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
(c) 2007-2011 John Elder Robison