發展超音波功能性影像在肌腱疾病之應用

Abstract

肌腱攣縮為運動醫學中常見的傷害，發展非侵入性且高成效的治療方法為迫切需要的。一般而言，在臨床治療肌腱攣縮之主要目標為鬆弛並降低肌腱的彈性來恢復其活動力。因此，肌腱彈性係數為主要用來評估其功能性恢復和治療成效之主要參數。近年來，剪切波彈性影像已經廣被應用來定量組織彈性(楊氏係數)。在等向性的組織中，組織的楊氏係數可直接藉由量測剪切波的傳遞速度求得。然而，在肌腱此種非等向性的組織中，其楊氏係數和剪切波速度之關係仍然未知。為此，本論文中主要目標為: (1) 發展脈衝式高能超音波來主之治療方法來鬆弛攣縮的肌腱組織。(2) 探索利用剪切波彈性影像定量肌腱組織彈性之可行性用以提升診斷成效。(3) 結合剪切波彈性影像和脈衝式高能超音波來即時地觀察治療前後彈性係數的變化。在論文第一部分，我們以傳統超音波B-mode影像和分離拉伸測試法來確認脈衝式高能超音波的治療成效，結果顯示脈衝式高能超音波可以有效地降低肌腱彈性和改變超音波的斑塊訊號，且斑塊訊號變化趨勢可用來觀察脈衝式高能超音波的治療成效。在論文第二部分，為了提升診斷效率，我們研究了以剪切波彈性影像技術定量肌腱組織彈性之可行性，結果顯示由剪切波彈性影像所量測到的剪切模數和分離拉伸測試法所量測到的肌腱楊氏係數高度相關，因此，藉由定量量測肌腱的剪切模數即能直接反映其彈性的變化。此外，我們進一步探討剪切波彈性影像技術和傳統B-mode超音波影像對於診斷疾病的效率，結果顯示，正常和受損肌腱組織中，剪切模數的差異比例為29.5±7.5%，而在傳統B-mode影像中，斑塊訊號強度的差異比例只有5.6±0.6%。因此剪切波彈性影像技術與傳統超音波影像相比，對於分辨肌纖維受損的肌腱疾病，有更高的鑑別能力。最後，我們結合脈衝式高能超音波和剪切波彈性影像在治療和診斷的優勢，利用量測剪切波速度來觀察脈衝高能超音波操作在不同脈衝重複頻率、脈衝數目和脈衝作用時間對於治療肌腱攣縮之成效。實驗結果驗證，當脈衝高能超音波操作在適當的脈衝重複頻率和脈衝作用時間，能在體外和活體實驗中有效降低肌腱彈性且不產生熱破壞。總體而言，在此論文中，我們成功地建構出一個多功能的平台包含新穎的治療策略和定量診斷影像模式應用在肌腱疾病上。未來我們將致力於把目前的研究結果延伸至動物和臨床實驗。

Noninvasive and effective therapeutic strategies are highly desirable for tendon contracture, a common disease in sports medicine. In general, the purpose of contracture treatment is to loosen the tendon stiffness. Thus, the stiffness factor is a major index for evaluation of functional recovery and treatment efficacy. Recently, shear wave elasticity imaging (SWEI) has emerged as a promising technique for tissue stiffness (i.e., Young’s modulus) quantification by measuring shear wave speed (SWS). In an isotropic medium, SWS is directly related to the Young’s modulus. However, in an anisotropic medium such as tendon, the relation between the Young’s modulus and the SWS remains unclear. To this end, it is therefore the goal of this thesis to (1) develop a new treatment strategy based on pulsed high intensity focused ultrasound (pulsed-HIFU) to loosen contracture tendon, (2) explore the feasibility of using SWEI to quantitatively determine the tendon stiffness for improved diagnosis, and (3) integrate SWEI with pulsed-HIFU to monitor tendon stiffness during therapy. The results in the first part of the thesis demonstrated that pulsed-HIFU can significantly change tendon stiffness, as indicated by the change of echogenicity in ultrasound B-mode images and verified by an isolated tensile testing machine (ITT). In the second part, we showed that the shear modulus in tendon estimated by SWEI is strongly related to the Young’s modulus measured by ITT. We further pointed out that SWEI is a more superior diagnostic tool than conventional B-mode ultrasound. The difference of the shear modulus between undamaged and damaged tendon is 29.5±7.5%, while that of the B-mode speckle SNR was only 5.6±0.6%. In final part of the thesis, the treatment efficacy of pulsed-HIFU operated with various acoustic parameters such as pulse repetition frequency (PRF), pulse cycles (PC) and exposure durations (ED) was investigated by SWEI. Both ex vivo and in vivo experiments indicated that the stiffness can be reduced effectively without inducing thermal effect, when PRF and PC were optimized. In summary, this thesis successfully constructed a platform consisting of a new treatment method and a quantitative diagnosis strategy for tendon diseases. Future works will focus on the application of the proposed platform to clinical studies.