聚焦超音波燒灼之焦斑生成與溫度分佈數值模擬

Numerical simulation of lesion formation and temperature distribution in HIFU ablation

陳北亭(Ben-Ting Chen)

指導教授 ： 黃仲偉

中原大學/工學院/土木工程研究所/博士(2015年)

https://doi.org/10.6840/CYCU.2015.00088

摘要

摘要

對於不適合外科手術的病患，高強度聚焦超音波已成為一種治療原發或轉移腫瘤的替代方案。為了能準確預測聚焦超音波在組織中所引致的生化效應以及發展安全、有效的臨床治療標準，有必要性深入瞭解聚焦超音波的特性。仿體實驗與數值模擬除了可供協助超音波壓電元件原型開發與最佳化設計之外，亦可協助醫師於臨床熱治療中調整操作參數，擬定更佳的治療方案。
本研究利用異丙基丙烯醯胺（N-isopropylacrylamide，簡稱為NIPAM）與甲基雙丙烯酰胺（N,N'-methylenebisacrylamide，簡稱為MBAm）製造模擬人體組織的透明仿體，利用丙烯酸（acrylic acid，簡稱為AAc）含量的多寡來調整仿體變性的臨界溫度使之落於人體感到疼痛(42 °C)以及組織變性(52 °C)的溫度。實驗量測顯示仿體的力學、熱學與聲學性質與人體軟組織相接近，且透明仿體有助於即時監測與確認熱燒灼與熱治療過程中焦斑的生成，再透過光學影像分析的技術界定出焦斑生成的範圍與條件。同時本研究亦探討聚焦超音波燒灼仿體過程中暫態與永久氣泡產生的條件，作為後續模擬燒灼過程中空穴效應考慮的時機。
本研究亦提出整合型計算架構模擬聚焦超音波於仿體的熱燒灼，利用有限元素法求解生物熱傳方程式得到仿體溫度場的分佈，其中焦斑生成視為材料變性利用潛熱加以模擬，並提出利用等價衰減係數的方式來考慮仿體隨溫度變化的材料特性以及燒灼過程中的空穴效應，最後則以修正熱劑量的方式來協助預測焦斑生成的大小、形狀與位置。本文利用不同操作功率下的仿體燒灼實驗來驗證所提之整合型計算架構，數值實例顯示出模擬所得之溫度歷時與焦斑面積與仿體實驗相符合。
最後，本文利用超音波B-mode影像資料結合物理模型與統計模型，以非侵入式方法來推估熱治療過程中的溫度場。物理模型係計算組織溫度變化所產生的熱應變，優點為溫度解析度高；統計模型則是計算組織溫度變化所造成之超音波強度變化，優點在於溫度適用範圍廣。本文提出無因次綜合指標結合兩種模型之優點，該指標係加權計算超音波影像熱應變與強度差異，並考慮量測點位與熱源點位距離之差異來推估溫度變化。離體微波加熱實驗顯示綜合指標的溫度推估誤差在5%之內，可應用於熱治療中溫度場推估。

關鍵字

聚焦超音波 ； 異丙基丙烯醯胺仿體 ； 計算架構 ； 等校衰減係數 ； 溫度推估 ； 熱影像

並列摘要

Abstract

High-intensity focused ultrasound (HIFU) has become a potential alternative to conventional therapies for primary and metastatic tumors, especially for those patients who are not suitable candidates for surgical resection. Thorough understanding of HIFU characteristics is important both for the accurate prediction of ultrasound induced bioeffects in tissues and for the development of standards to ensure the safety and efficacy of treatments. In-vitro experiments and numerical simulations are useful for prototyping and optimizing the geometries of device designs. In addition, they also form the basis of treatment planning platforms that assist physicians in tailoring thermal therapy procedures and operating parameters.
Polymerization of N-isopropylacrylamide (NIPAM) with acrylic acid (AAc) has been adopted to fabricate reusable tissue-mimicking hydrogel phantoms designed for the real-time visualization and examination of thermal lesion formation in ablation and hyperthermia therapies. The cloud point temperature of the NIPAM-based hydrogel phantoms can be adjusted by the concentration of AAc to represent the threshold temperature of pain (42 C) or tissue damage (52 C). The mechanical, thermal and acoustic properties of the developed phantoms are similar to those of human soft tissues. The ability of the phantoms to provide visualization of thermal lesions produced by either microwave or high-intensity focused ultrasound (HIFU) ablation was examined. By processing the optical images of the phantoms at different stages of the heating process, a thermal lesion can be considered formed (i.e., threshold temperature reached) when the grayscale value reaches the half-saturation point. Additionally, energy thresholds for inducing transient or permanent bubbles in the phantoms during HIFU ablation were also identified to shed light on the onset of cavitation or material damage.
An integrated computational framework for modeling HIFU thermal ablation is proposed in this study. The temperature field was obtained by solving the bioheat transfer equation (BHTE) through the finite element method, while the lesion was considered as denatured material and modelled with the latent heat. An equivalent attenuation coefficient, which considers the temperature-dependent properties of the phantom and ultrasound diffraction due to bubbles, is proposed in the nonlinear thermal transient analysis. Moreover, a modified thermal dose formulation is also proposed to predict the lesion size, shape, and location. In-vitro thermal ablation experiments using HIFU under different electrical powers were carried out to validate this computational framework. Our numerical results demonstrated that temperature histories and lesion areas from the proposed model correlated well with those from in-vitro experiments.
Finally, we develop a novel method for both temperature estimation and thermal mapping that uses ultrasound B-mode RF data. The proposed method is a hybrid that combines elements of physical and statistical models to achieve higher precision and resolution of temperature variations and distribution. We propose a dimensionless combined index (CI) that combines the echo shift differential and signal intensity difference with a weighting factor relative to the distance from the heat source. In vitro experiments were performed, verifying that the combined index has a strong linear relationship with temperature variation and can be used to effectively estimate temperature with an average relative error of less than 5%. This algorithm provides an alternative for imaging guidance-based techniques during thermal therapy, and could easily be integrated into existing ultrasound systems.

並列關鍵字

temperature estimation ； thermal mapping ； equivalent attenuation coefficient ； computational framework ； High-intensity focused ultrasound ； NIPAM-based phantom

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