A novel ultrasound contrast agent (UCA) based on air-filled polymer-shelled microbubbles, is prepared within 3MiCRON project for multimodality approach covering ultrasound, MRI and SPECT investigation. These bubbles have thick, about 30% of the radius, shell providing greater stability and longer half life in a pulmonary circulation compare to commercially available phospholipid UCAs. In addition, extensive storage capacity and possibility to incorporate drugs or pharmacological relevant materials are inherited to these bubbles.
Understanding the behavior of the UCA under ultrasound exposure is paramount to the proper and total exploitation of all unique features that these gas-filled microdevice offers. Even though, thickness of the polymeric shell is considerably higher than of commercial UCAs, the enhancement of backscattered power of about 25 dB produced from suspension insonified at low pressure (100 kPa) was observed. It should be noted that thick polymer shell could still be disrupted by high pressure (1 MPa) ultrasonic pulse. Nevertheless, diagnostic imaging typically utilizes the intermediate pressure level, where nonlinear oscillation of the microbubbles give rise to harmonic component in the received echo. It was observed that at pressure level of 400 kPa, Pulse Inversion (PI) technique fail to distinguish between the regions filled with polymer UCA and surrounding ultrasound phantom, mimicking liver tissue.
In this paper, a coded excitation technique is proposed to characterize the non-linear properties of the polymer-shelled microbubbles in vitro at intermediate pressure. For a decade ago, coded excitation technique has been adopted into the ultrasound scanners in order to increase the signal-to-noise ratio (SNR) and penetration depth, while matching filters compensates the decrease in axial resolution. In the proposed method, a time domain signal is modulated by a several window functions (e.g. Blackman-Harries, Hanning, Hamming, and Kaiser-Bessel) with or without linear chirp pulses constructed for experiments in vitro.
Our preliminary results suggest that coded excitation technique offers an increase of approximately 15dB in contrast-to-tissue ration (CTR) compared to the result achieved from a commercially available Pulse Inversion technique.
In conclusion, proposed polymer-shelled microbubbles provide a viable system to be used among the next generation of UCAs, and in combination with improved signal handling is superior not only in image enhancement relevant to diagnostics but also in localized and specific drug delivery for non-invasive therapy.