超音波微氣泡的偵測技術，由於其具有分辨微氣泡與周圍組織背景的能力，因此已熱門被應用於血管灌流的造影上，但以上所介紹的技術，要使發射的超音波頻率打在對比劑的共振頻率上，來達到微氣泡有效共振的需求，然而，目前多數的商用超音波對比劑其共振頻率都在2-3 MHz較低的頻率範圍，這使的高頻超音波難以進行對比造影，進而損失了良好的空間解析度，為了克服此問題，雙頻頻差激發技術於本實驗室的先前研究中被建立與提出，該技術的波形為振幅調變的形式，由兩個頻率的弦波f1與f2所組成，其可在高頻的頻帶上發射，同時產生以封包頻率(f1-f2)為頻率的低頻驅動力來激發微氣泡，基於以上先前研究的優勢，本論文主軸在針對該技術，研究與探討後續的應用與改善。
在應用上，我們藉由集中來自雙頻訊號所誘發的高階非線性能量，來提升二分之一倍頻諧波影像的CTR，研究中，我們將f2發射於兩倍共振頻率，用來有效的誘發對比劑二分之一倍頻諧波訊號，而以f1為頻率的脈波也被發射，作為額外的增強成分，以提供雙頻訊號所特有的高階非線性，在透過適當的頻率選擇後，與封包頻率相關的二、三階非線性訊號恰可疊加在f2二分之一倍頻的頻帶上，我們更進一步去調整二、三階訊號間的相位來做訊號增強的最佳化，由結果表示，藉由雙頻激發的方式，二分之一倍頻影像的CTR可以被改善，此外，CTR也會隨著發射相位而呈週期性的變化，導致CTR在最大與最小值間差達9.1 dB，更重要的是，封包成分所誘發的回波訊號看來只對對比劑具有特異性，因此本方法具有提升二分之一倍頻諧波影像之SNR與CTR的潛力。
而在雙頻激發技術的改善上，我們專注於重建其軸向解析度的不足，這是因為雙頻訊號的脈波長度需要被拉長以提供足夠的封包作用力所致，為了達到這個目標，我們提出了雙頻啾聲激發技術，該技術由兩個線性調頻的啾聲訊號所組成，使其封包成份由單頻長脈波轉為啾聲訊號的形式，以作為脈衝壓縮之用，本方法主要以與封包中心頻率與頻寬相等的匹配濾波器，來選擇性的萃取並壓縮二階的對比劑非線性訊號來成像，由結果顯示，雙頻啾聲激發確實可改善目前雙頻技術的軸向解析度，同時其訊雜比也可被提升，然而，不論是雙頻啾聲激發亦或是先前的雙頻技術，當聲壓來到800 kPa以上時，會有組織非線性訊號的生成，為了更進一步解決此問題，我們也探討兩種方法，包括四階項非線性壓縮與啾聲調頻反向於組織抑制的可行性。

Microbubbles detection techniques such as phase inversion and nonlinear harmonic methods have become popular in blood perfusion imaging due to its capability to distinguish bubbles from background tissue. The aforementioned techniques require the microbubbles to effeciently oscillate by insonation with pulse transmission near to the resonance frequency of the contrast agents. However, for most commercial ultrasound contrast agents (UCAs), they are originally designed to resonate at lower frequencies ranging from 2-3 MHz, so it makes difficult in imaging by high frequency ultrasound, thus limiting the spatial resolution of imaging. To oversome this problem, a dual-frequency difference excitation tenique has been proposed in our previos studies. The proposed dual-frequency (DF) excitation waveform is an amplitude modulated wave comprising two sinusoids (f1 and f2), it can be transmitted at high frequency band while produce low frequency driving force to excite microbubbles by resultant envelope component at frequency of (f1-f2). Based on the advantages of this technique, the thesis further investigates their potential applications.
First, we concentrate the energy of nonlinear scattering induced by DF excitation to enhance the contrast to tissue ratio (CTR) of sub-harmonic imaging. In the study, the f2 at twice of the resonance frequency of UCAs is adopted to efficiently generate sub-harmonic component, and f1 is included as an ehancing component to induce high-order nonlinearity of UCAs at sub-harmonic frequency. The second and third-order nonlinear components related to envelope component would coincide at sub-harmonic frequency if a proper set of f1 and f2 are selected. We further optimize the sub-harmonic generation by tuning the phase between second and third-order component. The results show that, with dual-frequency excitation, the sub-harmonic CTR improves as compared to conventional method. Moreover, the CTR changes periodically with the phase of dual-frequency excitation, leading to a difference up to 9.1 dB between the maximal and minimal CTR. Moreover, the echo produced from the envelope component seems to be specific for UCAs and thus the proposed method has the potentials to improve both SNR (signal-to-noise ratio) and CTR in sub-harmonic imaging.
Second, we focus on reconstructing the DF technique degraded axial resolution, because pulse length has to be enlongated to provide sufficient driving force at envelope frequency. To achieve this goal, we propose a method called as dual-frequency chirp (DF chirp) excitation which comprised two linear chirp signals, the resultant envelope component is modified from a single frequency tone bursts into the chirp form for pulse compression. This method is based on selectively extracting and compressing the second order nonlinear response by a matched filter with same center frequency and bandwidth as envelope component. The results show that DF chirp is feasible to improve the axial resolution and increase SNR of conventional DF excitation technique. However, no matter the DF chirp or DF tone bursts excitations, the second-order nonlinear response appeared at region of tissue background as acoustical pressure up to 800 kPa. To solve this problem, we further discuss the feasibilities of two methods including fourth-order nonlinear compression and chirp reversal two techniques for tissue suppression.

第一章 緒論 1
1.1. 超音波對比劑影像(Ultrasound Contrast Agents Imaging)
1.1.1. 超音波對比劑與諧波訊號
1.1.2. 二倍頻諧波影像(Second Harmonic Imaging)
1.1.3. 二分之一倍頻諧波影像(Sub-Harmonic Imaging)
1.1.4. 對比劑諧波影像的限制
1.2. 雙頻影像技術(Dual-Frequency Imaging)
1.2.1. 氣泡半徑調變影像技術(Radial Modulation Imaging)
1.2.2. 二階次聲場技術(Second Order Ultrasound Field Imaging)
1.2.3. 諧波振動聲學影像技術(Harmonic Vibro-Acoustography)
1.2.4. 雙頻頻差激發影像(Dual Frequency Difference Excitation)
1.3. 啾聲激發於對比影像(Contrast Imaging with Chirp Excitation)
1.3.1. 啾聲諧波影像(Harmonic Chirp Imaging)
1.3.2. 啾聲調頻反向影像(Chirp Reversal Imaging)
1.4. 本研究目的及論文架構
第二章 雙頻頻差激發影像技術之理論基礎
2.1. 雙頻頻差激發訊號基礎
2.2. 雙頻頻差激發訊號之聲學輻射力
2.3. 對比劑受雙頻頻差激發下非線性訊號的產生
2.3.1. 先前研究的對比劑散射頻譜
2.3.2. 對比劑非線性散射頻譜之物理機制探討
第三章 雙頻頻差激發於二分之一倍頻諧波影像之應用
3.1. 雙頻頻差激發技術於二分之一倍頻諧波影像應用之方法
3.1.1. 發射頻率選擇
3.1.2. 發射相位調整
3.2. 單氣泡模擬實驗(Single Bubble Simulation)
3.3. 單氣泡模擬結果
3.4. 亮度掃描實驗(B-mode Scanning Experiment)
3.4.1. 體外仿體的製作
3.4.2. 實驗硬體系統架構
3.4.3. 實驗方法
3.5. 亮度掃描實驗結果
3.6. 結果討論
第四章 雙頻啾聲激發影像
4.1. 雙頻啾聲激發影像技術之方法(Dual-Frequency Chirp Imaging)
4.1.1. 雙頻頻差激發訊號的軸向解析度問題
4.1.2. 雙頻啾聲激發訊號的概念基礎與設計
4.1.3. 雙頻啾聲對比劑之非線性訊號與脈衝壓縮
4.1.4. 雙頻啾聲激發訊號之參數限制
4.1.5. 雙頻啾聲激發訊號之參數選擇
4.2. 亮度掃描實驗(B-mode Scanning Experiment)
4.2.1. 體外仿體實驗架構
4.2.2. 環形探頭之波束完整性(beam pattern)
4.2.3. 實驗方法
4.3. 雙頻啾聲訊號之亮度掃描實驗結果
4.4. 結果討論
第五章 結論與未來工作
5.1. 結論
5.2. 未來工作
參考文獻
口試委員之提問與答覆

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