In conventional ultrasound technology B-Mode can provide anatomical information and (Colour) Doppler can visualize larger vessels (macrovascular system) based on velocity information of blood flow in the intravascular lumen.

The visualization of blood flow in the microvascular system (small vessels and capillaries) with flow velocities below tissue movements and transducer movements and no consistent flow direction is not possible with Doppler techniques. To demonstrate such microvascular blood flow and in particular to discriminate the different arrival times in specific areas of parenchymal tissue (e.g. focal lesions) direct imaging of a tracer is needed, allowing to assess at which time point the tracer arrives (e.g. in the arterial or portal-venous phase in the liver), how long the tracer stays in the tissue and how fast it is washed-out ¹.

For ultrasound imaging examination microscopically small microbubbles are used as tracer. After intravenous injection, the microbubbles follow the flow and distribution of red blood cells ¹.

After arrival in the right heart chambers and crossing of the pulmonary circulation the microbubbles arrive in the left heart chambers, resulting in an intense opacification of the left ventricle (LVO). Depending from the LV heart function the microbubbles are ejected into the arterial circulation, demonstrating blood flow and distribution through arterial vessels (macrovasculature) into the parenchymal organs (e.g. liver, breast).

In the liver, delivery of microbubbles occurs via two supplying systems: hepatic artery and portal vein (dual blood supply). Since the blood flowing through the portal vein has a longer delivery pathway (first crossing the gastrointestinal circulation) it arrives at a later timepoint, so that two different wash-in phases can be discriminated (arterial and portal phase).

The dynamic assessment of microbubble-enhanced blood flow and distribution is called Contrast-Enhanced Ultrasound (CEUS). CEUS has some intrinsic advantages compared to other imaging modalities:

• realtime imaging ²
  allowing continuous imaging of contrast enhancement profiles over 6-8 min with extremely high temporal resolution (about 15 to 60 images per second)
• bedside availability ^3,4
  allowing examinations at almost every location incl. intensive care units, surgical rooms, ambulatory units, ...
• fast contrast elimination ^5,10
  allowing follow-up examinations in short intervals (also in patients with renal impairment)
• lack of ionising radiation ⁶
  allowing repeated examinations over a long period of time (e.g. for chronic diseases)
• proven safety ^7,8
  ultrasound contrast agents are generally safe and have the lowest incidence of acute adverse reactions compared to other contrast agents
• favourable costs for liver imaging ⁹

References:

1. Greis C. Ultrasound contrast agents as markers of vascularity and microcirculation. Clin Hemorheol Microcirc 2009; 43: 1-9
2. Piscaglia F, Lencioni R, Sagrini E, Pina CD, Cioni D, Vidili G, Bolondi L.. Characterization of focal liver lesions with contrast-enhanced ultrasound. Ultrasound in Med & Biol 2010; 36: 531-550
3. Loss M, Schneider J, Uller W, Wiggermann P, Scherer MN, Jung W, Schlitt HJ, Stroszczynski C, Jung EM. Intraoperative high resolution ultrasound (IOUS) for detection of microvascularisation of malignant liver lesions before surgery or radiofrequency ablation. Clin Hemorheol Microcirc 2012; 50: 65-77
4. Schulz A, Dormagen JB, Drolsum A, Bjørnbeth BA, Labori KJ, Kløw NE. Impact of contrast-enhanced intraoperative ultrasound on operation strategy in case of colorectal liver metastasis. Acta Radiol 2012; 53: 1081-1087
5. Morel DR, Schwieger I, Hohn L, Terrettaz J, Llull JB, Cornioley YA, Schneider M. Human pharmacokinetics and safety evaluation of SonoVue, a new contrast agent for ultrasound imaging. Invest Radiol 2000; 35: 80-85
6. Jacob J, Deganello A, Sellars ME, Hadzic N, Sidhu PS. Contrast enhanced ultrasound (CEUS) characterization of grey-scale sonographic indeterminate focal liver lesions in pediatric practice. Ultraschall Med 2013; 34: 529-540
7. ESUR contrast media guidelines 9.0. www.esur2015.org
8. Claudon M, Dietrich CF, Choi BI, Cosgrove DO, Kudo M, Nolsøe CP, Piscaglia F, Wilson SR, Barr RG, Chammas MC, Chaubal NG, Chen MH, Clevert DA, Correas JM, Ding H, Forsberg F, Fowlkes JB, Gibson RN, Goldberg BB, Lassau N, Leen EL, Mattrey RF, Moriyasu F, Solbiati L, Weskott HP, Xu HX. Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver - Update 2012. Ultraschall in Med 2013; 34: 11–29
9. National Institute for Health and Clinical Excellence (NICE). SonoVue (sulphur hexafluoride microbubbles) - contrast agent for contrast enhanced ultrasound imaging of the liver. NICE diagnostics guidance 5, www.nice.org.uk
10. Laura V. Klotz, Robert Gürkov, Martin E. Eichhorn, Vanessa Siedek, Eike Krause, Karl-Walter Jauch, Maximilian F. Reiser, Dirk-Andre Clevert. Perfusion characteristics of parotid gland tumors evaluated by contrast-enhanced ultrasound. European Journal of Radiology Dec 2013; 82: 2227–2232