Fleischer’s Sonography in Obstetrics & Gynecology

1425 Pages·2017·155.048 MB·English

by  Arthur C. Fleischer et al.

TRIBUTE
This book, previously entitled simply Sonography in ous awards and honors, among them are the Larry Mack
Obstetrics and Gynecology, is now entitled Fleischer’s Award for Best Research Paper by the Society of Radiologists
Sonography in Obstetrics and Gynecology, in honor of the in Ultrasound in 1998, the William Fry Award for Outstanding
lead author, Arthur C. Fleischer, MD, whose brilliance, Contributions to Ultrasound by the American Institute
intellect, and experience have spanned eight editions. of Ultrasound in Medicine in 1999, the Frank H. Boehm
Arthur C. Fleischer was born in Miami, Florida in Award for Contribution to Continuing Medical Education
1952. His parents were Lucille and Eugene. Lucille was by Vanderbilt University School of Medicine in 2005, and the
a lifelong learner and educator, graduating from Hunter Distinguished Alumnus Award from the Medical College of
College in 1942 (when she was 17), obtaining a Master’s Georgia in 2007. In 2011, Dr. Fleischer was honored with the
in Education from the University of Miami in 1951, and Cornelius Vanderbilt Chair in Radiology.
graduating first in her class at the University of Miami Art and Lynn have three children, Braden, Jared, and
School of Law in 1958. Eugene attended the University of Amy, and one grandson, Jakob. When asked about her
Miami after military service, became a general contractor father, Amy had the following words:
in Miami, and was instrumental in starting a new Reform
Jewish congregation, Temple Beth Am in Kendall, Florida.
Art Fleischer’s grandparents were Hungarian immigrants The essence of Dr. Fleischer (our dad, or “Daddio,” as we
who came to New York City from Budapest in 1921. As know him) is exemplified by an unconditional love of learn­
a child, Art was fortunate to excel at equestrian competi- ing. Whether our family discussions took place at the dinner
tions and was state champion from 11 to 18 years of age. At table or at his favorite lunch spot (let’s be honest, most of
Emory University, he completed his thesis on ultrasound our chats involved food), he always exuded an enthusiasm
enhancement of treatments and received his BS degree, for learning.
magna cum laude, in biology in 1973. He met Lynn in 1974
In fact, the most valuable gift our dad gave us (besides
through the introduction from a mutual medical school
life itself!) is his infectious curiosity. His passion for new
friend, and they were married in 1975.
technology is not only evidenced by the every­growing stack
In 1976, he received the MD degree from the Medical
of medical and academic publications he has authored
College of Georgia at Augusta, and in 1980, he complet-
(during his 40­year career) but also by the abundant sea of
ed the Radiology Residency/Fellowship at Vanderbilt
gadgets in his office! His thirst for innovative tools and tech­
University Medical Center in Nashville, Tennessee.
nology is unquenchable, even when our mom threatens to
Dr. Fleischer began his medical career in 1974 as the
purge his “toys” in order to make a path through the house.
Acting Director of Diagnostic Ultrasound at the Medical
College of Georgia. He came to Vanderbilt University School In amongst these toys, a plethora of textbooks, articles, pho­
of Medicine in 1976 and has held the following positions: tos, and old x­ray films make our home a monument to his
Acting Director of Diagnostic Ultrasound; Clinical Fellow in staggering medical career. To us, such tangible evidence—of
Ultrasound; Assistant Professor (Radiology and Obstetrics which this book is now a vital part—will always serve to
and Gynecology); and Associate Professor (Radiology and represent his most deeply held belief in the value of asking
Obstetrics and Gynecology). Additionally, Dr. Fleischer was good questions while seeking new understanding about the
Visiting Professor in Radiology (Diagnostic Ultrasound) world.
at Thomas Jefferson University Hospital. Presently, he is
Amy Fleischer, MS, OTR/L, on behalf of Art’s
Professor of Radiology and Radiological Sciences (1987);
three children
Professor of Obstetrics and Gynecology (Secondary) (1987);
Medical Director of the Sonography Training Program
Luis Gonçalves, MD, has the following observations:
(1981); and Medical Director of Ultrasound.
Dr. Fleischer has been active in several specialty There are moments in life when one wonders about how the
societies, including the American Institute of Ultrasound Universe conspires to align with perfection those people who
in Medicine (Board of Governors, Fellow), the American eventually become a permanent part of our path on Earth.
College of Radiology (Fellow), the Society of Radiologists in I would like to take this moment to acknowledge the oppor­
Ultrasound (Fellow), and the Society for the Advancement tunity of having Arthur Fleischer cross my path 24 years
of Women’s Imaging (Cofounder and President). ago at Vanderbilt University. Art has certainly inspired me
Professor Fleischer has authored more than 200 then and will continue to inspire those of us who have been
research papers regarding clinical aspects of diagnostic fortunate enough to have crossed his path and know first­
ultrasound and 23 textbooks involving the use of diagnostic hand the enormity of the human being who teaches and
sonography in obstetrics/gynecology. He has received numer- leads with a light heart.
Fleischer_FM_i-xxiv.indd 21 08/09/17 5:18 pm
Tribute xxii
Eugene C. Toy, MD, on behalf of the tens of thousands of knowledge, and so much zeal, and so much compassion
physicians, sonographers, residents and students who have can be in one person!” Dr. Fleischer has been one the cor­
been touched by Dr. Art Fleischer, has these words: nerstones in advancing imaging in women’s health over the
past 40 years, particularly in the areas of gynecologic ultra­
Art Fleischer has been a tremendous inspiration to everyone
sound. Not only has he propelled this embryologic science
around him. He has an amazing sense of humor, a consci­
into a maturing and exciting field in science and informa­
entiousness that goes far beyond the normal “call of duty,”
tion, he has also put his own personal heart and soul into
and a dedication to women’s health through imaging and
gynecologic sonography. I feel so fortunate to be able to call
the prevention and diagnosis of disease. Art is an amazing
Art Fleischer my friend, mentor, and inspiration. For the
educator, and I have sat in his conferences amazed at how
tens of thousands who use imaging to help treat women, and
much he is able to teach—from the anatomical structures,
the millions of women who are dependent on this modal­
to the imaging, to the disease. More than all of this, Art has
ity for their care, we pause a moment to give tribute to a
a tremendous love for people and cares so deeply about all
man who worked tirelessly in his significant contributions
of those who are fortunate enough to cross paths with him.
to the science and art of gynecologic sonography. For this
One physician who was in a medical school radiology rota­
reason, we have entitled this book, Fleischer’s Sonography
tion with Art summed it up: “I don’t know how so much
in Obstetrics and Gynecology.
Fleischer_FM_i-xxiv.indd 22 08/09/17 5:18 pm
PART 1
GENERAL OBSTETRIC
SONOGRAPHY
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2 Part 1 GENERAL OBSTETRIC SONOGRAPHY
Chapter 1
ULTRASOUND BIOEFFECTS AND SAFETY:
WHAT THE PRACTITIONER SHOULD KNOW
Jacques S. Abramowicz ● Eyal Sheiner
Key Terms1 7. Output Display Standard (ODS): actual name—
Standard for Real-Time Display of Thermal and
1. Acoustic streaming: movement of tissue or fluid, Mechanical Acoustic Indices on Diagnostic Ultra-
resulting from the passage of alternating positive sound Equipment. Introduced to make end users
and negative pressures of the ultrasound wave. Can aware, in real time, of the potential effects of ultra-
also result from movements of bubbles, as a result of sound in tissues. See also mechanical index and
changes in pressure. thermal index.
2. ALARA principle: stands for As Low As Reasonably 8. Radiation force: force resulting from absorption of
Achievable, a way to obtain the best, clinically rel- some of the energy of the acoustic wave by tissue
evant image while keeping ultrasound intensity and and transformation into heat.
exposure as low as possible. 9. Scanned mode: refers to the ultrasound beam
3. Cavitation: bubble activity, secondary to ultrasound moving through the field, with energy distributed
insonation. The positive aspect of the ultrasound over a large volume, such as in B-mode and color-
pressure wave causes compression of the bubble flow Doppler.
while the negative part, also called rarefactional, 10. Thermal index (TI): expresses the potential for
causes production of the bubbles or expansion of temperature increase in tissues traversed by the
existing ones. Cavitation can be stable or inertial. ultrasound wave. It is given by the ratio of the power
emitted by the transducer to the ultrasonic power
• Stable cavitation: bubble activity where bubble required to raise tissue temperature by 1°C for the
does not collapse (see inertial cavitation) but is
specific exposure conditions. This is a relative indi-
moving back and forth in the tissue or fluid, thus
cation and does not necessarily correspond to the
potentially causing the surrounding medium to
actual temperature increase. One of three thermal
flow (ie, stream, hence the term streaming).
indices is displayed, based on whether soft tissue
• Inertial (previously known as transient) cavita-
(TIS, mostly first and early second trimesters), bone
tion: bubbles that are compressed and expanded (TIB, late second and third trimesters), or adult cra-
but with each compressing (positive) component,
nium (TIC) is being scanned.
causing the volume to diminish ever more, until
11. Unscanned mode: the ultrasound beam is station-
collapse occurs. This collapse can generate tre-
ary with power concentrated along a single line,
mendously elevated temperature and pressure
such as in M-mode and spectral Doppler.
for an extremely short time and over an extremely
short space (called an adiabatic reaction). This can
result in production of several more bubbles, local
cell damage, and/or generation of free radicals. INTRODUCTION
4. Derating: action of multiplying a value measured in
“Is this safe for my baby?” Ultrasound practitioners hear
water with standard methods by a correction factor
this question almost every day in clinical practice. The
to account for the attenuation of the ultrasound field
answer generally given is: “Of course. Ultrasound is not
by the tissue traversed by the beam (usually 0.3 dB/
x-rays, it is not invasive; it has been used for close to sixty
cm/MHz).
years and is perfectly safe.” While this answer may, in fact,
5. Dwell time: the time during which the ultrasound
contain some correct facts (ultrasound is not x-rays), the
beam impinges on a specific organ, body part, or
concept of perfect safety is not scientifically valid, and
entire organism.
furthermore, the level of knowledge regarding poten-
6. Mechanical index (MI): expresses the potential for
tial effects of ultrasound in tissues is, by and large, very
nonthermal (also known as mechanical) effects in
low among end-users of this technology. Ultrasound in
tissues traversed by the ultrasound wave. Depends
obstetrics is convenient, painless, and results are available
on the pressure and the frequency (=P/ f).
immediately. The belief exists that is does not pose any risk
Fleischer_CH01_p001-p024.indd 2 08/09/17 10:50 am
Chapter 1 Ultrasound Bioeffects and Safety: What the Practitioner Should Know 3
to the pregnant patient or her fetus. Ultrasound, however, 6
is a form of energy and, as such, has effects in biological Resolution
tissues (bioeffects). The physical mechanisms responsible Penetration
for these effects are nonthermal (mechanical) or thermal. 5
The nonthermal mechanisms can further be separated
into acoustic cavitation (inertial and noninertial) and
noncavitational mechanisms, ie, acoustic radiation force
4
(time-averaged force exerted by the ultrasound beam),
acoustic radiation torque (producing in the insonated tis-
sue a tendency to rotate or spin), and acoustic streaming
(circulatory flow). It is the role of science to show whether 3
any of these bioeffects may be harmful. The question has
been debated since the introduction of ultrasound in clini-
cal obstetrics, particularly as it relates to the fetal nervous 2
system2,3 and continues to be discussed currently.4-9(1)
This chapter presents basic notions of acoustics and
physics as they relate to ultrasound, examines some
1
literature on bioeffects and the safety of ultrasound,
reviews statements of various ultrasound organizations,
and affords a practical approach to limit the potential risks
to the fetus of exposure to diagnostic ultrasound (DUS). 0
Figure 1-1.
Resolution (solid line) and penetration (dotted line) as a
BASIC PHYSICS OF ULTRASOUND function of increasing frequency, represented by the x-axis. Units on the
y-axis are not actual but representative of increasing values. The green
A detailed description of ultrasound physics can be found arrow represents the goal of improving penetration at high frequencies.
in various publications.10-12 However, certain properties of
ultrasound are very important when trying to understand (better resolution), the lower the penetration of the beam
safety and bioeffects. Equally important are tissue charac- through a given tissue (Figure 1-1).
teristics, such as attenuation coefficient. A basic knowl- Diagnostic ultrasound is pulsed, ie, pulses of acoustic
edge of instrument controls (“knobology”) is essential not energy separated by “silent” gaps. The number of pulses
only for appropriate clinical usage, but it is imperative to occurring in 1 second is the pulse repetition frequency
avoid potential harm. (PRF) and is controlled by the instrument in B-mode. In
Doppler mode, it can be altered by the end user. Another
The Ultrasound Wave important parameter is the duty factor: this is the fraction
of time that the pulsed ultrasound is on. With an increase
Sound is a mechanical vibratory form of energy. It propa- in PRF, the duty factor increases. The pulse amplitude
gates through a medium by means of the motions of reflects pressure and is the maximum variation from the
the particles in the medium, under the influence of the baseline, expressed in MPa’s. Since the ultrasound wave is
alternating positive and negative components of the wave. sinusoidal, there are periods of positive and negative pres-
Megapascal (MPa) is the unit for pressure. Ultrasound sure. When the ultrasound wave exerts pressure on the
instrumentation can generate peak pressures of 5 MPa resisting insonated tissue, work is produced. The ability of
and above. This is in comparison to the atmospheric pres- the wave to do work is its energy (in joules). The rate at
sure, which is 0.1 MPa. Several other characteristics define which the energy is transformed from one form to another
the ultrasound beam. The ultrasonic wave progresses in is the power (in watts or milliwatts). Intensity represents
the insonated tissue at a velocity that is related to the the rate at which energy passes through area unit. Average
sound characteristics as well as the tissue properties. For intensity of a beam is expressed by the beam power (in
practical purposes, the average speed of sound propaga- milliwatts, mW), divided by the cross-sectional area of the
tion in biological tissues is estimated at 1540 ms/sec. beam (in cm2) and is, therefore, expressed in mW/cm2. As
Frequency is the number of cycles per second, measured stated earlier, DUS is performed with a pulsed wave. The
in hertz (Hz). The limits of human hearing spans from intensity is proportional to the square of the instantaneous
approximately 20 to 20,000 Hz. Diagnostic ultrasound is, ultrasound wave pressure. There are pulses of energy
generally, 2 to 10 million Hz (megahertz, MHz). Wave- intermingled with periods where no energy is emitted.
length is the distance between 2 corresponding points Depending on the time and location of the measurement,
on a particular wave. It is inversely proportional to the several parameters can be described in relation to time
frequency. Equipment resolution (the shortest distance or space: temporal peak intensity (the greatest intensity),
between 2 objects or parts of an object to be represented average intensity over time, ie, including “silent” time
by 2 separate echoes) depends on the wavelength: axial between pulses (temporal-average intensity), maximal
resolution ranges between 2 and 4 wavelengths. Hence, intensity at a particular location (spatial-peak intensity),
the shorter the wavelength (ie, the higher the frequency), as well as average-spatial intensity. By combining time
the better the resolution (the distance between 2 points and space, 6 intensities can be described: spatial average–
is smaller). The trade-off is that the higher the frequency temporal average (I ), spatial average–pulse average
SATA
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4 Part 1 GENERAL OBSTETRIC SONOGRAPHY
transesophageal or, in obstetrics and gynecology, transvaginal
VALUES OF I BY MODALITY
Table 1-1 SPTA scanning. Another possibility is increasing the power of the
AND YEAR OF DEFINITION
instrument, resulting in improved resolution, as depicted by
the green arrow in Figure 1-1. This is seemingly simple, but
Modality/ 1976 1986 1992
instrument outputs are regulated in the United States (see
Application Values Values Values
The Output Display Standard section). Another important
parameter is acoustic impedance, which can be described
Fetal imaging 46 94 720
as the opposition to transmission or progression of the ultra-
Cardiac 430 430 720 sound wave. It is proportional to the velocity of sound in the
tissue (estimated at 1540 ms/sec) and to the tissue density.
Peripheral vessel 720 720 720
Ophthalmic 17 17 17 Instrument Outputs
Note: All are derated values in mW/cm2. Although some publications of various instrument outputs
Data from Nyborg WL. Biological effects of ultrasound: development of safety are available,20-22 these are generally quickly outdated, since
guidelines. Part II: general review. Ultrasound Med Biol. 2001;27:301-333;
Abramowicz JS. Prenatal exposure to ultrasound waves: is there a risk? Ultra- manufacturers introduce new commercial machines to the
sound Obstet Gynecol. 2007;29:363-367; Gressens P, Huppi PS. Are prenatal market (or modify existing ones) at a rate too fast for imme-
ultrasounds safe for the developing brain? Pediatr Res. 2007;61:265-266.
diate objective evaluation. From a clinical standpoint, there is
no easy way to verify the actual output of the instrument in
(I ), spatial average–temporal peak (I ), spatial peak– use. In addition to the variety of instruments, each attached
SAPA SATP
temporal average (I ), spatial peak–pulse average (I ), transducer will generate a specific output, further compli-
SPTA SPPA
and spatial peak–temporal peak (I ). The most practical, cated by the different modes that may be applied.23 When
SPTP
and commonly referred to, is the I . comparing modes, the I increases from B-mode (34 mW/
SPTA SPTA
The maximal permitted value varies by clinical applica- cm2, average) to M-mode to color Doppler to spectral Dop-
tion. This had been determined in 1976 by the US Food and pler (1180 mW/cm2). Average values of the temporal aver-
Drug Administration (FDA),13 but was modified in 1986.14 aged intensity are 1 W/cm2 in Doppler mode but can reach 10
The most recent definition dates from 1992.15 These values W/cm2.23 Therefore, caution should be exercised when apply-
are shown in Table 1-1. One can observe from the table that, ing Doppler mode, particularly in the first trimester. Color
for fetal imaging, the I has been allowed to increase by a Doppler, while having higher intensities than B-mode, is still
SPTA
factor of almost 16-fold from 1976 and almost 8-fold from much lower than spectral Doppler. This is mainly due to the
1986 to 1992, yet, all epidemiological information available mode of operation—sequences of pulses, scanned through
regarding fetal effects predates 1992. A remarkable fact is the region of interest (ROI or “box”). Most measurements are
that intensity for ophthalmic examination has not changed obtained from manufacturers’ manuals, having been derived
from the original 17 mW/cm2, a value approximately 42.5 in laboratory conditions. Real-life conditions may be differ-
times lower than the present allowed value for fetal scanning. ent.24 Furthermore, machine controls can alter the output. If
This will be addressed in more detail further in the chapter. one keeps in mind that, for instance, the degree of tempera-
ture elevation is proportional to the product of the amplitude
Tissue Characteristics of the sound wave by the pulse length and the PRF, it becomes
immediately evident why any change (augmentation) in these
When the ultrasound wave travels through a medium, its properties can add to the risk of elevating the temperature, a
intensity diminishes with distance.16 In completely homo- potential mechanism for bioeffects (see Thermal Effects). The
geneous, idealized materials, the signal amplitude would be 3 important parameters under end-user control are the scan-
reduced only because the wave is spreading. Biologic tissues, ning (or operating) mode, including transducer choice; the
however, are different and induce further weakening by system setup and output control; and the dwell time.
absorption and scattering (an effect called attenuation) and
by reflection. Many models have been described to help cal- 1. Scanning mode: as mentioned previously, B-mode
culate attenuation, particularly in obstetrical scanning,17 but carries the lowest risk, and spectral Doppler carries the
the most commonly used model uses an average attenuation highest (with M-mode and color Doppler in between).
of 0.3 dB/cm/MHz.18 It is important to note that the attenu- High pulse repetition frequencies are used in pulsed
ation increases logarithmically with frequency and distance Doppler techniques, generating greater temporal aver-
traveled. Technically, many measurements of acoustic power age intensities and powers than B- or M-mode, and
are performed in water, which has almost no attenuation. hence greater heating potential. An additional risk is
To apply these calculations to tissues, values are multiplied that since, in spectral Doppler, the beam needs to be
by this factor, an action called derating.19 Absorption is the held in relatively constant position over the vessel of
sound energy being converted to other forms of energy, and interest, there may be a further increase in temporal
scattering is the sound being reflected in directions other average intensity. Naturally, transducer choice is of
than its original direction of propagation. Since attenua- great consequence since it will determine frequency,
tion is proportional to the square of sound frequency, it penetration, resolution, and field of view.
becomes evident why higher frequency transducers have less 2. System setup: starting or default output power and,
penetration (but better resolution; see Figure 1-1). One needs, particularly, mode (B-mode, Doppler, etc) control
therefore, to be closer to the organ of interest, such as through changes. A subtler element is fine tuning performed
Fleischer_CH01_p001-p024.indd 4 08/09/17 10:50 am
Chapter 1 Ultrasound Bioeffects and Safety: What the Practitioner Should Know 5
by the examiner to optimize the image and influence
output but with no visible effect (except if one follows
thermal index [TI] and/or mechanical index [MI] dis-
plays). Controls that regularize output include focal
depth (usually with greatest power at deeper focus but
occasionally, on some machines, with highest power
in the near field); increasing frame rate; and limit-
ing the field of view, for instance, by high-resolution
magnification or certain zooms (Figure 1-2).
3. In Doppler mode, changing sample volume and/or
velocity range (all done to optimize received signals)
changes output. Video Clip 1 demonstrates change in
output (as observable by change in TI) when changing
the focal distance. A very important control in every
mode is receiver gain. It often has similar effects to
the above controls on the recorded image but none
on the output of the outgoing beam, and is therefore
A
completely safe to manipulate (Figure 1-3). In other
words, the receiver gain should be maximized before
output is increased. In addition, over the years, output
of instruments has increased.22, 25
B
A
C
Figure 1-3.
A: Image obtained with 100% power (blue arrow). Note
MI = 1.2 and TI + 0.1 (yellow arrow). B: Power has been reduced to 85%
B
(blue arrow). Note MI = 0.7 and TI + 0.0 (yellow arrow). This image is less
Figure 1-2. diagnostic. C: Receiver gain has been increased. Power is unchanged from
Acoustic output changes (as reflected by changes in TI).
B (nor are MI and TI) but image is as diagnostic as A.
A: Nonzoomed image. Please note TI = 0.2. B: Zoomed image. Please
note TI = 1.0 (arrow).
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6 Part 1 GENERAL OBSTETRIC SONOGRAPHY
4. Dwell time: is directly under the control of the exam- The organ at greatest risk is the central nervous
iner. Interestingly, dwell time is not taken into account system (CNS) due to a lack of compensatory growth of
in the calculation of the safety indices (thermal index, damaged neuroblasts. In experimental animals the most
TI and mechanical index, MI,) nor, in general, until common defects are of the neural tube, microphthalmia,
now, reported in clinical or experimental studies. cataract, and microencephaly, with associated functional
However, one needs to remember that it takes only and behavioral problems.32 Defects of craniofacial develop-
one pulse to induce cavitation, and about a minute ment including clefts,36 the axial and appendicular skeleton,37
to raise temperature to its peak. Directly related with the body wall, teeth, and heart38 are also commonly found.
dwell time is examiner experience: knowledge of Hyperthermia in utero (due to maternal influenza) has
anatomy, bioeffects, instrument controls, and scanning been described as a risk factor for congenital anomalies39,40
techniques. It can be safely assumed that the more and subsequent childhood psychological/behavioral distur-
experienced the examiner, the less scanning time will bances41 and, more particularly, schizophrenia.42 Nearly all
be needed to obtain the needed diagnostic images. these defects have been found in human epidemiological
studies following maternal fever or hyperthermia during
A standardized method of providing the end user pregnancy. It should be emphasized that these investigations
a parameter related to acoustic output and expressing have not involved ultrasound-induced hyperthermia effects.
potential for bioeffects is clearly needed; hence, the gener- Yet, there are data on the effects of hyperthermia and mea-
ation of the Output Display Standard, based on the 2 most surements of in vivo temperature induced by pulsed ultra-
likely interactions of ultrasound with tissues: thermal sound, but not in human beings.43-46 These data have been
and nonthermal or mechanical.26 widely reviewed.32,35,47-49 There is, however, a serious lack of
data that examine the effects of ultrasound while rigorously
THERMAL EFFECTS excluding other confounding factors. Two widely accepted
facts are that ultrasound has the potential to elevate the
Normal core human body temperature is generally accepted temperature of the tissues being scanned,50-53 and elevated
to be 37°C (98.6°F) with a diurnal variation of ±0.5°C to 1.0°C, maternal temperature, whether from illness or exposure to
although 36.8°C ± 0.4°C (95% confidence interval) may be heat, can produce teratologic effects.31,32,35,54-56 The major
closer to the actual mean for large populations.27 During question is, therefore, whether DUS can induce a harmful
the entire gestation, temperature of the human embryo/ rise in temperature in the fetus.57-59 Some believe that this
fetus is higher than maternal core body temperature28 and temperature rise is, in fact, a major mechanism for ultrasound
gradually rises until the final trimester (near term). The fetal bioeffects.30,35 Temperature elevation in the insonated tissue
temperature generally exceeds that of the mother by 0.5°C.29 can be calculated and estimated fairly accurately if the field is
Thermally induced teratogenesis (production of congenital sufficiently well characterized.60,61 For prolonged exposures,
malformations in an embryo or fetus) has been demon- temperature elevations of up to 5°C have been obtained.57
strated in many animal studies, as well as several controlled Temperature change in insonated tissues depends on the
human studies.30 While elevated maternal temperature in balance between heat production and heat loss. A particular
early gestation has been associated with an increased inci- tissue property that strongly influences the amount of heat
dence of congenital anomalies,31 the majority of these studies transported is local perfusion, which very clearly diminishes
do not involve ultrasound-induced temperature elevation. the risk, if present. Similar experimental conditions caused
Edwards and others have demonstrated that hyperther- a 30% to 40% lower maximal temperature increase in live
mia is teratogenic for numerous animal species, including versus dead sheep fetuses exposed in the near field,45 while
humans,32 and suggested a 1.5°C temperature elevation in guinea pig fetuses exposed at the focus the difference was
above the normal value as a universal threshold.33 Some approximately 10%.46 These findings were estimated to be
scientists believe that there are, indeed, temperature thresh- secondary to vascular perfusion in live animals. A significant
olds for hyperthermia-induced birth defects, hence the As cooling effect of vascular perfusion was observed only when
Low As Reasonably Achievable (ALARA) principle. There the guinea pig fetuses reached the stage of late gestation near
is, however, some evidence that any positive tempera- term, when the cerebral vessels were well developed. In the
ture differential for any period of time has some effect. In midterm, there was no significant difference when guinea
other words, that there may be no thermal threshold for pig fetal brains were exposed, alive (perfused) or postmortem
hyperthermia-induced birth defects.34 From careful thermal (nonperfused), in the focal region of the ultrasound beam.46
dose determinations, derived from published literature in In early pregnancy, under 6 weeks gestation, there
this area, it may be that hyperthermia-induced birth defects appears to be minimal maternal-fetal circulation, that is,
are produced in accordance with an Arrhenius relation for minimal fetal perfusion, which may potentially reduce heat
chemical rate effects, and thus have no threshold.35 Any tem- dispersion.62 The lack of perfusion is one reason why the
perature increment for any period of time has some effect. spatial peak-temporal average intensity (I ) for ophthal-
SPTA
Likewise, the higher the temperature differential or the lon- mic applications has been kept very low, in fact much lower
ger the temperature increment, the greater the likelihood of than peripheral, vascular, cardiovascular, and even obstetric
producing an effect. Gestational age is a vital factor: milder scanning, despite the general increase in acoustic power
exposure during the preimplantation period can have similar that was allowed after 1992 (see Table 1-1). There are some
consequences to more severe exposures during embryonic similarities in physical characteristics between the early,
and fetal development and can result in prenatal death and first-trimester embryo and the eye. Neither is perfused; they
abortion or a wide range of structural and functional defects. can be of similar size; and protein is present (in an increasing
Fleischer_CH01_p001-p024.indd 6 08/09/17 10:50 am
Chapter 1 Ultrasound Bioeffects and Safety: What the Practitioner Should Know 7
elevation is proportional to the product of the wave ampli-
tude, length of the pulse, and PRF. Hence, manipulating any
of these via instrument controls will alter the in situ condi-
tions. It is clear that temperature increases of 1°C are easily
reached in routine scanning.67 Elevation of up to 1.5°C were
obtained in the first trimester and up to 4°C in the second
and third trimesters, particularly with the use of pulsed Dop-
pler.68 There is a large body of literature on heat shock pro-
teins (HSPs), the production of which is triggered by a core
temperature increase and the function of which is to protect
against hazardous effects of elevated temperature as well as
to induce some thermotolerance, ie, the ability to withstand
higher elevations than in the past, with no harmful results.69
While their production is activated by whole-body tempera-
ture elevation, and may be speculated in ultrasound-induced
thermal effects, it has not been shown to actually occur dur-
ing experimental (or clinical) insonation.
Figure 1-4.
First trimester (11 weeks) measurement of the crown-
rump length: the entire fetus is within the ultrasound beam (“whole body
MECHANICAL EFFECTS
scanning”).
Ultrasound bioeffects also occur through mechanical mech-
proportion in the fetus). As mentioned previously, one must
anisms.70,71 These are interactions between the ultrasound
then wonder why, from the time intensities were checked
wave and the tissue that do not cause a significant degree
and recommended in clinical practice, I was from the
SPTA of temperature increase (less than 1°C above physiologic
beginning and has continued to be maintained at 17 mW/
cm2, while for fetal imaging it was allowed to reach 720 temperature). These include acoustic cavitation as well as
mW/cm2, up from 46 mW/cm2. At about weeks 4 to 5, the radiation torque and force, and acoustic streaming second-
ary to propagation of the ultrasound waves. While included
gestational sac is about the size of the eye (2.5 cm in diam-
in this category, some effects are, in fact, the result of the
eter), and by week 8 it is around 8 cm in diameter. This may
mechanical interaction but are actually physical (shock
allow whole-body fetal scanning (and possibly temperature
wave) or chemical (release of free radicals) effects. Table 1-29
increase), a concept that is generally ignored in the literature
summarizes nonthermal effects described in the literature
dealing with thermal effects of ultrasound (Figure 1-4).
in laboratory or animal experiments—and not in humans—
The issue of transducer heating, which may be par-
which may be pertinent to fetal ultrasound.
ticularly relevant in the first trimester, specifically if per-
forming endovaginal scanning, is also often ignored.63,64 Investigations with laboratory animals clearly indicate
that nonthermal interactions of ultrasound fields with tis-
There are additional concerns in early gestation because
sues can produce biological effects in vivo.71 It is interesting
of minimal or lack of perfusion. Only at about weeks
10 to 11 does the embryonic circulation actually linkup
with the maternal circulation.65 There may thus be some MAJOR NONTHERMAL EFFECTS
underestimation of the actual DUS-induced temperature OF ULTRASOUND OBSERVED
in early gestation, mainly because of the absence of perfu- IN THE LABORATORY AND
Table 1-2
sion. The perfusion issue is in addition to modifications IN ANIMALS AND WITH THE
of tissue temperature due to ambient maternal and fetal POTENTIAL TO AFFECT THE
temperatures. Furthermore, motions (even very small) FETUS
of the examiner’s hand as well as the patient’s breathing
and body movements (in the case of obstetric ultrasound, Free-radical generation
both the mother and the fetus) tend to spread through Increase in cell membrane permeability
the region being heated. However, for spectral (pulsed) Erythrocyte agglutination
Growth restriction (transient decrease)
Doppler studies, it is necessary to have the transducer as
DNA single-strand break
steady as possible. This is because, in general, blood ves-
Increased sister chromatid exchange
sels are small in comparison to the general organ or body
Increased mutation frequency
size being scanned with B-mode imaging, and hand move-
Capillary petechiae
ments while performing Doppler studies will have more Vasoconstriction
undesired effects on the resulting image. As described Lung microvascular hemorrhage
earlier, the intensity (I ) and acoustic power associated Intestine microvascular hemorrhage
SPTA
with Doppler ultrasound are the highest of all the general- Neuronal migration delay
use categories. Ziskin66 reported that among 15,973 Dop- Auditory tract stimulation
pler ultrasound examinations, the average duration was 27 Tactile radiation pressure perception effect
Cardiac, premature contractions
minutes (and the longest 4 hours!).
There is a mathematical/physical relation between tem-
Modified with permission from Stratmeyer ME, Greenleaf JF, Dalecki D, et al.
perature elevation and several beam characteristics. The Fetal ultrasound: mechanical effects. J Ultrasound Med. 2008 Apr;27(4):597-605.
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