**2. Principles**

Ultrasound contrast agents are gas-filled microbubbles and are used clinically as blood pool tracers to significantly enhance the acoustic backscatter from blood. Definity (Lantheus Medical Imaging, North Billerica, MA, USA) and SonoVue (Bracco S.P.A., Milan, Italy) are two clinically licensed ultrasound contrast agents. MicroMarker (targeted and untargeted) (Bracco, Geneva, Switzerland; VisualSonics, Toronto, ON, Canada) is marketed as a preclinical UCA for contrast enhancement and molecular imaging in small animals. The microbubbles are made up of a lipid coating and a gaseous content (sulfur hexafluoride). The substance has a much lower solubility than air, which gives it good blood balance [3]. The diameter of the microbubbles is similar to that of the red blood cells (7 microns), which allow the passage of the contrast agent through the pulmonary and peripheral capillary circulation without any impediment. One of the main physic principles relies on the compressibility of the gases exposed to the pressure of an ultrasound beam. Microbubbles generate (through the mechanism called "non-linear vibration") harmonic echoes (higher frequency multiples) that are recorded by the transducer. This behavior is significantly different from that of tissues. Ultrasound devices use ultrasound emissions to cancel the tissue signals and to accentuate the microbubble signals.

After intravenously administration of the contrast agent, an increased intensity signal coming from the vessels is depicted on the ultrasound screen. This enhanced signal can be evaluated in the gray scale, in the color-coded modes or in the hybrid mode (the combination of the two). The CEUS technique has a dynamic character, being possible a continuous tracking of the contrast agent through a region of interest (ROI). In the case of the kidney, the contrast agent is initially visualized in the renal artery, progressing to the sinus, the renal cortical, and after a delay of several seconds to the renal medulla. The first 30–40 s (sec) postinjection is appropriate for the arterial phase and then 30–40 s for the venous phase [4] (**Figure 1**).

The CEUS examination might be focused on a region of interest (ROI). The operator might analyze this ROI in real time, during the examination or through a dedicated soft that traces the time-intensity curves. The parameters obtained describe the vascular and temporal behavior, depending on the different postadministration phases (<30–40 sec = arterial time; >30– 40 sec = venous time). The time-intensity curve (TIC) represents a quantitative analysis of the variability of the mean intensity within the selected sample over a period of time (**Figure 2**). They can be postprocessed on any video clip saved during CEUS [5].

"conventional" ultrasound was optimized by numerous procedures, including those using "contrast agents." It consists of intravenous administration of specific substances in order to improve the diagnostic information. The technique is called "contrast-enhanced ultrasound" (CEUS). It allows simultaneously visualization of the flows from the large vessels and from the microcirculation [1]. CEUS is independent of the characteristics of blood column movement (velocity and angle of incidence of the ultrasound beam), being more sensitive than the Doppler technique. It permits the study of capillary circulation and detection of blood

The CEUS method was first used for hepatic tumor pathology, but also for abdominal emergencies (detection of infarct or parenchymal dilacerations). The indication of CEUS has evolved and expanded rapidly in recent years, with the development of new contrast agents as well as the identification of new directions called "clinical applications" [2]. In urology, CEUS may have clinical implications with diagnostic values added to the detection and char-

Ultrasound contrast agents are gas-filled microbubbles and are used clinically as blood pool tracers to significantly enhance the acoustic backscatter from blood. Definity (Lantheus Medical Imaging, North Billerica, MA, USA) and SonoVue (Bracco S.P.A., Milan, Italy) are two clinically licensed ultrasound contrast agents. MicroMarker (targeted and untargeted) (Bracco, Geneva, Switzerland; VisualSonics, Toronto, ON, Canada) is marketed as a preclinical UCA for contrast enhancement and molecular imaging in small animals. The microbubbles are made up of a lipid coating and a gaseous content (sulfur hexafluoride). The substance has a much lower solubility than air, which gives it good blood balance [3]. The diameter of the microbubbles is similar to that of the red blood cells (7 microns), which allow the passage of the contrast agent through the pulmonary and peripheral capillary circulation without any impediment. One of the main physic principles relies on the compressibility of the gases exposed to the pressure of an ultrasound beam. Microbubbles generate (through the mechanism called "non-linear vibration") harmonic echoes (higher frequency multiples) that are recorded by the transducer. This behavior is significantly different from that of tissues. Ultrasound devices use ultrasound emissions to cancel the tissue signals and to accentuate

After intravenously administration of the contrast agent, an increased intensity signal coming from the vessels is depicted on the ultrasound screen. This enhanced signal can be evaluated in the gray scale, in the color-coded modes or in the hybrid mode (the combination of the two). The CEUS technique has a dynamic character, being possible a continuous tracking of the contrast agent through a region of interest (ROI). In the case of the kidney, the contrast agent is initially visualized in the renal artery, progressing to the sinus, the renal cortical, and after a delay of several seconds to the renal medulla. The first 30–40 s (sec) postinjection is appropriate for the arterial phase and then 30–40 s for the venous

acterization of focal and diffuse renal, prostatic, testicular, and bladder lesions.

extravasations.

120 Evolving Trends in Kidney Cancer

**2. Principles**

the microbubble signals.

phase [4] (**Figure 1**).

Other qualitative useful information is represented by: the intensity of fill-in with contrast agent, the sense of fill-in, the fill-in pattern, the degree of wash-out of the contrast agent, the sense of wash-out, and the pattern of wash-out [6]. The evaluation of the lesions of interest is carried out as compared to the normal parenchyma.

**Figure 1.** CEUS evaluation of the kidney. In very short time, there is a replenishment with microbubbles of cortex (periphery), cortex (columns), and the medulla.

**Figure 2.** Representation of time-intensity transit curves. A sample area mounted in a specific area considered "target." Special software is representing the characteristics of perfusion.
