the principle of as low as reasonably achievable (ALARA) in US is recommended by practice guidelines and is a responsible guide for all fetal and pediatric imaging studies.  This principle holds that the goal of a study is not an image with the maximal quality achievable but one that is sufficient to make a diagnostic judgment with the least possible exposure.”

If the experimental finding is a true ultrasound effect, it is occurring at a level below heating or cavitation.  Speculations include acoustic streaming, shear effects, and radiation force (10, 12).

Studies from Norway and Sweden have raised the possibility that fetal exposure to diagnostic ultrasound may have some effect on subsequent handedness.  A review and critique of these has been published (1).  An interesting demonstration of fetal stimulation (increased movement and heart rate) by exposure of the fetal head and ear regions to simultaneous imaging and pulsed Doppler involving a small number of subjects has been reported from the Mayo Clinic (2).  The mechanism is thought to represent a response to repeated pulses impinging on the fetal ear.  While diagnostic ultrasound itself uses frequencies well above the hearing range, the pulses of ultrasound energy are delivered with a repetition rate that is in the hearing range; this is a biological effect on the fetus unrelated to heating or cavitation.  Like the authors of this 2001 article, I hoped to see this experiment repeated with a range of exposure conditions, and also with larger numbers of subjects.  A PubMed search indicates that this has not yet happened.

The use of “low-dose” therapeutic ultrasound for fracture healing has already been noted in section 3.  Specialized diagnostic ultrasound has been shown to have a therapeutic role in some stroke situations by helping thrombolytic treatment for blood clots involving the middle cerebral artery; this made the grade to publication in the New England Journal of Medicine (13) with commentary and mechanism speculation (14).  The device was different from those used in fetal scanning, there was a deplorable absence of ultrasound intensity measurements/calculations and the duration of exposure was beyond most fetal situations, but the point remains that ultrasound exposure in the diagnostic range of intensities can have demonstrable biological effects. See Miscellaneous Items: Update July 2008 #2