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Microbubble ultrasound contrast agents: an update

  • Ultrasound
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Abstract

Microbubble contrast agents for ultrasound (US) have gained increasing interest in recent years, and contrast-enhanced US (CEUS) is a rapidly evolving field with applications now extending far beyond the initial improvements achieved in Doppler US. This has been achieved as a result of the safe profile and the increased stability of microbubbles persisting in the bloodstream for several minutes, and also by the availability of specialized contrast-specific US techniques, which allow a definite improvement in the contrast resolution and suppression of signal from stationary tissues. CEUS with low transmit power allows real-time scanning with the possibility of prolonged organ insonation. Several reports have described the effectiveness of microbubble contrast agents in many clinical applications and particularly in the liver, spleen, and kidneys. CEUS allows the assessment of the macrovasculature and microvasculature in different parenchymas, the identification and characterization of hepatic and splenic lesions, the depiction of septal enhancement in cystic renal masses, and the quantification of organ perfusion by the quantitative analysis of the echo-signal intensity. Other fields of application include the assessment of abdominal organs after traumas and the assessment of vesico-ureteral reflux in children. Finally, tumor-targeted microbubbles make possible the depiction of specific biologic processes.

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  1. Department of Radiology, Cattinara Hospital, University of Trieste (Italy), Strada di Fiume 447, Trieste, 34149, Italy

    Emilio Quaia

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Correspondence to Emilio Quaia.

Appendix-Mathematical models for parenchymal perfusion quantitation

Appendix-Mathematical models for parenchymal perfusion quantitation

The negative exponential function [69] has the form \({\text{y = A}}{\left( {{\text{1 - e}}^{{{\text{ - $ \alpha $ t}}}} } \right)} + {\text{C}}\), where A= the amplitude of the curve above baseline, α= the initial slope of the curve, and C= the intensity at baseline (the zero crossing point of the y-axis), and it is based on a single compartment model. The slope of the first ascending curve is related to microbubble velocity, while the plateau phase is related to fractional blood volume. Limitations of this model include the assumption of a constant concentration of microbubbles entering the region of interest (ROI) immediately after the destruction pulse and the neglect of the different directions of the vessels inside the examined ROI.

The sigmoid function [70] describes a curve with a low initial slope that increases secondarily to an inflexion point and has the form of \( C_{n} {\left( t \right)} = \frac{{C_{0} }} {{{\left( {1 + \tau \lambda } \right)}^{n} }} \times {\left[ {1 - {\left( {1 + {\sum\limits_{i = 1}^{n - 1} {\frac{{\beta ^{i} t^{i} }} {{i!}}} }} \right)}e^{{ - \beta t}} } \right]} \), where Cn(t) is the refilling evolution of the microbubble concentration in an ROI, C0 is the concentration of microbubbles in blood vessels that enter the ROI (number of microbubbles per liter), which is assumed to be constant with time, t is time, λ represents the fraction of microbubbles destroyed by the US beam per second, which is assumed to be constant, 1/τ = F/Vb where F is the rate of the inflow (equals to the rate of outflow) and Vb is the volume of flow in the ROI, and β is (1 + τλ)/τ. This model is based on the assumption that microbubble destruction actually occurs in the feeding vessels that reach the ROI and that microbubbles present a constant concentration in the circulation.

The multivessel model [71, 72] takes into account the different directions and different amounts of blood flow that are found in vessels inside the ROI. After the microbubble destruction by high transmit power insonation, the replenishment is initially linear with time. Once the vessels in the ROI that are perpendicular to the US section and that demonstrate the maximum blood flow velocity of all vessels are completely refilled, a nonlinear increase in echo-signal intensity occurs and is followed by saturation to maximum. The blood volume is then proportional to the maximum plateau of the replenishment curve, and the blood flow velocity (v) can be obtained as \( v = {d \times m} \mathord{\left/ {\vphantom {{d \times m} {{\left( {2 \mathord{\left/ {\vphantom {2 3}} \right. \kern-\nulldelimiterspace} 3\,\max } \right)}}}} \right. \kern-\nulldelimiterspace} {{\left( {2 \mathord{\left/ {\vphantom {2 3}} \right. \kern-\nulldelimiterspace} 3\,\max } \right)}} \), where d is the US beam width, m is the slope of the initial linear increase of the replenishment curve starting at zero, and max is the maximum of the replenishment curve.

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Quaia, E. Microbubble ultrasound contrast agents: an update. Eur Radiol 17, 1995–2008 (2007). https://doi.org/10.1007/s00330-007-0623-0

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