過去的十年中，超音波分子生物影像在癌症相關領域的研究中被視為十分有潛力的一門技術，然而其造影技術仍有許多發展限制及尚待改進的空間。微氣泡標的性吸附於病灶區的效率低將降低影像對比解析度，另外傳統超音波分子影像演算法係以等待一段時間使自由氣泡自然代謝的方式來對標的性吸附的微氣泡進行成像，影像無法即時取得且容易受到移動的干擾而產生極大誤差。雖然目前已有相關研究提出以聲學輻射力來增加微氣泡吸附效率進而降低造影所需等待的時間，然而此技術的工作頻率較低導致前很難應用於高頻影像系統。
為了解決上述問題，本論文利用雙頻頻差激發技術以低頻的封包來提供聲學輻射力增加微氣泡吸附效率。本研究使用共振頻率為9–35 MHz的自製標的性吸附微氣泡進行實驗。結果顯示，當雙頻激發訊號封包頻率為靠近微氣泡共振頻率的10–30 MHz時，能使吸附效率在兩分鐘內增加達3.3–6.2倍。此外，由於高頻載波提供較小的空間取樣體積, 本技術可讓微氣泡做更局部的吸附，未來應用可進行局部治療，降低傷害其他正常組織之機會。
本論文的另一主軸，則是將雙頻激發訊號做更進一步的應用，配合啾聲調頻反向的技術，提出以雙頻啾聲調頻反向訊號做為一新式超音波分子生物影像造影訊號。此技術可以在一次的逆散射訊號中，將自由氣泡的訊號分離，保留下標的氣泡進行造影，因此可有效地縮短目前超音波分子生物影像造影技術的成像時間，進而達到即時的超音波分子生物影像造影。由於此訊號對於組織諧波訊號的高抑制能力以及可進行脈衝壓縮的特性，利用此技術所取得的標的影像對比解析度可達24.8 dB。

In the past decade, ultrasound molecular imaging has become a promising tool for cancer research, but there remain several challenges for its use in vivo. Low adhesion efficiency of microbubbles at the target sites decreases the contrast resolution of ultrasound molecular images. Conventional strategy to image the adherent microbubbles is based the clearance of freely circulating microbubbles after a period of time, which limits the development of real-time ultrasound molecular imaging. Motion artifacts may therefore affect the quality of acquired images. Thus, ultrasound radiation force (USRF) was recently proposed to increase the adhesion efficiency of targeted microbubbles and reduce the imaging time duration. Since ultrasound frequency close to lower resonance frequency of microbubbles can provide available USRF to drive microbubbles, USRF on commercialized microbubbles becomes a potential challenge on high-frequency ultrasound.
In this study, we proposed a dual-frequency (DF) excitation with a high-frequency carrier and various low-frequency envelope components to optimize the targeting efficiency of microbubbles. Results show that DF excitation with envelope frequencies (i.e., 10–30 MHz) close to the resonance frequency of submicron in-house bubbles (i.e., 9–35 MHz) resulted in targeting enhancement of 3.3–6.2 folds at the duration of 2 minutes. In addition, the high-frequency carrier of DF excitation provides a more localized microbubbles adhesion area, showing great promise to reduce the biological effect of ultrasound targeted therapy.
In the second part, we combined DF excitation with chirp reversal technique (referred to DF-chirp reversal) to selectively image the adherent microbubbles. Since DF chirp excitation can be compressed by matched filtering to suppress tissue components, the contrast-to-tissue ratio can be up to 24.8 dB in-vitro phantom experiments. Therefore, the DF-chirp reversal method has the potential to be implemented in a real-time ultrasound molecular imaging system.

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