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The physics of Contrast Imaging

An introduction to contrast

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Ultrasound contrast agents (UCAs) consist of acoustically-active gas-filled microspheres which are designed to increase the signal strength of ultrasound waves (echoes). As they remain intravascular at all times, they act effectively as red blood cell tracers. The microbubbles consist of an outer shell encapsulating an inner gas. The 1st generation agents (inner gas was air) were safe but dissipated too quickly to be of clinical value. 2nd generation agents consist of an inert gas which has high density, high molecular weight and low solubility. A thicker outer shell confers greater stability and these changes to both the inner gas and outer shell have improved the durability of the bubbles, ensuring they can cross the pulmonary capillary bed and reach the left ventricular cavity intact in order to enhance the ultrasonic signal.


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Understanding the interaction between contrast agents & ultrasound is fundamental if one wishes to learn contrast echocardiography from its basic principles. The figure below helps to illustrate the difference between how tissue and microbubbles respond to ultrasound waves:

Contrast Echo Box: Introduction

  • TISSUE: Incident frequency results in equal and opposite vibration (i.e. LINEAR RESPONSE)
  • MICROBUBBLES: Can only become so small but can expand to a greater degree, resulting in unequal oscillation (i.e. NON-LINEAR RESPONSE)
  • This results in asymmetrical vibrations which produce harmonic frequencies

The frequency at which sound waves leave the transducer is known as the fundamental frequency. The ultrasound waves become distorted on passing through the body as they encounter tissues of differing composition and density. This changes the waveform and generates frequencies different from the incident frequency. These are harmonic frequencies, often shortened to harmonics. Harmonic frequencies include sub-harmonic, ultraharmonic and multiples of the fundamental frequency. The strongest harmonic signals are multiples of the fundamental frequency.

Contrast Echo Box: IntroductionFigure: Graph demonstrating the additional – harmonic – frequencies generated when using ultrasound contrast agents.


Tissues and microbubbles differ in behaviour depending upon the power of the signal they are exposed to – this is usually expressed as the MECHANICAL INDEX. The mechanical index is described in more detail in the next section (on machine settings). The diagram below illustrates the differential response of tissue and microbubbles in relation to varying mechanical index:

Contrast Echo Box: Introduction

As MI increases, tissue harmonics increase. Harmonics from microbubbles are greatest with an intermediate MI, as at higher MI the bubbles become unstable and are destroyed. This does produce a burst of harmonics, but the bubbles are irreversibly damaged and can no longer oscillate and thus generate further harmonic signals (i.e. they cannot continue to enhance the image)

The figure below illustrates a typical acoustic field. Higher amplitude sound produces more harmonics. Therefore, the harmonic energy is concentrated in the center of the beam where the sound energy is the highest in amplitude. Note that there is very little harmonic energy in the near field. This is because the beam has not yet become sufficiently focused to be of a high intensity.

Contrast Echo Box: Introduction

Consequently, as depth of imaging increases, the fundamental signal decreases whilst the harmonic signal strength increases. It is apparent that, even without contrast agents, tissues do generate some harmonic signals which are strongest in the mid-field of the ultrasound beam. This results in improved image resolution because the ‘noise’ predominantly originating from fundamental signals is eliminated – thus the LV cavity appears uniformly dark contrasting with tissue, which appears bright.

Selectively filtering out the fundamental frequency allows transducers to receive only the harmonic frequency. The benefits of this include:

  • Reduced near-field artefacts / noise
  • Improved endocardial delineation due to enhanced resolution
  • Combination of penetration power of a low frequency with improved image quality of a second harmonic-generated image

Contrast Echo Box: Introduction

An example of improved visualisation of endocardial borders when using harmonic imaging (right) as opposed to fundamental imaging only (left)

Disadvantage of Tissue Harmonic Imaging

Contrast Echo Box: Introduction

Thus in very thin individuals, where the transducer is in very close proximity to the heart, the near field is almost entirely composed of fundamental frequencies and hence the apex is often inadequately visualized. Conversely, in obese patients, the very far field will also have poor harmonics and thus poor image resolution.

On the other hand, the ability of microbubbles to generate harmonic frequencies is much less depth-dependent compared to tissue. Thus, in order to improve image quality in such individuals where harmonic imaging alone is insufficient, ultrasound contrast agents should be utilised.

The properties of the ideal UCA are listed below:

  • High Echogenicity: strong ultrasound reflectors
  • Linear relationship between concentration and signal intensity
  • Ability to cross the pulmonary capillary bed     
  • Stability over the duration of the procedure  
  • Minimal imaging artefacts  
  • Ability for rapid disruption at higher power outputs  
  • Safety : Non toxicity  
  • Additional special properties (e.g. site-specific therapeutic drug delivery)

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