二次諧振響應與微氣泡濃度之評估

Abstract

雖然微氣泡在聲學場下的震盪行為相關的研究已經有一段歷史，但仍然很少有理論闡述模擬出一群濃度不同的微氣泡在聲學場下的群體效應，在本論文中，我們將先利用修更過的Rayleigh-Plesset方程式去模擬出各種不同情況下單顆微氣泡的動態震動方程式，最後將大量此類受到散射波震盪的微氣泡訊號結合，並考慮此聲波束的驅動波形對微氣泡大小分佈及受到不同聲壓大小的各種情況，最後將與實際實驗結果進行比對。微氣泡的非線性響應-二次諧振響應及次諧振響應提供了一種很容易區分微氣泡與人體組織的特性，本論文希望利用此特性以二次諧振為主要觀測訊號輔以次諧振響應訊號做比較以建構一套超音波藥物傳輸系統為目標，探討以超音波對比劑-微脂粒(liposome)作為藥物載體時，微脂粒濃度變化與超音波回波諧振頻譜強度上最適當的操作區間，希望在此操作區間內能藉由此諧振強度直接即時的推斷出所偵測到的微脂粒數量，進而能夠對載藥量做一即時監控或預估。 文中設定對比劑本身的各項物理參數，在依實驗上的不同選擇最適當的環境參數模型、發射脈衝波形選擇。接著再依經由粒徑分析儀所測得實際的粒徑大小分佈後考慮探頭響應所造成不同的驅動聲壓去模擬整群的微氣泡在超音波場下所造成的震盪變化。並分別探討當驅動波形週期數為15、20、25情況下所能監測範圍。透過實驗結果與模擬的比對發現，可行的操作區間範圍都是發生在低濃度、低週期數時。

Although the behavior of a bubble in an acoustic field has been studied for a long time, few theoretical describe the simulation of a real population of variably sized micro bubbles in a finite beam. In this thesis, we use the modified Rayleigh-Plesset equation to simulation each single bubble’s oscillator under the different acoustic pressure, and summation all the radiation signals from large number of such bubbles. Consider the effect from the waveform beam. Finally we will compare with the experience results. The nonlinear response (second harmonic , sub harmonic) come from the micro bubbles provide an easy way to separate from bubbles and tissue. We would like to use this identity to build up an ultrasound drug deliver system. We use the liposome as the ultrasound contrast agents for the drug carrier, furthermore trying to find the best region to manipulate the variations of liposome concentration and the amplitude of received spectrum. In conclusion, we wish that we could infer the amount of liposome by the amplitude of harmonic in this area, then we could not only to monitor, but also to forecast the amount of the drug carries. We set each parameter of the contrast agents, and choose the best model、input pulse waveform for the experience environment. We measure the micro bubble’s size distribution by N4-plus coulter and consider the probe effect made different acoustic pressure. We discuss the monitor range when input cycle number 15、20、25. Through experimentation result, we know that all the feasible manipulate areas occur in lower concentrations. We glad to see it, because all the clinical application are under the lower concentration.