利用非線性振盪特性偵測超音波對比劑已被廣泛使用於超音波血流成像中。根據非線性成像的報告指出，利用分辨對比劑所產生之諧波訊號，對比劑與組織可以有效的於影像中分辨出來。而高頻超音波(>10 MHz)系統雖然可以提供更高之空間解析度於微循環血流成像中。然而，受到高頻訊號的衰減以及商用對比劑共振頻率範圍的限制，無法達到足夠的訊雜比。
在本研究中，我們提出一新式的雙頻超音波來誘發對比劑產生非線性訊號於高頻超音波系統中。此成像方式之優點在於可以達到提昇對比訊號強度以及保留影像高解析度的特性。根據本研究指出，當雙頻超音波之頻差頻率成份與對比劑共振頻率接近時，雙頻超音波訊號可以有效的誘發對比劑產生非線性振動，進而大幅提昇回波訊號的強度。而此頻差頻率成份並不受限於高頻超音波探頭頻寬，故可在高頻系統下有效率誘發小氣泡產生低頻振動。
另外在超音波對比劑擊破的研究方面，利用對比劑包覆特定物質並將其擊破於特定區域已經被證實可以達到藥物輸送的目的。因此，我們亦提出一聲學方式來評估超音波對比劑在雙頻超音波下的擊破情形，並探討雙頻超音波之橫向解析度。根據研究結果顯示，雙頻超音波相對於傳統超音波具有較佳之擊破效果以及橫向解析度。
本研究主要探討雙頻超音波於對比影像的應用，並觀察不同激發參數於對比劑非線性成像的影響。根據結果顯示，雙頻超音波影像具有高對比解析度以及高橫向解析度之特性，並可於特定聲學條件有效誘發對比劑的破裂。此方法在現有之超音波系統架構上即可實現，無須做大幅的更改，具有相當的實用性。本方法除了可以用在高頻超音波血流成像外，未來亦可應用在藥物輸送的研究中。

Detection of ultrasound contrast agents (UCAs) based on their nonlinear characteristics are popular for imaging blood perfusion. Various nonlinear imaging techniques have been reported that to distinguish UCAs from tissue by exploiting their harmonic signal is efficiently in image. For microcirculation imaging, a higher frequency system (> 10 MHz) is required to obtain high spatial resolution. However, aforementioned nonlinear techniques usually suffer from insufficient signal-to-noise ratio (SNR) for intense attenuation of high-frequency nature and the limited resonance frequency range of commercialized UCAs.
In this study, we proposed a novel approach named as dual-frequency excitation to induce nonlinear scatterings from UCAs based on high-frequency ultrasound. This proposed method provides both high lateral and contrast resolution in imaging UCAs. According to our investigations, when the difference frequency component of dual-frequency excitation is close to the resonance frequency of UCAs, the oscillation of UCAs is maximized and the echo is therefore enhanced. Note that the induced difference frequency component is beyond the frequency response of the high-frequency transducer, which excite the oscillation of UCAs more efficiency at low frequency.
Besides, it has been demonstrated that by destroying the drug-encapsulated UCAs, the drug release within specific area, thus the drug delivery is therefore achieved. Therefore, we proposed an acoustic-based method to observe the destruction of UCAs under dual-frequency excitation and discuss the lateral resolution. Results showed the dual-frequency excitation has the better destruction ability and smaller lateral resolution than the tone-burst excitation.
This thesis demonstrated the applications of dual-frequency excitation in contrast imaging and discussed the effects of insonation parameters on nonlinear contrast imaging. Results showed that the dual-frequency excitation ultrasound not only provides the high resolution in imaging, but also effectively induce the destruction of UCAs under specific insonation parameters. The proposed method is available for common ultrasound system, which is easy to implement on existed setup. In addition to the high-frequency perfusion imaging, the dual-frequency excitation is also potentially useful in drug delivery studies in the future.

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