Proposing that prenatal ultrasound is a potential teratogen sounds like pseudoscience to most people, I realize this. Hell, when my partner came to me with the idea even I thought he’d gone round the bend. But he really wanted us to review the literature and see if this crazy notion could have any foundation at all. Prenatal ultrasound is after all a growing clinical epidemic and the Rakic team out of Yale had published a paper back in 2006 that found changes in the brains of prenatally exposed mice, so why not? [1]

With my reservations in hand, I started scanning the literature. At first all the early safety studies from the ’70s and ’80s seemed to say the same thing: “No deleterious changes following exposure.” Again and again I came across the same types of studies, many epidemiological. After awhile and in frustration, I set the searches aside because the literature at first glance really seemed to suggest that ultrasound was relatively safe, and the occasions in which differences did arise, such as low birth weight, they eventually righted themselves. So not much to go on.

After a nice hiatus investigating other things, I ran across an article that showed that when osteoblasts, fibroblasts, and monocytes were subjected to ultrasound in vitro (in a petri dish), exposure stimulated the production of interleukin-8, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF), each of which acts as growth factors on these and nearby cells [2]. That same group later found that osteoblasts under similar levels of exposure release nitric oxide and prostaglandin E2, both of which are known to have growth-inducing effects on bone [3].

Even though we’re talking bone and not my primary focus, brain, these results truly intrigued me. Unfortunately, one can’t be certain from such an experiment that the same would be found in vivo (in life) as opposed to a petri dish and whether such effects occur across cell types. But the fact that the effect was real ignited my curiosity and I was primed to continue my searches into the biophysical mechanisms of ultrasound. It hasn’t been easy because the research is spread across numerous professional disciplines, but here’s a basic rundown of my literary travels:

Ultrasound is exactly that, “ultra” and “sound”. It’s an auditory waveform that occurs above the upper limit for human hearing. Like all sounds– and as is implied by the term “waveform”– this flow of sound pressure occurs in waves, called compression and expansion half-cycles. All that simply means is that the materials that are hit by this sound undergo alternations of a compression of their materials followed by an expansion, kind of like an accordion. This is one of the things that makes ultrasound potentially dangerous, dependent on the level of intensity of the soundwave and the duration of exposure.

The act of bubble or cavity formation within a liquid upon ultrasound exposure is called cavitation. The term cavitation is particularly used to refer to the implosion of a gaseous bubble under pressure within a liquid, although this is more specifically known as transient cavitation. Stable cavitation is the formation of bubbles which remain relatively stable in the liquid medium. In pure water, bubbles form at more than 1,000 atmospheres of pressure, which is to say that if you were to take pure water and subject it to even the highest intensities of diagnostic or prenatal ultrasound, bubbles would not form because the intensity is far too low. But not so for biological tissues. As occurs with almost every solid within a liquid (e.g., cells), small gaseous pockets hide within crevices. The pre-existence of such bubbles essentially lowers the threshold for cavitation within biologic tissue compared to pure water because gaseous cavities, though extremely small, are already present. When subjected to the force of ultrasound, these bubbles undergo expansion with the expansion half cycles and compression with the compression half cycles. Just picture taking a balloon, blowing it up, then sucking in a little of the air and seeing it contract a little bit, and repeat this procedure over and over again. In this analogy you are the ultrasound wave, the force driving expansion and contraction. The main problem is that with each subsequent cycle, the bubble compresses less and less, so over time the size of it grows until at which point, much like when that balloon is filled till it pops, the surface area of the bubble can no longer withstand the pressure. In the case of a bubble in liquid, it implodes and the surrounding water rushes in, meets with the gases once trapped in the bubble, triggering a violent chemical reaction which produces an extraordinary local rise in temperature– a temperature close to that of the surface of the sun [4]. Thankfully, the rapid cooling rates of the surrounding medium (on the order of 109 ⁰C·s-1) virtually assure that for a single occurrence the temperature of surrounding tissues rises insignificantly. The problem arises when transient cavitation occurs more frequently in a local tissue such that the rapidity of cooling is not as efficient which can cause thermally-induced tissue damage.

These little bubbles can also cause other problems aside from temperature increase. As you might imagine, when a bubble implodes it can create a considerable force of pressure in the surrounding medium such that nearby cells may be hit with high pressure water jets. This can also occur, though in a gentler fashion, by stable cavitation in which the bubble doesn’t implode but merely oscillates next to or within a cell, creating a variety of forces and pressures against the outer membrane and within the cell itself. In a worst case scenario, the jets of water may fatally damage the membrane and internal structures of cells, leading to cell death. In a less deadly scenario, the water jet may poke transient holes through the outer membrane of the cell which allows into the cell many communicating molecules such as sodium, calcium, and various proteins. This inward rush of calcium, for instance, can activate many downstream pathways involved in cell repair, cell growth, and even alter cell-to-cell communication, such as in the case of neurons. Did you know in fact that ultrasound is used transcranially (across the skull) to elicit activity of target neurons? [5]

So what harm can a little calcium do? Well, if it doesn’t kill off the cell through calcium cytotoxicity, the fact that many of these extracellular molecules are normally used in a controlled way for cell-to-cell communication essentially feeds cells the wrong messages and could feasibly alter the development of cells permanently, especially concerning stem cells, progenitors, or immature cells which may pass down these alterations through further generations.

Previous in vitro studies have also found that ultrasound is capable of promoting chromosomal breakages in DNA, although there isn’t currently evidence to suggest the same severity is found in vivo within diagnostic and prenatal intensity ranges so this may be an effect particular to cell cultures [6]. But it does beg the question what ultrasound exposure may be doing to the cellular contents within exposed cells. Poking transient holes through membranes, jostling the cell’s internal contents, disturbing its general physiology, and if exposure occurs for a long enough duration, the greater the likelihood of cavitation, deadly jets of water, and thermally-induced damage.

Think of it: You subject cells to increased water pressure, and if the duration is long enough the threshold for transient cavitation may be reached. The potential for ultrasound’s teratogenicity is considerable and, in this scientist’s opinion, research has not been thorough enough to rule out possible dangers. Consider the ultrasound parties which are becoming all the rage or the keepsake ultrasounds parents are having done to “start the family photo album early”,– or what about the doppler ultrasound fetal heart rate monitors that parents can use unsupervised in their own homes on a daily basis? And that’s not even addressing the issues of poor technician education or the staggeringly high rates of malfunctioning ultrasound equipment used in everyday clinical practice [7, 8]. Ultrasound regulations are dismal in this country and may unknowingly be turning a useful tool into a teratogen.

I want you to think about this: The image below is a pump which has been degraded by transient cavitation stimulated by ultrasonic waves. If you have enough force, this is what occurs to metal. Just think what could be happening to a developing fetus. Admittedly, this image is meant to scare you. And while the intensity levels and duration of exposure which a fetus endures are by no means comparable to what this water pump has gone through, it’s the same basic physics based upon cavitational and noncavitational effects.

We truly need to temper our enthusiasm for ultrasound photos of our babies and reassess whether this tool is as safe as we think it is. As a clinical tool it is extraordinarily useful, and not unlike X-rays, it has its purposes. But it isn’t just a photograph.

As a parting gift, below is a list of some of the many uses of ultrasound in medicine, manufacturing, and research. It’s been borrowed from one of our in-press publications (Williams & Casanova, 2013). I hope it might start the cogwheels turning.

Diagnostic sonography providing structural imaging, including prenatal ultrasound; The ablation of target tissue, i.e., during neurosurgery or tumor removal, and the breakdown of calculi i.e. kidney stones or gallstones; Transcranial ultrasonic stimulation, similar to transcranial magnetic stimulation (TMS); Vasodilation, providing better visualization of the vasculature during cardiovascular procedures; Targeted drug delivery, utilizing focused ultrasound to stimulate greater tissue more permeability, e.g., the blood-brain barrier, skin, etc.; Wound healing;, e.g., bone fractures and ulcers; Bactericidal properties when synergized with antibiotics; Elastography, in which ultrasound is used to determine the elasticity of a given organ which can help discern the overall health of that organ; Transmembrane delivery of products into target cells, e.g., nonviral genes or nutrients; Acoustophoresis: the use of ultrasound on an ionic medium to create an electric charge; The purification of agricultural products; Heat transfer in liquids for production of substances such as ethanol; The purification of metals; Manipulation and characterization of particles in the bio- and physical sciences; The testing of metals, plastics, aerospace composites, wood, concrete, cement, etc. in manufacturing in order to measure thickness and locate flaws within the material.