**1.4.2.2 Contrast Enhanced Ultrasound (CEUS)**

The introduction of intravenous (i.v.) contrast agents (CAs) is a great step forward for ultrasound. The first attempts to contrast ultrasound emerged in the '60s and had applications in interventional cardiology. After the 90s, first generation contrast agents were introduced into the clinical practice (the most used product is Levovist, Schering AG). These are air containing microbubbles, wrapped in a stabilizing membrane with the property to enhance the intensity of the echoes received from the blood flow thus making the Doppler signal more evident. This type of CAs has the disadvantage of a "blooming" effect of the color on CFM examination which masks the information derived from the microcirculation. With the development of transducer technology and the introduction of intermittent pulses emission with high mechanical index (MI> 0.2) it was possible to detect slow flows by identifying signals resulting from "breaking" microbubbles. This technique, called "destructive" contrast ultrasound is similar to that of contrast CT or MRI. Its disadvantage is that information cannot be obtained in "real time". After the year 2000, second generation contrast agents were introduced in clinical practice [SonoVue® in Europe, SonazoidTM in Japan, Definity in Canada, OptisonTM). They consist of microbubbles filled with different gases other than air, with stability and elasticity in the bloodstream higher than that of the first generation CAs. The exposure of these CAs to low mechanical index (MI <0.1 to 0.2) US generates harmonics echoes resulting from non linear microbubble oscillation (table 1).


Table 1. Characteristics of second generation contrast agents. Particularities and importance.

As low acoustic power US are used, this procedure does not break the microbubbles, which allows "real time" blood flow examination during several minutes (Burns & Wilson, 2006).

Harmonic contrast US examination, using second generation CAs requires special software equipment which suppresses 2D ultrasound image derived from the tissues by inverted phase ultrasound emission (the technique is called "pulse inversion"). In this way the information on the screen will correlate only to harmonic echoes generated by the microbubbles (Burns et al, 2000).

CEUS examination is a qualitative examination. As it is a continuous exploration, CEUS allows successive identification of vascular phases: arterial (approximately 10 - 15 sec. from

The introduction of intravenous (i.v.) contrast agents (CAs) is a great step forward for ultrasound. The first attempts to contrast ultrasound emerged in the '60s and had applications in interventional cardiology. After the 90s, first generation contrast agents were introduced into the clinical practice (the most used product is Levovist, Schering AG). These are air containing microbubbles, wrapped in a stabilizing membrane with the property to enhance the intensity of the echoes received from the blood flow thus making the Doppler signal more evident. This type of CAs has the disadvantage of a "blooming" effect of the color on CFM examination which masks the information derived from the microcirculation. With the development of transducer technology and the introduction of intermittent pulses emission with high mechanical index (MI> 0.2) it was possible to detect slow flows by identifying signals resulting from "breaking" microbubbles. This technique, called "destructive" contrast ultrasound is similar to that of contrast CT or MRI. Its disadvantage is that information cannot be obtained in "real time". After the year 2000, second generation contrast agents were introduced in clinical practice [SonoVue® in Europe, SonazoidTM in Japan, Definity in Canada, OptisonTM). They consist of microbubbles filled with different gases other than air, with stability and elasticity in the bloodstream higher than that of the first generation CAs. The exposure of these CAs to low mechanical index (MI <0.1 to 0.2) US generates harmonics echoes resulting from non linear microbubble oscillation (table 1).

**Particularity Importance** 

through respiration and breakage Can be used in renal and hepatic failure

interest.

echoes

time" Table 1. Characteristics of second generation contrast agents. Particularities and importance.

As low acoustic power US are used, this procedure does not break the microbubbles, which allows "real time" blood flow examination during several minutes (Burns & Wilson, 2006). Harmonic contrast US examination, using second generation CAs requires special software equipment which suppresses 2D ultrasound image derived from the tissues by inverted phase ultrasound emission (the technique is called "pulse inversion"). In this way the information on the screen will correlate only to harmonic echoes generated by the

CEUS examination is a qualitative examination. As it is a continuous exploration, CEUS allows successive identification of vascular phases: arterial (approximately 10 - 15 sec. from

They are real angiospecific tracers useful for quantification of circulation in a region of

High persistence and prolonged investigation

Ultrasound information is found in harmonic

Ultrasound exploration is dynamic, "in real

**1.4.2.2 Contrast Enhanced Ultrasound (CEUS)** 

They do not cross vessel walls, being strictly confined to the circulatory

recirculation from the large to small circulation until complete clearance

Elimination of contrast agent is made

They show a non-linear oscillation when exposed to low MI ultrasounds

microbubbles (Burns et al, 2000).

Characterized by repeated

bed.

the time of injection in the peripherals up to approx. 30-40 seconds) and venous. Some circulation areas (liver, spleen) have a "late" phase due to the "capture" of microbubbles into the reticulo-histiocyte system (RHS). In addition, the investigation also allows the assessment of vascular morphology which provides information similar to angiography. CEUS investigation has a high temporal resolution, superior to CT or MRI explorations.

CEUS liver investigation has two important elements that make it distinct (Cosgrove, 2007; Claudon et al, 2008):


A useful procedure to obtain more quantitative details is contrast curves analysis. These consist of graphical representation of the CA dynamics while crossing a region of interest. The method is useful for assessing chemotherapy efficacy in various malignancies.

Fig. 1. Contrast dynamic analysis curves in the region of interest - TIC. Tracer dynamics in the region of reference is marked with blue and with yellow in the region of interest (tumor). It can be seen that the tumor has a more abundant circulation than the surrounding liver parenchyma.

*Limitations of CEUS examination*. Harmonic contrast examination has some limitations including: a) the procedure is indicated only correlated with good 2D image; b) it has a relatively high cost; c) it is operator dependent examination.
