ULTRASOUND CONTRAST AGENTS - BASIC PRINCIPLES

Introduction. Ultrasonography lacked substances to be administered to patients to improve or increase the diagnostic yield, which is peculia r considering that contrast agents have long been used with all the ot her imaging techniques. Fortunately some contrast agents, most of them consisting in gas microbubbles, have been recently introduced for ult rasound imaging too: this review will focus on their history, behavior , current applications and future developments. Echocontrast agent res earch is in progress and many new agents are expected to be marketed t his and next year, to be added to Leovist(TM) by Schering AG (Berlin, Germany), to enhance the ultrasound signal safely and effectively. No definitive conclusions can be drawn yet on the actual merits of each c ontrast agent, but all of them seem to be both effective and safe, mea ning that their future success will depend on the relative cost-effect iveness and peculiarities. The basic principles of echocontrast agents . The microbubbles act as echo-enhancers by basically the same mechani sm as that determining echo-scattering in all the other cases of diagn ostic ultrasound, namely that the backscattering echo intensity is pro portional to the change in acoustic impedance between the blood and th e gas making the bubbles. The different acoustic impedance at this int erface is very high and in fact ah of the incident sound is reflected, even though not all of it will of course go back to the transducer. B ut the acoustic wave reflection, though nearly complete, would not be sufficient to determine a strong US enhancement because the microbubbl es are Very small and are sparse in the circulation. Moreover, reflect ivity is proportional to the fourth power of a particle diameter but a lso directly proportional to the concentration of the particles themse lves. Second harmonic imaging. As we said above, the microbubbles reac hed by an ultrasound signal resonate with a specific frequency dependi ng on microbubble diameter. However, the main resonance frequency is n ot the only resonance frequency of the bubble itself and multiple freq uencies of the fundamental one are emitted, just like in a musical ins trument. These harmonic frequencies have decreasing intensity, but the second frequency, known as the second harmonic, is still strong enoug h to be used for diagnostic purposes. The theoretical advantage of the harmonic over the fundamental frequency is that only contrast agent m icrobubbles resonate with harmonic frequencies, while adjacent tissues do not resonate, or else their harmonic resonation is very little. Th us, using a unit especially set to produce ultrasounds at a given freq uency (3.5 MHz) and receive an ultrasound signal twice as powerful (7 MHz) it will be possible to show the contrast agent only, without any artifact from the surrounding anatomical structures, with a markedly i mproved signal-to-noise ratio. A similar effect to digital subtraction in angiography dan thus be obtained, even though through a totally di fferent process. Moreover, second harmonic imaging permits to show ext remely small vessels (down to 40 mu m) with very slow flow, which woul d be missed with a conventional method. B-mode imaging can also depict the microbubbles in the myocardium suppressing nearly all the artifac ts from cardiac muscle motion. Recently a peculiar behavior of microbu bbles has been observed which may permit contrast agent detection even in capillaries. This method is variously known as sonoscintigraphy, l oss of correlation, stimulated acoustic emission and transient scatter ing. The contrast agent microbubbles reached by an ultrasound beam pow erful enough explode producing a strong and very short backscatter ech o which is read by the unit as a Doppler signal and results in a color pixel where the individual microbubble exploded. Conclusions. The mic robubble contrast agents developed and introduced as safe and effectiv e echo-enhancers in present-day clinical practice will open up new opp urtunities and result in an amazing revolution of ultrasonography as w e know it now. (C) 1998 Elsevier Science Ireland Ltd. All rights reser ved.