Contrast-Enhanced Ultrasound Imaging
Thomas R. Porter
Joan J. Olson
Feng Xie
1. The current Food and Drug Administration (FDA) indication for ultrasound contrast is:
A. Myocardial perfusion.
B. Doppler enhancement.
C. Stress echocardiography.
D. Improvement in left ventricular opacification.
View Answer
1. Answer: D. Although contrast has been shown to improve reader confidence during stress echocardiography, and to provide myocardial perfusion data that adds incremental value, the current FDA approval is only to improve left ventricular opacification. It is not approved for stress echocardiography or for a myocardial perfusion indication.
2. What specific change in ultrasound contrast agent composition led to improved transpulmonary passage and left ventricular opacification for the current FDA-approved agents?
A. Change in microbubble shell composition.
B. Change in gas molecular weight.
C. Utilization of nitrogen gas-filled microbubbles.
D. Continuous infusion of contrast instead of bolus injection.
View Answer
2. Answer: B. The change from room air gas to higher-molecular-weight gases has led to longer persistence of microbubbles (due to reduced diffusivity and solubility) and consistent left ventricular opacification following venous injection or infusion. Although newer microbubbles contain polymer shells that may produce consistent left ventricular opacification following venous injection, they are not yet approved.
Table 11-1. Commercially Available Very Low MI Pulse Sequence Schemes and their Mechanism of Action | ||||||||||||||||||||||||||||||
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3. The very low mechanical index (MI) imaging techniques available on most systems have been shown to permit which of the following off- and on-label clinical applications?
A. Myocardial perfusion imaging.
B. Endocardial border resolution.
C. Detection and evaluation of intracardiac masses.
D. All of the above.
View Answer
3. Answer: D. Very low MI imaging techniques are available on most commercially available systems (Table 11-1). These permit the enhancement of microbubble nonlinear behavior at these very low MIs, while simultaneously reducing background tissue signals (which do not exhibit nonlinear behavior at very low MIs). This has been utilized not only to provide improved endocardial border delineation, but also to detect myocardial perfusion and perfusion of intracardiac masses.
4. The utilization of ultrasound contrast for evaluation of regional and global left ventricular systolic function, when compared to two-dimensional imaging alone, has demonstrated all of the following except:
A. Better correlation with magnetic resonance imaging ejection fraction measurements.
B. Reduced interobserver variability.
C. Improved assessment of myocardial viability.
D. Improved regional wall motion analysis.
View Answer
4. Answer: C. Multicenter investigations using low MI (0.3 or less) contrast specific imaging with ultrasound contrast have demonstrated closer agreement with magnetic resonance imaging measurements of both regional wall motion and ejection fraction. These studies were resting studies not analyzing myocardial perfusion imaging pulse sequence schemes and thus could not assess myocardial viability.
5. Power modulation involves which of the following physical principles?
A. Alternating pulse amplitude.
B. Alternating pulse phase polarity.
C. Alternating both pulse phase and amplitude.
D. Alternating fundamental and harmonic signals.
View Answer
5. Answer: A. Refer to Table 11-1. Contrast pulse sequencing involves the very low MI imaging method of alternating polarity and amplitude, while pulse inversion Doppler is transmitting pulses of alternating polarity. Power modulation involves transmitting pulses of alternating amplitude. All of these techniques, when used at MI settings <0.2, produce myocardial and left ventricular cavity contrast during microbubble infusions or injections, because microbubbles exhibit nonlinear responses (distortions of the sound wave in both the fundamental and harmonic frequencies) at this MI while myocardium and valves do not. Imaging transducers are capable of detecting only these nonlinear responses (fundamental and harmonics) while cancelling out any linear responses. At higher MIs, tissue begins to elicit nonlinear responses, while microbubbles start to exhibit other nonlinear responses such as subharmonics, ultraharmonics, and noise (due to inertial cavitation).
6. Recent multicenter clinical trials comparing myocardial perfusion imaging with myocardial contrast echocardiography versus radionuclide imaging have been unable to demonstrate which of the following findings?
A. Improved sensitivity of myocardial contrast echo over radionuclide imaging to detect angiographic coronary artery disease (CAD).
B. Reduced specificity of myocardial contrast echo over radionuclide imaging to detect angiographically significant CAD.
C. Improved sensitivity of myocardial contrast echo over radionuclide imaging to detect singlevessel angiographic disease.
D. Improved accuracy of myocardial contrast echo over radionuclide imaging to detect angiographically significant CAD.
View Answer
6. Answer: D. The recent multicenter European study comparing real-time myocardial contrast echocardiography (RTMCE) with radionuclide SPECT during dipyridamole stress testing found that RTMCE had higher sensitivity but lower specificity for the detection of angiographically significant coronary artery disease (SPECT). This translated into no differences in test accuracy between the two perfusion imaging techniques.
7. Myocardial perfusion imaging with contrast echocardiography using real-time techniques has not been shown clinically useful in predicting the outcomes of patients in which of the following clinical scenarios?
A. Dobutamine stress echocardiography.
B. Dipyridamole stress echocardiography.
C. Emergency room chest pain evaluation.
D. Post-myocardial infarction echocardiography.
E. Stress cardiomyopathy.
View Answer
7. Answer: E. Myocardial contrast echocardiography has provided perfusion imaging information that has added incremental value over wall motion and clinical variables during stress echocardiography, in the evaluation of chest pain with a nondiagnostic EKG in the emergency department, and in the post-myocardial infarction setting. Although contrast improves the delineation of the apex and detects myocardial perfusion in patients with stress cardiomyopathy, there are no prognostic data published on its value.
8. Based on expert consensus, what is the definition of inadequate endocardial border resolution?
A. Failure to detect wall motion in five or greater segments in a 17-segment border.
B. Failure to detect two contiguous segments.
C. Failure to detect three or more contiguous segments.
D. Failure to delineate right or left ventricular endocardial segments.
View Answer
8. Answer: B. Although arbitrary, the definition of inadequate border resolution has been defined as inability to delineate two contiguous borders on a noncontrast echocardiogram.
9. Based on the most recent FDA labeling, what is still considered a contraindication to the use of all contrast agents other than Optison?
A. Allergy to blood products.
B. Inability to give informed consent.
C. Right to left intracardiac shunting.
D. Severe pulmonary hypertension.
View Answer
9. Answer: C. Since the original Box Warning in 2007, the FDA has removed several contraindications and requirements for monitoring after the administration of contrast. Although allergy to blood products is a contraindication to giving Optison, it does not pertain to all contrast agents. Severe pulmonary hypertension is no longer a contraindication. Right to left shunting remains a contraindication, but general consensus is that it does not pertain to patent foramen ovale, where contrast administration has been shown to be safe.
10. One of the impediments to using ultrasound contrast has been obtaining intravenous (IV) access. Which statement is true regarding qualifications for starting an IV line?
A. It should be performed only by certified phlebotomy technicians.
B. It requires a nurse in all US hospitals.
C. It is not routinely required for other imaging techniques such as radionuclide or magnetic resonance imaging.
D. It can be performed by sonographers.
View Answer
10. Answer: D. The most recent sonographer guidelines for contrast administration review several hospitals’ standard operating procedures for contrast administration, and in these hospitals sonographers are permitted to start IV lines. In fact, these protocols often include sonographers in both the starting of the IV line and administration of contrast. Although contrast use is severely underutilized, it is probably required for endocardial border delineation in about 30% of all echocardiograms performed. This is in comparison to radionuclide imaging and CT imaging, where IV lines are routinely required for contrast or tracer administration.
11. Which of the following is not an advantage of a continuous infusion of ultrasound contrast when compared to a bolus injection?
A. Improved left ventricular opacification.
B. Reduced left ventricular cavity acoustic shadowing.
C. It allows quantification of myocardial perfusion.
D. Reduced far-field attenuation.
View Answer
11. Answer: A. Continuous infusions of ultrasound contrast agents permit quantification of myocardial perfusion using destruction replenishment curves. Since the concentration of contrast is constant, the 1-exponential function can be utilized to examine contrast replenishment following destructive impulses. This cannot be done following a bolus injection, because of the varying contrast concentration. The bolus of contrast also can produce temporary acoustic shadowing and far-field attenuation that is seen to a lesser degree with continuous infusions.
12. Studies examining the risk versus benefit of ultrasound contrast in acute critical care settings have demonstrated:
A. Using IV ultrasound contrast is associated with a slight increase in all-cause early mortality.
B. An increased risk for anaphylactic reactions when compared to an outpatient setting.
C. A significant reduction in all-cause mortality when contrast is utilized.
D. Less beneficial effects but no difference in risk when compared to an outpatient setting.
View Answer
12. Answer: C. Large propensity-matched clinical outcomes data from the Premier database have demonstrated that patients receiving contrast-enhanced echocardiograms have an actual reduction in mortality rate when compared with patients receiving noncontrast echocardiograms.
13. In which of the following clinical settings has ultrasound transpulmonary contrast not been shown to be beneficial?
A. Detection of endovascular leaks following aortic endograft placement.
B. Detection of patent ductus arteriosus in children and adults.
C. Detection of left atrial appendage thrombi during transesophageal echocardiography.
D. Detection of intracarotid artery plaque and plaque vascularity.
View Answer
13. Answer: B. Intravenous contrast has provided additional information aside from left ventricular opacification by improving both the detection of carotid plaque and plaque neovascularity in carotid ultrasound imaging. It also has been utilized to differentiate spontaneous contrast from thrombus during transesophageal echocardiography and detect endoleaks following percutaneous vascular stent endografts. It is not utilized for detection of intracardiac shunts, which may require saline but not transpulmonary contrast agents.
14. You are giving an ultrasound contrast agent (Definity) to a patient and she experiences back pain. Which of the following statements is false?
A. You could switch to Optison if she needs additional contrast.
B. This is considered a precursor to a severe anaphylactic reaction.
C. This is most likely related to the lipid shell of the microbubble.
D. The back pain usually resolves with discontinuation of the contrast agent use.
View Answer
14. Answer: B. Back pain is an infrequent complication that has been exclusively seen with intravenous Definity use. It has not been reported with Optison, and thus this could be utilized in a patient who experiences back pain with Definity. Although the exact cause for back pain is unknown, it is most likely related to the lipid shell composition since it is not seen with albumin-shelled agents. It should not be considered a precursor to the more severe anaphylactoid reactions, which are rare (<1:10,000).
15. Which of the following conclusions have not been demonstrated with clinical and experimental trials examining the use of myocardial perfusion imaging with ultrasound contrast during dobutamine stress echo?
A. Reduced specificity compared to wall motion analysis alone in the detection of coronary artery disease (CAD).
B. Improved sensitivity for the detection of CAD compared to wall motion analysis.
C. Earlier onset of perfusion defects during demand stress when compared to wall motion.
View Answer
15. Answer: D. During demand ischemia induced with incremental dobutamine infusions, perfusion imaging with intravenous microbubbles has detected abnormalities prior to the onset of wall motion abnormalities. In single-center clinical trials, this has resulted in improved sensitivity of dobutamine stress echocardiography over wall motion analysis alone for detection of coronary artery disease. Although specificity has been reduced, overall accuracy for disease detection was still significantly higher with perfusion imaging compared to wall motion analysis. Disease detection occurs at a lower dobutamine infusion rate with perfusion imaging; however, no one has shown that this reduces the side effects or complications related to dobutamine stress echocardiography (e.g., atrial fibrillation, chest pain, ventricular arrhythmias).
16. The baseline apical 3-chamber view at end diastole and end systole was obtained on a patient (Fig. 11-1, left panels). Because of inadequate border resolution, contrast enhanced views were obtained (Fig. 11-1, right panels). What segments can be visualized with confidence on the contrast-enhanced image?
A. Apical and inferolateral (basal, mid, and distal).
B. Basal to mid anterior segments.
C. Just the anteroseptal segments.
D. Basal, mid, and distal inferior segments.
View Answer
16. Answer: A. The utilization of ultrasound contrast has been shown to improve visualization of endocardial borders of all 17 segments, although one has to ensure that attenuation of basal segments does not occur with acoustic shadowing. In this particular case, we are examining the apical 3-chamber view and thus only inferolateral, apical, and anteroseptal segments are visualized. Contrast should be utilized whenever two contiguous segments cannot be visualized on a noncontrast echocardiogram.
17. Figure 11-2 was obtained during an outpatient echocardiographic examination for atrial fibrillation and chest pain. Noncontrast images are shown in Figure 11-2A, B-mode low MI images are shown in Figure 11-2B, and very low MI power modulation images are shown in Figure 11-2C. Which of the following statements is not true regarding the contrast-enhanced images?
A. There is inadequate delineation of the apical border on the noncontrast harmonic images.
B. There is minimal myocardial tissue signal on the very low MI contrast-enhanced images.
C. A TEE may be required to better visualize the apical segments.
D. There is improved contrast signal to noise with the very low MI power modulation image.
View Answer
17. Answer: C. The very low MI image has increased contrast signal when compared with the low MI image and clearly allows visualization of the apex, which was incompletely visualized on the noncontrast study. Transesophageal echocardiography has difficulty seeing apical images due to far-field attenuation and foreshortening of apical windows. Very low MI imaging induces virtually no signal from myocardial tissue since it is only detecting nonlinear signals, which exclusively occur from microbubbles when imaging at a very low MI.
18. Figure 11-3 was obtained from a study that examined patients with pulmonary hypertension of varying degrees (Right ventricular systolic pressure or RVSP >35, RVSP >50, and RVSP >60 mm Hg) who received either IV Optison or Definity for a clinically approved indication. Which of the
following are true regarding the use of ultrasound contrast in pulmonary hypertension in this study?
following are true regarding the use of ultrasound contrast in pulmonary hypertension in this study?
A. There is increased risk only in the severe pulmonary hypertension patients (>60 mm Hg).
B. In all subsets, contrast appears to be associated with increased risk.
C. There is no additional risk with contrast in all stages of pulmonary hypertension.
D. Patients with primary pulmonary hypertension may be at increased risk over patients with secondary hypertension.
 Figure 11-2A |
 Figure 11-2B |
 Figure 11-2C |
 Figure 11-3 |
 Figure 11-4A |
 Figure 11-4B |
 Figure 11-4C |
View Answer
18. Answer: C. The study by Abdelmoneim examined whether the use of intravenous Definity or Optison contrast affected patient survival with various degrees of pulmonary hypertension (primary or secondary). As can be seen by the P values in each of the graphs, there was no significant effect of contrast use on survival. These studies, as well as others, provided sufficient data for the FDA to remove pulmonary hypertension as a contraindication to ultrasound contrast use.
19. A bolus injection of intravenous contrast was administered in the apical 4-chamber view in Figure 11-4, while imaging with a very low mechanical index (MI) pulse sequence scheme when contrast just arrives in the right ventricle (A), left ventricular cavity (B), and myocardium (C). What is true about images A, B, and C?
A. The MI is set to 0.4-0.5.
B. The MI used is creating some background tissue signals.
C. We are detecting primarily nonlinear behavior from microbubbles.
D. The middle panel delineates a resting perfusion defect.
View Answer
19. Answer: C. The very low MI imaging techniques (<0.2 MI) are designed to detect only nonlinear activity (distortions in the sound wave as it passes through a given medium) from microbubbles. The images shown do not demonstrate any signal from the myocardium or valves, which begin to elicit these same nonlinear responses at MI values of 0.3-0.4, and thus these images are obtained at much lower MI values (typically <0.2). Between 0.2 and 0.3 MI, the myocardium may already in some patients elicit this nonlinear response. In the example shown at <0.2 MI, the left ventricular microbubble cavity contrast is followed by myocardial opacification that is uniform; any isolated decrease in myocardial contrast enhancement in a basal segment (as is seen in the basal septal segment in panel C) should be interpreted with caution as these segments may exhibit attenuation with these very low MI imaging techniques.
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