Diagnostic ultrasound ( PDFDrive )

44 PART I Physics
The AIUM Statement on Mammalian Biological Effects in Tissues With Gas Body Contrast Agents 80
APPROVED MARCH 25, 2015
Presently available ultrasound contrast agents consist of suspensions
of gas bodies (stabilized gaseous microbubbles). The
gas bodies have the correct size for strong echogenicity with
diagnostic ultrasound and also for passage through the microcirculation.
Commercial agents undergo rigorous clinical testing
for safety and eficacy before Food and Drug Administration
approval is granted, and they have been in clinical use in the
United States since 1994. Detailed information on the composition
and use of these agents is included in the package inserts.
In the United States, contrast agents have been approved for
opaciication of the left ventricular chamber and delineation of
the left ventricular endocardial border. Outside the United States,
additional approved indications include imaging lesions of the
breast and liver, portal vein, and extracranial carotid and
peripheral arteries. Many other diagnostic applications are under
development or clinical testing.
Contrast agents carry some potential for nonthermal bioeffects
when ultrasound interacts with the gas bodies. The mechanism
for such effects is related to the physical phenomenon of
acoustic cavitation. Several published reports describe adverse
bioeffects in mammalian tissue in vivo resulting from exposure
to diagnostic ultrasound with gas body contrast agents in the
circulation. Induction of premature ventricular contractions by
triggered contrast echocardiography in humans has been
reported for a noncommercial agent and in laboratory animals
for commercial agents. Microvascular leakage, killing of cardiomyocytes,
and glomerular capillary hemorrhage, among other
bioeffects, have been reported in animal studies. Two medical
ultrasound societies have examined this potential risk of bioeffects
in diagnostic ultrasound with contrast agents and provide
extensive reviews of the topic: the World Federation for
Ultrasound in Medicine and Biology Contrast Agent Safety
Symposium 81 and the American Institute of Ultrasound in
Medicine 2005 Bioeffects Consensus Conference. 62 More
recently, the British Medical Ultrasound Society issued a detailed
assessment of methods for the safe use of diagnostic ultrasound,
including use of contrast agents. 82 Based on a review
of these reports and recent literature, the Bioeffects Committee
has issued the following statement.
STATEMENT ON MAMMALIAN BIOLOGICAL EFFECTS
OF DIAGNOSTIC ULTRASOUND WITH GAS BODY
CONTRAST AGENTS
Induction of premature ventricular contractions, microvascular
leakage with petechiae, glomerular capillary hemorrhage, local
cell killing, and other effects in mammalian tissue in vivo have
been reported and independently conirmed for diagnostic
ultrasound exposure with a mechanical index (MI) above about
0.4 and a gas body contrast agent present in the circulation.
Although the medical signiicance of such microscale bioeffects
is uncertain, minimizing the potential for such effects
represents prudent use of diagnostic ultrasound. In general,
for imaging with contrast agents at an MI above 0.4, practitioners
should use the minimal agent dose, MI, and examination time
consistent with eficacious acquisition of diagnostic information.
In addition, the echocardiogram should be monitored during
high-MI contrast cardiac-gated perfusion echocardiography,
particularly in patients with a history of myocardial infarction
or unstable cardiovascular disease. Furthermore, physicians
and sonographers should follow all guidance provided in the
package inserts of these drugs, including precautions, warnings,
and contraindications.
AIUM, American Institute of Ultrasound in Medicine.
Reproduced with permission from American Institute of Ultrasound in Medicine (AIUM). Statement on mammalian biological effects in tissues
with gas body contrast agents. Laurel, MD: AIUM; 2015. Available from: http://www.aium.org/oficialStatements/25. Approved March 25, 2015.
Cited October 7, 2016. 80
Considerations for Increasing
Acoustic Output
Situations arise where increasing acoustic output in ultrasound
imaging could provide improved performance, particularly at
signiicant depths. he desire to increase acoustic output was
the original impetus for the development of the FDA 510K Track
3 mechanism in situations in which imaging was challenging
for deep tissue structures, particularly in obstetrics. Modes such
as tissue harmonic imaging and elasticity and shear wave imaging
may also beneit from similar considerations.
A working group of the Output Standards Subcommittee of
the AIUM Technical Standards Committee examined on the
potential beneits and risks of conditionally increased acoustic
pressure. he resulting white paper 83 provides a rationale
for a three-tiered approach for conditionally increased acoustic
output that follows the model employed for elevated output in
magnetic resonance imaging, and concludes with summary
recommendations to facilitate clinical studies monitored by an
institutional review board to investigate the beneits of an
increased acoustic output in speciic tissues. One of the fundamental
assumptions in the MI calculation is the presence of a
preexisting gas body. Based on theoretical predictions and
experimentally reported cavitation thresholds for tissues that do
not contain preexisting gas bodies, the working group found
this assumption to be overly conservative and concluded that
exceeding the recommended maximum MI given in the FDA
guidance could be warranted without concern for increased risk
of cavitation in these tissues. In the future, the ultrasound research
community will need examine how much improvement in
diagnostic ultrasound imaging might be achieved with increased
acoustic output.
Mechanical Index
Calculations for cavitation prediction have yielded a trade-of
between peak rarefactional pressure and frequency. 84 his