在限制環境下產生慣性空化作用,體外及離體研究

Abstract

體外震波碎石(Extracorporeal shock wave lithotripsy, ESWL)的技術在過去幾十年來已被廣泛的使用在治療腎結石，很多證據說明震波碎石原理主要靠的是慣性空化效應(inertial cavitation)產生氣泡和氣泡爆裂(bubble collapse)的力量造成結石碎裂。近年來震波也用在治療一些軟組織發炎，像是肌腱炎之類的疾病，然而空化效應會不會發生在較緊密的組織中，而形成肌腱炎治療的機制，則因為沒有直接的證據，還無法完全明白。為了瞭解震波治療其中可能的物理機制，本研究致力於尋找震波治療的時候空化效應在組織內發生的證據，並且找出影響氣泡產生的因素。假設震波引起空化效應的反應需要一定的空間讓氣泡擴張，因此在較大的空腔中，例如較粗的血管內，比較容易產生空化效應，而在更小的空間，像是細胞間隙或是細胞內產生空化效應會比較困難。為了證實這個假設，以下設計了一系列的實驗去偵測在組織內空化效應發生的訊號，包含使用不同緻密度的組織塊的離體組織(ex vivo)實驗，和使用血管仿體去測試不同的血管大小造成的限制的體外(in vitro)實驗。實驗中發現在組織塊中要使用震波產生空化效應和組織塊本身的緻密度或是含水量有很大的關聯，在肝臟中氣泡產生的量遠比肌肉中的多，而在肌腱組織內並沒有偵測到類似氣泡產生的訊號。在血管仿體的實驗中，血管直徑大於0.7mm的仿體，不管血流流動或是血管中的液體靜止時，都可以很輕易的產生空化效應，而直徑小於0.7mm的血管仿體中，以相同的聲參數發射震波也無法有氣泡在其內產生，也就是說管徑大小的限制存在。但是當血管內流動的液體加了少量的超音波顯影劑之後，0.7mm這個閥值馬上明顯的降低，甚至在血管直徑為0.32mm的仿體中，只要有超音波顯影劑存在於血管中的流體，一次震波發射都可以明顯接收到氣泡產生後散射的訊號，可見管徑大小對產生限制空化作用的機制在有效減少空化作用起始核的量。另外，實驗中發現空化效應在血管中產生的氣泡可以明顯的提升影像的訊號雜訊比(signal-to-noise ratio)，遠比超音波顯影劑本身散射所提供的訊號加強還多。在實驗中體積濃度百分比在0.005%(v/v)的顯影劑在影像中僅僅提升2到3的灰階值，但是在此情形下只要有震波發射，就可以提升到76個灰階值，提升訊號雜訊比的程度比顯影劑好很多。一些簡單的模擬也用來進一步解釋一些氣泡的動態行為。

Shock wave has been used routinely for the treatment of urolisthesis for decades. Strong evidences suggest that cavitation bubble activity plays an important role on the stone breakage. Recently, shock wave was also shown to be effective in the treatment of certain soft tissue disorders such as tendinosis. However, whether or not cavitation occurs in tight tissue and contributes to tendon healing as well as pain relief remain unknown. In order to understand the possible physical mechanism of the shock wave therapy, we focused on searching the evidences of cavitation in tissue during the shock wave treatment, and also the determining factors of bubble generation. It was hypothesized that the shock-wave induced cavitation was constrained by the space for bubble expansion, and thus occurred more easily in vessels of larger diameters than capillaries, intercellular space and inside cells. To prove our hypothesis, a series of studies was performed to detect the presence of inertial cavitation in soft tissue blocks of various densities ex vivo and elastic tissue phantoms embedded with vessels of different size in vitro. We found that shock-wave induced bubble generation highly depended on the ‘porosity’ (equivalent to the perfusion status) of the ex vivo tissue blocks. The bubble generation in muscle was substantially less than that in liver, and was undetectable in tendon. For vessel phantoms, cavitation occurred easily in vessels with diameters greater than or equal to 0.7 mm when tap water was pumped through. However, no trace of bubble signal was found in smaller vessels under the same acoustic conditions. Size threshold existed. After adding low concentrations of contrast agent (Definity®) in the flow-through fluid, cavitation threshold dropped substantially. For a vessel of 0.32 mm in diameter, bubble and signal enhancement could be easily obtained even after a single shot of shock wave. Furthermore, the presence of cavitation-induced bubbles significantly enhanced the signal-to-noise ratio of vessels in the B-mode image, compared with the use of contrast agent alone. Concentration as low as 0.005% (v/v) could elevate the B-mode’s averaged gray level in the target area up to 76 levels, much higher than the enhancement contributed by contrast agent alone (about 2 to 3 levels in this concentration). Simulation was also performed for further understanding of the possible mechanism of medium constrain on bubble dynamics.