Contrast Ultrasound; More Pros than Cons, of course

Contrast Enhanced Ultrasound (CEUS) is the application of ultrasound contrast medium to traditional medical sonography. Ultrasound contrast agents rely on the different ways in which sound waves are reflected from interfaces between substances. This may be the surface of a small air bubble or a more complex structure.

Commercially available contrast media are gas-filled microbubbles that are administered intravenously to the systemic circulation.

Microbubbles have a high degree of echogenicity (the ability of an object to reflect ultrasound waves). There is a great difference in echogenicity between the gas in the microbubbles and the soft tissue surroundings of the body.

Thus, ultrasonic imaging using microbubble contrast agents enhances the ultrasound backscatter, (reflection) of the ultrasound waves, to produce a sonogram with increased contrast due to the high echogenicity difference.

Contrast-enhanced ultrasound can be used to image blood perfusion in organs, measure blood flow rate in the heart and other organs, and for other applications.

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Targeting ligands that bind to receptors characteristic of intravascular diseases can be conjugated to microbubbles, enabling the microbubble complex to accumulate selectively in areas of interest, such as diseased or abnormal tissues.

This form of molecular imaging, known as targeted contrast-enhanced ultrasound, will only generate a strong ultrasound signal if targeted microbubbles bind in the area of interest.

Targeted contrast-enhanced ultrasound may have many applications in both medical diagnostics and medical therapeutics. However, the targeted technique has not yet been approved by the FDA for clinical use in the United States.

Contrast-enhanced ultrasound is regarded as safe in adults, comparable to the safety of MRI contrast agents, and better than radiocontrast agents used in contrast CT scans. The more limited safety data in children suggests that such use is as safe as in the adult population.[2]

Contrast-enhanced ultrasound is regarded as safe in adults, comparable to the safety of MRI contrast agents, and better than radiocontrast agents used in contrast CT scans.

Source: Wikipedia

Advantages

On top of the strengths mentioned in the medical sonography entry, contrast-enhanced ultrasound adds these additional advantages:

The body is 73% water, and therefore, acoustically homogeneous. Blood and surrounding tissues have similar echogenicities, so it is also difficult to clearly discern the degree of blood flow, perfusion, or the interface between the tissue and blood using traditional ultrasound.[4]

Ultrasound imaging allows real-time evaluation of blood flow.[22]

Quantitative evaluation of microvascular blood flow by contrast-enhanced ultrasound (CEUS). C. Greis Published 2011 Medicine Clinical hemorheology and microcirculation

Destruction of microbubbles by ultrasound[23] in the image plane allows absolute quantification of tissue perfusion.[24]

Ultrasonic molecular imaging is safer than molecular imaging modalities such as radionuclide imaging because it does not involve radiation.[22]

Alternative molecular imaging modalities, such as MRI, PET, and SPECT are very costly. Ultrasound, on the other hand, is very cost-efficient and widely available.[10]

Since microbubbles can generate such strong signals, a lower intravenous dosage is needed, micrograms of microbubbles are needed compared to milligrams for other molecular imaging modalities such as MRI contrast agents.[10]

Targeting strategies for microbubbles are versatile and modular. Targeting a new area only entails conjugating a new ligand.

Active targeting can be increased (enhanced microbubbles adhesion) by Acoustic radiation force[25][26] using a clinical ultrasound imaging system in 2D-mode [27][28] and 3D-mode.[29]

“Disadvantages”

In addition to the weaknesses mentioned in the medical sonography entry, contrast-enhanced ultrasound suffers from the following disadvantages:

Micro-bubbles don’t last very long in circulation. They have low circulation residence times because they either get taken up by immune system cells or get taken up by the liver or spleen even when they are coated with PEG.[10]

Ultrasound produces more heat as the frequency increases, so the ultrasonic frequency must be carefully monitored.

Micro-bubbles burst at low ultrasound frequencies and at high mechanical indices (MI), which is the measure of the negative acoustic pressure of the ultrasound imaging system. Increasing MI increases image quality, but there are tradeoffs with microbubble destruction. Microbubble destruction could cause local microvasculature ruptures and hemolysis.[9]

With increasing acoustic pressure (mechanical index = MI) the microbubbles start to oscillate in the ultrasound beam. At higher MI oscillation is getting more and more intense with pulsations in multiple axes until the shell of the microbubble ruptures and the gas content escapes. Microbubble destruction increases with higher insonation power and longer insonation time (longer persistence in the insonation field). Courtesy of Bracco – Christian Greis

Targeting ligands can be immunogenic, since current targeting ligands used in preclinical experiments are derived from animal culture.[9]

Low targeted microbubble adhesion efficiency, which means a small fraction of injected microbubbles bind to the area of interest.[16] This is one of the main reasons that targeted contrast-enhanced ultrasound remains in the preclinical development stages.