More thoughts on ultrasound, questions about risk, and autism

Last week's essay on ultrasound generated a great deal of commentary.  Some of the questions raised by readers were beyond my expertise, so I turned to Dr. Manny Casanova from the University of Louisville. He and his colleague Emily williams have spent a good bit of time studying ultrasound and its effects on cells.  They were kind enough to write the following essay and will respond to your questions here on the blog:

One problem of which we've become poignantly aware is that ultrasound, especially since the early 1990s, has been deregulated and is nowadays used to excess. Ultimately we would like to see more research into its safety, as well as tighter regulations on its use so that its risks don't outweigh the benefits. We'd also like to clarify that we're not proposing that ultrasound is "the" cause of autism. What we're proposing instead is that ultrasound may be one of many risk factors for those who have a selective vulnerability.

Many people when they first hear about ultrasound as a possible risk factor in the development of autism think it sounds like pseudoscience. Who can blame them? We've been subjected to many different hypotheses about what may be causing autism.  It seems like everyone is ultimately seeking the "holy grail" of causation. So we're all skeptical when we hear something new, especially something which seems to contradict our understanding of how we view the world-- or in this case, how we perceive the safety of ultrasound. After all, ultrasound is just a picture, right?

That's what we in our laboratory used to think until we began studying what mediates the effects of ultrasound. In the following paragraphs we hope to offer a simple explanation on the rather complex effect of ultrasound on the living cell.

Ultrasound refers to sound that has a frequency above that which can be detected by the human ear. Sound itself is the force of pressure through a solid, liquid, or gas; it causes the movement of those particles. In the case of prenatal ultrasound, the ultrasound transducer emits sonic waves into the abdomen, the sound enters the body including that of the developing embryo/fetus, bounces off the tissue, reflecting back, and that echo is measured by the transducer to form a representative visual image.

Ultrasound is currently used in a variety of ways in medicine and research, and some of these include:

1) the production of lesions in neurosurgery, similar to the use of laser;

2) transcranial (across the skull) stimulation of brain activity, similar to transcranial magnetic stimulation (TMS) or the use of electrodes;

3) vasodilation, or the widening of blood vessels, which helps in both visualization of the vasculature as well as the delivery of important medications to tissue;

4) transdermal (across the skin) delivery of medications which would normally be unable to cross the skin barrier;

5) wound healing, such as on certain bone fractures and ulcers;

6) the purification of foods via its oxidative potential;

7) the purification of metals also due to its oxidative capacity;

8) transmembrane delivery of nonviral genes into target cells (mainly used in research).

These are just a few examples of how science and medicine apply ultrasound. As you can probably guess by now, given its capacity at different levels of intensity to promote cell growth, cell destruction, alter membrane fluidity (e.g., poke temporary holes in cell membranes), and alter a cell's activity such as causing a neuron to fire, ultrasound has an incredible range of effects. It turns out it's not just a picture after all.

The physical effects of ultrasound include both its pressure on the water within and surrounding a given cell, and through the creation, oscillation (spinning), and implosion of bubbles in that same liquid. The latter is referred to as "cavitation" or the creation of a gaseous cavity within the liquid. Cavitation and noncavitational effects together can poke transient holes in cells, activate certain molecular pathways within those cells, cause temperature increases when the bubble violently implodes, promote the creation of free radicals (oxidation) when that gas escapes into the surrounding medium which can subsequently damage or even kill a cell, can cause general disarray within the cell, and at certain intensities may even promote mutations of DNA.

Most of the deadly effects on cells are generally not seen at diagnostic intensities levels. However, there is still the potential that ultrasound is altering how these cells develop and behave; i.e., it doesn't kill them, it changes them. In the case of autism, we frequently find abnormalities in neuron number and growth patterns in the brain. Given that ultrasound has the capacity to promote cellular growth, as well as its overuse in obstetrics and the apparent rising numbers of autism diagnoses, this is a prime area for scientific study. Needless to say, this is a gross simplification of our hypothesis, so for anyone interested in more detailed accounts, please contact us for further materials and we'd be glad to supply them (see minicolumn.org/people/Casanova).

Back in the 1960s, '70s, and '80s, the scientific community was very cautious about using prenatal ultrasound. As much as science knew in the day, they expressed due concern and performed a good number of safety studies. From these studies, they decided that ultrasound was ultimately safe to use in obstetrics. However, science is ever-changing and continually learning more about development. Back in the 1970s, the height of concern over ultrasound was whether it promoted spontaneous abortion or reduced postnatal survival rates, whether it promoted macroscopic growth abnormalities like differences in birth weight and overall size, and whether it caused genetic mutations. Nowadays, we know much more about the molecular biology of the cell, and more as to how development can be affected in microscopic ways which can have very big effects on behavior. Let's face it: when a postmortem examination is performed on an autistic person's brain, usually one of the most striking things about it from a macroscopic level is that there isn't anything unusual. So the differences in an autistic person's brain are indeed very subtle; they need to be teased out with various technologies, with a knowledge of the complexity of anatomical, cellular, and molecular biology, and a nuanced understanding of early development. Our science has continued to mature, but unfortunately the early safety studies on ultrasound were never updated to include this new understanding.

It's time we go back and reassess, with new knowledge, techniques, and technology, whether or not ultrasound is truly as safe as we assume it is. It's also time that the regulations on ultrasound be refined so that we can be doubly sure we're not putting our unborn infants at risk, be it for autism or some other condition.

Again, what we want to stress is that we're not advocating the disuse of ultrasound. It's an extremely vital and useful tool in medicine. But we are advocating that it be used more wisely. For those who are pregnant, we recommend that ultrasound should not be performed during the first trimester unless it is an at-risk pregnancy, and especially not within the first 8 weeks of gestation. The first 8 weeks is the period when the greatest intensity of growth occurs-- and therefore when the greatest damage can be done. Be cautious of early and unnecessary ultrasounds. In addition, don't use fetal heart rate monitors for private use because these are handheld ultrasounds.

                                                                                                            Manuel F. Casanova, M.D.

                                                                                                            Emily L. Williams