Page 427 - Libro 2

27 — Vascular Applications of Ultrasound Contrast Agents
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TISSUE-SPECIFIC AND TARGETED AGENTS
The kinetics of UCA microbubbles following an IV injection is complex, and each agent has its own unique characteristics.5 In general, after an IV administration, blood pool UCAs are contained exclusively in the body’s vascular spaces. When a vascular agent’s microbubbles are ruptured or oth- erwise destroyed, the microbubble shell products are metabolized or eliminated by the body, and the gas is exhaled.
Tissue-specific UCAs differ from vascular agents in that the microbubbles of these agents are removed from the blood pool and are taken up by or have an affinity toward specific tissues; for example, a thrombus or the reticuloendothelial system (RES) in the liver and spleen. Thus, to be clinically effec- tive, tissue-specific agents must possess two unique characteristics: an affinity for the targeted tissue and the ability to alter that tissue’s sonographic appear- ance. By changing the signal impedance (or other acoustic characteristics) of normal and abnormal tis- sues, these agents improve the detection of abnor- malities and can permit more specific sonographic diagnoses. Like blood-pool agents, tissue-specific UCAs are typically administered by an IV injection. Some tissue-specific UCAs also enhance the sono- graphic detection of blood flow so they can be used to improve the detection of flow as well as enhance targeted tissue. Because tissue-specific UCAs target specific types of tissues and their behavior is predict- able, they are considered molecular imaging agents.6
One type of tissue-specific UCA that is of particu- lar interest for vascular applications is a thrombus- specific agent.7 Although the administration of a blood-pool UCA can be used to better delineate the functional lumen of both arteries as well as veins, blood-pool agents do not directly enhance the sono- graphic appearance of thrombi. However, research is ongoing to develop UCAs that attach to fibrin, plate- lets, or other components of blood clots to enhance their sonographic detection.8
THERAPEUTIC AGENTS
Investigations are also ongoing in the development of UCAs that can be used for a variety of therapeutic ap- plications. Typically, therapeutic UCAs have a specific ligand or other binding moiety attached to their shell that has an affinity for a particular receptor (i.e., the target). Researchers have investigated the ability to enhance thrombolysis using acoustic energy with and without nontargeted UCA microbubbles. A significant amount of additional research has been performed us- ing thrombus-targeting UCAs that, when insonated, enhance thrombolysis (referred to as sonothrombol- ysis).9,10 This concept, if applied to the intracranial
vessels, potentially offers a noninvasive therapy for patients who suffer from embolic stoke.
CONTRAST-SPECIFIC EQUIPMENT MODIFICATIONS
Although microbubble-based UCAs can be used with conventional grayscale US and spectral Doppler to enhance the detection of blood flow, the clinical util- ity of UCAs is vastly improved by the use of so-called contrast-specific US software. Numerous investigations have been performed to better understand the com- plex interactions between acoustic energy (i.e., the US beam) and UCA microbubbles, which have, in turn, resulted in modifications to US instrumentation that is specifically designed to exploit these interactions.
HARMONIC IMAGING
Harmonic imaging (HI) can be performed with the same transducers used for conventional US. In HI mode, the US system is configured to receive only echoes at the second harmonic frequency, which is twice the transmit frequency (e.g., 6 MHz for a 3-MHz transducer).11,12 When subjected to the acous- tic energy present in the US field, UCA microbubbles oscillate in size (i.e., they get larger and smaller). The reflected echoes from the oscillating microbub- bles contain energy components at the fundamental frequency, as well as at higher and lower harmon- ics.13 In HI mode, the echoes from the oscillating mi- crobubbles have a higher signal-to-noise ratio than would be provided by using conventional US so that regions with microbubbles are more easily appreci- ated visually. Thus, contrast-specific HI provides a means to visualize contrast-enhanced blood flow and contrast-containing tissue using B-mode imag- ing. These modes obviate the need to use Doppler (which is susceptible to artifacts and other limita- tions) for the detection of blood flow. Most US equip- ment manufacturers now have available on their scanners some form of contrast-specific imaging modes, including simultaneous dual displays of the contrast-enhanced image and the conventional US image in real time (Fig. 27-2).
LOW MECHANICAL INDEX IMAGING AND INTERMITTENT IMAGING
During CES examinations, the energy present within the ultrasound beam can have a detrimental effect on contrast microbubbles.14 Contrast-specific imag- ing modes are designed to use low acoustic output power (as defined by the mechanical index [MI]) to avoid or minimize microbubble destruction.