慣性空化現象與高強度聚焦超音波熱消融之研究

Abstract

聚焦超音波 (FUS) 和聲空化在生物醫學領域中具有重要的應用，已是最強大的非侵入性技術。高強度聚焦超音波 (HIFU) 能夠精確瞄準身體深處的組織，實現腫瘤消融和藥物傳輸等介入性治療。聲空化，即是在聲壓下，氣泡的形成和破裂。在醫療中，聲空化的超音波增強效果(包括組織破壞和標靶治療) 扮演著至關重要的作用。

在本論文中，對多頻 (雙頻和三頻) 超音波訊號作用下的黏彈性介質中的慣性空化 (氣泡破裂) 現象進行了數值研究。與傳統的單頻訊號相比，利用多頻訊號可以降低慣性空化閾值。降低慣性空化閾值對於提高基於 FUS 的治療之有效性和安全性至關重要。降低閾值可以改善組織破壞，增強目標性治療傳遞，並大幅度地降低對周圍健康組織造成損害的風險。慣性空化閾值透過不同的標準來估計：一個基於氣泡半徑擴展，另一個基於氣泡破裂速度。計算了不同初始氣泡半徑、聲音訊號模式 (單頻、雙頻或三頻)、頻率、介質參數及其各自組合的閾值壓力。結果表明，與標準單頻訊號相比，雙頻訊號採用特殊頻率組合可顯著降低慣性空化閾值。此外，三頻訊號 (也具有特定頻率) 的閾值比雙頻訊號甚至更低。大多數使慣性空化閾值最小化的頻率組合至少包含一個低頻組成 (約 0.02 MHz)。因此，為了更好地降低慣性空化閾值，最好利用多頻訊號中的低頻組成。慣性空化標準並不精確，因此每個標準提供的閾值壓力都不同。氣泡破裂速度標準給出的閾值比氣泡半徑標準給出的閾值更高。熱和機械空化效應的結果表明，與半徑標準相比，氣泡破裂速度標準顯著增加了功率沉積和應變相關的損傷面積。目前的數值研究可能對未來各種生物醫學超音波應用的發展是有用的。

此外，本論文透過數值模擬和離體實驗研究了HIFU沿著方形螺旋路徑引起的熱消融。

HIFU 已被廣泛用於透過熱消融過程對癌症腫瘤進行非侵入性治療。然而，HIFU 治療的療效仍受到治療時間過長和消融不完全的限制。本研究透過在連續掃描模式下，沿著方形螺旋路徑移動 HIFU 傳感器來研究一種更有效的消融方法。最初，透過理論模擬估計了幾個參數集，包括運動速度和螺旋線之間的間距。隨後，在豬肌肉的離體實驗中進行了驗證。結果表明，沿著方形螺旋路徑 (尺寸約為 2×2 cm^2 或 3×3 cm^2) 可以產生均勻的橫斷面損傷，但必須仔細選擇速度和間距以防止損傷稀疏。此外，研究結果顯示，沿著聚焦軸的損傷深度可達約 1.5-2 公分。根據目前的理論和實驗結果，均勻消融區域均位於聚焦前區域，聚焦和聚焦後區域的損傷並不具有那麼好的均勻性。所獲得的結果可能是有益的，也可以幫助進一步理解、研究和最佳化 HIFU 熱消融期間的掃描路徑。

Focused ultrasound (FUS) and acoustic cavitation have emerged as powerful non-invasive techniques with significant applications in biomedicine. High-intensity focused ultrasound (HIFU) is able to precisely target tissues deep within the body, enabling therapeutic interventions such as tumor ablation and drug delivery. Acoustic cavitation, the formation and collapse of gas bubbles under acoustic pressure, plays a crucial role in enhancing the effects of ultrasound in medical treatments, including tissue disruption and targeted therapy. In the present thesis, the phenomenon of inertial cavitation (bubble collapse) in viscoelastic media subjected to multi-frequency (dual- and triple-frequency) ultrasound signals was numerically investigated. Utilizing a multi-frequency signal allows for a reduction in the inertial cavitation threshold compared to traditional single-frequency signals. Reducing the inertial cavitation threshold may be crucial for enhancing the efficacy and safety of FUS-based therapies. Lowering the threshold can improve tissue disruption, enhance targeted treatment delivery, and minimize the risk of damage to surrounding healthy tissues.

The inertial cavitation threshold was estimated by using distinct criteria: one based on the bubble radius expansion and the other based on the bubble collapse speed. The threshold pressure was calculated for different initial bubble radii, acoustic signal modes (single-, dual-, or triple-frequency), frequencies, medium parameters, and their respective combinations. The obtained results demonstrate that using special frequency combinations for the dual-frequency signal significantly decreases the inertial cavitation threshold in comparison to the standard single-frequency signal. Moreover, a triple-frequency signal (also with specific frequencies) results in an even lower threshold than a dual-frequency signal. Most of the frequency combinations that minimize the inertial cavitation threshold include at least one low-frequency component (about 0.02 MHz). Therefore, for better reducing the inertial cavitation threshold, it is better to use low-frequency component in a multi-frequency signal. The inertial cavitation criteria are not precise, therefore, each criterion provides different threshold pressures. The bubble collapse speed criterion gives higher threshold values than the bubble radius criterion. Results of thermal and mechanical cavitation effects demonstrate that the bubble collapse speed criterion significantly increases power deposition and strain-related damaged area compared to the radius criterion. The current numerical study may be useful for the future development of various biomedical ultrasound applications.

Furthermore, in the present thesis, the thermal ablation induced by HIFU along square spiral pathways was studied through both numerical simulations and ex vivo experiments.

HIFU has been widely used as a non-invasive treatment for cancer tumors through the thermal ablation process. However, the efficacy of HIFU therapy remains limited by prolonged treatment times and incomplete ablation. This work investigates a more efficient ablation method by moving the HIFU transducer along square spiral pathways in continuous scanning mode. Several parameter sets, including movement speed and the spacing between spiral lines, were initially estimated through theoretical simulations and subsequently validated in ex vivo experiments on porcine muscle. The results indicate that uniform cross-sectional lesions can be generated along the square spiral pathway (with size about 2×2 cm^2 or 3×3 cm^2), although the speed and spacing must be carefully chosen to prevent sparse lesions. Additionally, the findings show that lesion depth along the focal axis can reach approximately 1.5–2 cm. According to the current theoretical and experimental results, all uniform ablated regions are located in the pre-focal area, and lesions in the focal and post-focal areas do not have such good uniformity. The obtained results may be beneficial and can help further understanding, investigation, and optimization of the scanning pathways during the HIFU thermal ablation.