一般藥物的開發與測試常使用小動物模型評估效果，高頻超音波(>10 MHz)對比造影系統可提供小動物影像較高之空間解析度與靈敏度。然而，受限於一般商用對比劑的共振頻率在2-3 MHz，高頻超音波對比造影的空間解析度與靈敏度較為低弱。為解決前述問題，本研究提出振幅調變啾聲造影技術，提升高頻超音波系統下偵測對比劑的效能。此技術使用二種頻率不同的訊號，以中心頻率為9 MHz的低頻弦波訊號改變對比劑的聲學作用截面；以中心頻率為31.5 MHz的高頻啾聲訊號進行高解析度造影。共振的對比劑使得高頻啾聲散射訊號產生周期性變化，生成中心頻率為22.5 MHz的調變啾聲訊號。調變啾聲訊號以帶通濾波器區別組織與微氣泡的訊號差異，最後以壓縮濾波器修復空間解析度，達到提升訊雜比與對比解析度的目的。本研究使用仿體實驗估算振幅調變啾聲、二倍頻諧波與超諧波影像的對比解析度差異，並配合自製微氣泡作為對比劑使用。自製微氣泡是脂質外殼包覆八氟丙烷所構成，氣泡在溶液中的含量為4.1 × 1011/ml，粒徑為0.1 至 2.4 μm，共振頻率峰值為7.5 MHz。實驗所使用的仿體內部挖製一無壁面的通道，直徑為0.5 mm，通道內灌流稀釋10000倍的自製微氣泡。仿體實驗結果顯示，在相同軸向解析度的條件下，振幅調變啾聲造影相對於傳統二倍頻與超諧波造影可提升 3–14 dB的對比解析度，脈衝壓縮可以使得影像的對比解析度由7 dB提升至13 dB。由實驗結果可知振幅調變啾聲造影具有較好的消除組織訊號能力，可將造影頻率提升至30–50 MHz，具有進行高解析度超音波分子造影的潛力。

Small animal models have been widely used in drug development and testing. The high-frequency (> 10 MHz) contrast-enhanced ultrasound imaging system provides higher spatial resolution and imaging sensitivity. Nevertheless, nonlinear contrast detection generally suffers from the lower sensitivity at high frequency ultrasound due to the fact that most commercial contrast agents are originally designed to resonate at lower frequencies ranging from 2-3 MHz. To overcome the problem as mentioned above, we proposed an amplitude-modulation chirp imaging (AMCI) method for bubbles detection at high frequency ultrasound. The low-frequency tone burst (pumping wave) was used to manipulate the acoustic cross section of the ultrasound contrast agents (UCAs), and the high-frequency chirp (imaging wave) was used for high-resolution contrast imaging. Here, a pumping wave of 9 MHz is combined with a imaging wave of 31.5 MHz. The changes of acoustic cross section of the UCAs result in periodic changes in the amplitude of the backscattered chirp signal, forming amplitude-modulated chirp terms of 22.5 MHz. The chirp component is then extracted by a band-pass filter (BPF). Then a compression filter is used to recover axial resolution, and even further improve the signal-to-noise ratio (SNR) and contrast-to-tissue ratio (CTR). In vitro measurements were performed to evaluate the CTR values by using AMCI, traditional second- and ultra-harmonic imaging techniques. The self-made microbubbles used in these measurements were composed of C3F8 gas core encapsulated by a lipid shell. The microbubbles concentration was 4.1 × 1011/ml and the size distribution was ranging from 0.1 to 2.4 μm. The peak resonance frequency occurs around 7.5 MHz. Embedded in the phantom was a wall-less vessel of 0.5-mm diameter in which the self-made microbubbles in 1:10000 dilution were flowing. The results indicate that AMCI can provide 3 to 14 dB more agent-to-tissue contrast than those in traditional second- and ultra-harmonic imaging techniques and with a similar axial resolution. The CTR rises from 7 dB to 13 dB after using pulse compression technique. The results show that AMCI technique also performed a better ability of tissue suppression in the phantom experiments. Potential applications include increasing operating frequency of imaging wave to 30-50 MHz to achieve a higher spatial imaging resolution and applying the AMCI in ultrasound molecular imaging.

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