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系統識別號 U0026-2009201811265500
論文名稱(中文) 高頻超音波彈性影像用於評估薄層組織之機械特性
論文名稱(英文) High Frequency Ultrasound Elastography for Assessing the Mechanical Properties of Thin-Layer Tissues
校院名稱 成功大學
系所名稱(中) 生物醫學工程學系
系所名稱(英) Department of BioMedical Engineering
學年度 107
學期 1
出版年 107
研究生(中文) 史卓強
研究生(英文) Cho-Chiang Shih
學號 P88031012
學位類別 博士
語文別 英文
論文頁數 135頁
口試委員 指導教授-黃執中
口試委員-王士豪
口試委員-郭立杰
召集委員-林文澧
口試委員-江惠華
口試委員-崔博翔
口試委員-葉秩光
中文關鍵字 高頻超音波  彈性影像  薄層組織機械特性  剪向波  萊姆波 
英文關鍵字 high frequency ultrasound  elastography  mechanical properties of thin-layer tissues  shear wave  Lamb wave 
學科別分類
中文摘要 由於組織機械特性的改變多伴隨著其病變的發生,因此,組織的機械特性(廣泛來說為彈性及黏性)被視為一種有效的生物標記並用於診斷多種疾病。近年來,許多研究團隊發展多種不同類型的超音波彈性影像技術用以量測組織黏彈特性。其中,以超音波聲輻射力(acoustic radiation force, ARF)彈性影像技術為基礎所發展的超音波聲輻射力脈波(acoustic radiation force impulse, ARFI)影像與剪向波彈性影像(shear wave elasticity imaging, SWEI)為目前該領域發展的主流,兩者被認為在臨床診斷上有較大的潛力。這兩種方法是利用量測因超音波聲輻射力所產生的組織位移或是組織內的剪向波傳播來對該組織進行黏彈特性的定量。然而,由於此類技術多適用於量測較大型的器官(如乳房、肝臟或是腎臟等),對於如何提高影像解析度以及使用何種波傳導模型以適用於薄層組織,自今仍然存在著很大的挑戰。
有鑑於此,本論文的目的即是希望能以超音波聲輻射力彈性影像技術為基礎,準確地量測薄層組織的機械特性。為了達成這個目標,我們提出了一個雙頻超音波的概念,利用低頻超音波激發大能量的聲輻射力,再利用高頻超音波偵測薄層組織的微小局部位移,此概念能有效補償傳統低頻超音波聲輻射力技術低空間解析度的缺點。本篇論文中,我們以多種全新設計的超音波換能器實現上述雙頻超音波的概念,應用在不同薄層組織,並驗證其未來臨床上的可行性。
首先,本研究建構了一套高解析度超音波聲輻射力影像系統,搭配使用一顆雙頻共焦換能器針對各種動脈進行掃描。我們首先使用水聽器對系統進行量測,得到不同的動脈組織(包括豬主動脈、肺動脈、冠狀度及不同血溶比的血塊)在不同能量大小的超音波聲輻射力所產生的組織位移量,找出在FDA規範下,需要多少超音波聲輻射力能量才能使動脈組織位產生足夠被偵測的位移量。並以此為根據,對具有血塊的動脈以及人造動脈硬化的動脈進行掃描,結果皆能有效地重建出相對應的動脈切面之硬度分布。
為了更進一步以血管內的方式量測動脈硬化的機械特性,我們使用了一個全新設計的雙頻血管內超音波換能器,以此結合超音波聲輻射力彈性影像與血管內超音波技術。該換能器能同時激發聲輻射力並且偵測剪向波在組織內的傳播,系統再分別以剪向波的波速和振幅進行成像。最終,對仿體和患有動脈硬化的兔頸動脈進行掃描,結果皆能提供切面上硬度的分布,並區分其差異。
為了可以測得薄層組織準確的黏彈特性,我們將所發展的雙頻超音波聲輻射力彈性影像系統與萊姆波模型整合。分別利用脈波(impulse)與諧波(harmonic)的方式激發超音波聲輻射力,並且測量其導波於薄層組織中的相速,藉由擬合測得的相速與萊姆波模型來估算組織的黏彈特性。研究量測了多種厚度搭配不同黏硬度的仿體,並且分別以傳統的群速、剪向波模型與萊姆波模型對仿體進行擬合,並且與在相同仿體下使用標準機械壓縮(mechanical test)測試的結果進行比較。結果顯示,使用萊姆波模型所擬合的黏彈特性結果最為接近標準。最後,我們也使用此系統測得豬眼角膜以及兔頸動脈的黏彈特性。
在本篇論文中,我們提出了適用於薄層組織的聲輻射力彈性影像技術。藉由多種仿體、生物組織(包括動脈血管及眼角膜),並且搭配多種全新設計的超音波換能器所進行的各項實驗,皆驗證了雙頻超音波實現在聲輻射力彈性影像技術的可行性,另外,藉由多種演算法與波模型的比較,也同時確認了適用於薄層組織的解決方案。本論文所提出的概念及其實現的技術不僅解決了傳統超音波彈性影像在空間解析度不足的缺點,同時也能為量測薄層組織黏彈特性提供準確的定性、定量結果。我們期望此架構於雙頻超音波的聲輻射力彈性影像技術能夠成為未來臨床診斷上的一項新工具。
英文摘要 The mechanical properties of soft tissue are considered effective biomarkers for the diagnosis of various diseases. Several ultrasound elastography techniques have been developed for the purpose of evaluating the tissue stiffness. Among them, acoustic-radiation-force (ARF)-based elasticity imaging, including acoustic radiation force impulse (ARFI) imaging and shear wave elasticity imaging (SWEI), has been proposed and considered as a promising technique for clinical diagnosis. Based on this technique, mechanical properties of tissue can be quantified by measuring the localized tissue displacements or shear wave speed. However, characterizing the viscoelastic properties of thin-layer tissues (thickness at level of hundreds micrometer to few millimeter) has remained challenging for many years. This is because most of these ARF-based elasticity imaging modalities were mainly developed to measure organ-level tissues (i.e., breast, liver, and kidney) and were unable to measure those thin-layer tissues which need either the high spatial resolution detection and the appropriate wave propagation model.
The thesis aims to accurately estimate the mechanical properties of thin-layer tissues by using ARF-based elasticity imaging technique. To attain the goal, a concept of dual-frequency ultrasound was proposed to excite ARF with lower ultrasound frequency and detect tissue dynamic response with higher ultrasound frequency, which compensated the trade-off between the ultrasound frequency and the intensity of ARF. The concept of dual-frequency ultrasound was realized by several newly-designed ultrasound transducers in the thesis.
To determine the intensity of ARFs required to induce sufficient displacements in vascular tissues, including porcine aorta, pulmonary artery, coronary artery and different hematocrit of blood clots, several intensities of ARF under different excitation parameter were generated using the high-resolution ARFI imaging system with a confocal dual-frequency (11 and 48 MHz) transducer and measured by a calibrated hydrophone. Those acoustic intensities consistent with the regulations specified by the US Food and Drug Administration for intravascular ultrasound (IVUS) imaging applications were determined. The stiffness distributions of arteries with blood clots and artificial arteriosclerosis were determined by the ARFI images as well.
To assess the mechanical properties of atherosclerosis, an integration of IVUS and ARF-based elasticity imaging was proposed. A dual-frequency IVUS transducer with 8.5- and 31-MHz elements was fabricated and used to simultaneously induce and monitor the shear wave propagation. The integrated system was implemented using the rotating scan to achieve cross-section information of samples. The phantom results demonstrated that the system can distinguish the regions with different stiffnesses through the wave-amplitude image and the wave-velocity image which was respectively reconstructed by measuring the peak displacement and the wave velocity of shear wave propagation. Moreover, stiffness distributions of the atherosclerotic aorta from the rabbit could be obtained from these elastographic images.
To accurately determine the viscoelasticity of thin-layer tissues, Lamb wave model and our previously developed ARF-elasticity imaging system using a 4.5 MHz ring transducer and a 40 MHz needle transducer were integrated. The phase velocity in the tissue was induced by the impulse method and harmonic method. Based on the Lamb wave model, the measured shear elasticities of thin-layer phantoms of different thicknesses were consistent with the results of the mechanical test and shear wave rheological model in bulk phantoms, and the trend of measured shear viscosities was in good agreement with the results of the shear wave rheological model and measured attenuations. By contrast, the shear elasticity of thin-layer phantoms as estimated from the group velocity did not agree with the results of mechanical tests. The shear elasticity and shear viscosity of porcine cornea and rabbit carotid artery are also reported by using both the impulse and the harmonic methods.
In the thesis, a high-resolution ARF-based elasticity imaging was proposed and implemented using several dual-frequency ultrasound transducers. With appropriate algorithms and system setups, this imaging methodology can provide the stiffness distribution or the quantified mechanical properties of the thin-layer tissues including the cornea and several kinds of the artery. All results indicate that the dual-frequency ultrasound is an efficient solution for ARF-based elasticity imaging to measure the mechanical properties of thin-layer tissues and demonstrates a promising future for improving diagnoses in multiple clinical applications.
論文目次 摘要 I
ABSTRACT III
ACKNOWLEDGMENTS VI
CONTENTS VII
LIST OF FIGURES X
LIST OF TABLES XV
NOMENCLATURE XVI
Chapter 1 Introduction 1
1.1 High-Frequency Ultrasound 1
1.2 Elasticity Imaging Techniques Based on Ultrasound 4
1.2.1 Compression Elastography 6
1.2.2 Acoustic Radiation Force Impulse (ARFI) Imaging 7
1.2.3 Shear Wave Elasticity Imaging (SWEI) 9
1.2.4 Supersonic Shear Wave Imaging (SSI) 10
1.2.5 Shear Wave Dispersion Vibrometry (SDUV) 11
1.3 Motivation and Thesis Outline 13
Chapter 2 Theoretical Background 16
2.1 Mechanical Properties of Soft Tissue 16
2.1.1 Stress-Strain Relationship 16
2.1.2 Soft Tissue Biomechanics Under Dynamic Excitation 18
2.2 Acoustic Radiation Force (ARF) 20
2.3 Shear Wave Propagation in Soft Tissue 22
2.3.1 Bulk Tissues 22
2.3.2 Thin-Layer Tissues 23
2.4 Measurement of Tissue Displacement 25
Chapter 3 Evaluating the Intensity of the Acoustic Radiation Force Impulse (ARFI) in Intravascular Ultrasound (IVUS) Imaging: Preliminary In-Vitro Results 28
3.1 Introduction 28
3.2 Materials and Methods 34
3.2.1 Experimental Setup 34
3.2.2 Intensity Measurement 37
3.2.3 Preparation of Biological Tissue Samples 39
3.2.4 One-Dimensional Measurements and 2D ARFI-IVUS Imaging 40
3.3 Results and Discussion 42
3.4 Conclusion 53
3.5 Appendix 54
Chapter 4 Development of an intravascular ultrasound elastography based on a dual-element transducer 55
4.1 Introduction 55
4.2 Materials and Methods 59
4.2.1 Dual-Frequency IVUS Transducer 59
4.2.2 Experimental Setup 60
4.2.3 Gelatin Phantom 63
4.2.4 Aorta Samples 64
4.3 Results 65
4.4 Discussion 70
4.5 Conclusion 75
Chapter 5 Quantitative assessment of thin-layer tissue viscoelastic properties using ultrasonic micro-elastography with Lamb wave model 77
5.1 Introduction 77
5.2 Materials and Methods 81
5.2.1 Theoretical Background 81
5.2.2 Experimental Setup 82
5.2.3 Post Processing 84
5.2.4 Thickness-Dependent Error 87
5.2.5 Phantom and Biological Tissue Preparation 87
5.3 Results 89
5.4 Discussion 101
5.5 Conclusion 106
Chapter 6 Conclusions and suggestions for future works 108
6.1 Conclusions 108
6.1.1 Evaluating the Intensity of the Acoustic Radiation Force Impulse (ARFI) in Intravascular Ultrasound (IVUS) Imaging: Preliminary In-Vitro Results 108
6.1.2 Development of an Intravascular Ultrasound Elastography Based on a Dual-Element Transducer 109
6.1.3 Quantitative Assessment of Thin-Layer Tissue Viscoelastic Properties Using Ultrasonic Micro-Elastography with Lamb Wave Model 110
6.2 Suggestions for Future works 111
References 114
Publication List 133
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