1. Ultrasonic Imaging Using Contrast Agents

2. Introduction
Contrast agents are used to provide higher contrast. The three commonly seen contrast agents are backscatter, attenuation and sound velocity.
Contrast agents could be solid particles, emulsion, gas bubbles, encapsulated gas, or liquid.

3. Introduction Primary clinical benefits:
Enhanced contrast resolution between normal and diseased tissues.
Outline of vessels or heart chambers.
Tissue characterization by using tissue specific agents.
Increasing blood flow signals.
Dynamic study using washout curve.

4. Example

5. Clinical Applications: Cardiology
Endocardial border detection.
Left ventricle (LV) function.
Valvular regurgitation quantification.
LV flow patterns.
Perfusion area of coronary artery.
Assessment of surgery for ventricular septal defect.

6. Clinical Applications: Others
Liver tumor enhancement.
Uro-dynamics and kidney functions.
Tubal function and placenta perfusion.
Transcranial Doppler enhancement.
LV pressure measurements.

7. Current Contrast Agents
Echovist.
Albunex.
Levovist.
Echogen.
Quantison.
Many more,…

8. Contrast Mechanisms Strong backscattering produced by air bubbles.
The backscatter increases roughly linearly with the number of micro-bubbles.
A bubble in liquid acts as a harmonic oscillator. Acoustic resonance provides the major echo enhancement. In addition, strong harmonics are produced.

9. Contrast Mechanisms
Acoustic attenuation of soft tissues is typically represented by a constant (e.g., 0.5dB/cm/MHz).
Since contrast agents significantly change the scattering properties, attenuation measurements can also be used for contrast enhancement.

10. Contrast Mechanisms
Sound velocity is primarily determined by density and compressibility. Apparently, micro-bubble based contrast agents alter sound velocity.
Contrast enhancement based on sound velocity variations is still academic.

11. Contrast Mechanisms
Micro-bubbles produce strong harmonics when insonified near the resonance frequency.
If such harmonics are stronger than tissue harmonics, contrast can be improved.
Second harmonic signal is most useful due to limited transducer and system bandwidth.

12. Desired Characteristics of Contrast Agents
Efficient backscattering.
Small size for pulmonary transport.
Long half-life.
Low toxicity.
Possibility of attenuation contrast.
Possibility of speed of sound contrast.

13. Imaging Consideration
Low peak acoustic amplitude.
Low average acoustic power.
ECG triggering.
Frequency control.

14. System Requirements Transmitter: minimal harmonic signals.
Propagation: minimal harmonic generation.
Receiver: maximal fundamental rejection.

15. System Requirements Adequate dynamic range. Configurable beam former.
Sufficient system bandwidth.
Wide transducer bandwidth.

16. Imaging Techniques
The phasing pattern across the array can be varied to reduce the signals at a certain frequency.
Alternate phasing is applicable to contrast harmonic imaging.
Alternate phasing on transmit is not ideal.

17. Imaging Techniques Alternate phasing for receive:p
Alternate phasing for transmit
0.5p

18. Imaging Techniques
Difference imaging technique: contrast agents can be viewed as a “modulator”. When two different frequencies, say f1 and f2, are used on transmit, the contrast agents generate f1+f2 and f1-f2.
f1 and f2 can be properly chosen to increase the rejection ratio.

19. Imaging Techniques
Subtraction mode: Two pulses with different signs are transmitted consecutively. By adding two images together, linear components cancel while second order components remain.
This technique is susceptible to motion artifacts.

20. Pulse Inversion Doppler
An extension for the subtraction mode to Doppler imaging, i.e., pulse inversion with multiple firings.
There exists a nonlinear Doppler spectrum completely separate from the linear spectrum.
Potential increase in agent to tissue contrast.

21. Problems in Flow Estimation
Radiation force tends to move the contrast agents to a direction independent of the flow direction.
Bubble break down causes image artifacts.
Excessive backscatter produces “color blooming”.
Spectral broadening at high acoustic pressures.