Ultrasonic contrast agents are mostly liquids containing microbubbles with a diameter of 1~10um. They can be injected intravenously to various parts of the body (those related to the intestines can be administered orally). Due to the significant difference in the acoustic impedance characteristics of microbubbles and tissues, the diagnostic capability of fundamental wave ultrasound imaging can be enhanced, as shown in the figure below.

Sound waves propagate non-linearly through the microbubbles in the contrast agent, causing waveform distortion and a significant increase in harmonic components. In contrast, other tissues produce relatively few harmonics. The non-linear characteristics of microbubbles are used to increase the contrast between the contrast agent and tissues, improving the signal-to-noise ratio. However, the above is based on the assumption that tissue echoes are all linear. It is now certain that tissues can also produce harmonic signals originating from imaging, which can cause significant interference.

  When the sound pressure reaches a certain threshold and the emission frequency is twice the resonant frequency of the microbubbles, the microbubbles, in addition to producing second and higher-order harmonics, also produce subharmonics (f0/2, f0/3…) and ultraharmonics (3f0/2, 5f0/2), as shown in the figure below. The condition that the emission frequency is twice the resonant frequency of the microbubbles is to achieve better results. If the frequency does not meet this condition, subharmonics and ultraharmonics will still be produced, but the effect is not obvious. Tissues do not produce subharmonics and ultraharmonics. This further improves the contrast. At the same time, due to the high emission frequency, the axial resolution of the image can be improved. For the received low-frequency subharmonic signals, the echo attenuation is smaller, which is beneficial for the detection of deep tissues.

Application Examples

 Let's compare the effects of harmonic imaging through examples in some applications.
 The following figure shows that tissue harmonic imaging enhances the clarity of the endocardium and near-field resolution. Figure a shows fundamental wave imaging, and Figure b shows tissue harmonic imaging. It can be seen that the apical four-chamber view of tissue harmonic imaging is more obvious.

  The following figure shows parasternal long-axis images of the heart: (a) fundamental imaging, (b) harmonic imaging, and © pulse inversion harmonic imaging. It can be seen that tissue harmonic imaging reduces artifacts, while pulse inversion harmonic imaging further improves contrast and resolution.

  The following figure shows the enhancement of contrast agent intensity through second-harmonic imaging. The left image is fundamental frequency venous contrast agent imaging, and the right image is second-harmonic contrast agent imaging. It can be seen that the contrast is significantly enhanced using second-harmonic contrast agent imaging.

  The following figure shows an experiment using an 8mm vessel embedded in a phantom simulating tissue. Figure a is the fundamental wave image before contrast, Figure b is the fundamental wave image after contrast. Figure c is the subharmonic image before contrast, Figure d is the subharmonic image after contrast. Figure e is the harmonic image before contrast, and Figure f is the harmonic image after contrast. It can be seen that the contrast of the image after contrast is significantly higher than that before contrast. After using the contrast agent, the subharmonic image has better contrast than the harmonic image and is clearer. The contrast of the fundamental wave image after using the contrast agent is slightly worse than that of the harmonic image, and there are artifacts.
 

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