自 20 世紀初以來，光學技術已被大量用於生物醫學領域。然而光在生物組織中的穿透性被蛋白質、脂質或組織結構引起的強散射嚴重限制，在臨床應用中的發展也因此受限。為了克服基本物理限制，本研究提出了超音波光學特性調製方法來增強光在散射介質中的能量傳遞。由於超音波的無創、可控和定位特性，高強度聚焦超音波（海扶）誘導的熱效應和機械效應被分別用於測試其作為光導的潛力。在第一章中，首先回顧了過去用於提高生物組織光穿透的策略。在第二章中，超音波在散射仿體中產生加熱通道，以改進測試光在散射環境中的傳輸。結果表明，由於熱效應導致散射仿體中的散射係數降低，光通量因此增加了 3%。在第三章中，超音波被用於在強散射仿體中產生微氣泡，以提供低散射通道來增加光傳遞效率。結果表明，在聚四氟乙烯納米粒子（PTFE NPs）的幫助下，可以使用相對較低能量的超音波來達成微氣泡的生成並獲得6.2%的光通量增加。綜上所述，本研究建立了兩個實時、無創、可控、可定位、可回復、並具有生物安全性的超音波光導系統來解決組織仿體中的散射問題。此系統在模擬和實驗部分都呈現出正面的結果。因此這些方法很有機會能與其他光學技術例如雙光子顯微成像系統、高分辨率光學顯微圖像或光熱療法結合，以實現改善光穿透深度的效果。

Optical technologies have been used in the biomedical field since the early 20 century. However, the strong scattering due to the protein, lipid, or tissue structure severely limits the light penetration in biological tissues and restricts its development in clinical applications. In order to overcome this physical constraint, the ultrasonic optical properties modulation method was proposed to enhance the energy delivery of the light in the scattering medium. Due to the noninvasive, controllable, and localization features of ultrasound, thermal and mechanical effects induced by high-intensity focused ultrasound (HIFU) were selected to test their potential as light-guiding methods, respectively. In chapter 1, the previous strategies to improve the light penetration in the biological tissues were firstly reviewed. In chapter 2, the ultrasound-induced heating tunnel was generated in the scattering phantom to test the improvement of the light delivery. The results demonstrate a 3% fluence increase due to the thermal effect induced scattering coefficient reduction in the scattering phantom. In chapter 3, ultrasound-induced microbubbles were generated in the strong scattering phantom to provide a low scattering tunnel to increase the light propagation. The results suggest that with the assistance of the polytetrafluoroethylene nanoparticles (PTFE NPs), relatively low energy ultrasound energy can be used to achieve microbubble generation and obtain a 6.2% increase of fluence. In summary, two real-time, noninvasive, and controllable, localization, revisable, and biosafety ultrasonic light guide systems were established to solve the scattering issue in the tissue mimic phantom. Both simulation and experiment present positive results as a light guide system. As a result, these methods have the potential to combine with other optical technologies such as two-photon microscopic imaging systems, high-resolution optical microscopy images, or photothermal therapy to improve the light penetration in their applications.

Context
List of Figures 1
List of Tables 4
Chapter1 5
Introduction 5
1.1 The application of the light in the biomedical field 5
1.2 Light delivery in biological tissue 6
1.3 The strategy to improve the light penetration in the biological tissues 8
1.3.1 Wavefront shaping technique 8
1.3.2 Optical properties modulation 9
1.3.3 Ultrasonic light guide system 10
1.4 The aim of this dissertation 10
1.4.1 Ultrasound induced thermal effects 12
1.4.2 Ultrasound induced mechanical effects 12
Chapter2 14
Improvement of light penetration in biological tissue using an ultrasound-induced heating tunnel 14
2.1 Introduction 14
2.2 Materials and methods 15
2.2.1 Optical scattering coefficients modulation due to the thermal effect 15
2.2.2 Acoustic parameter measurement 16
2.2.3 Monte Carlo simulation 17
2.2.4 Intralipid phantom fabrication 21
2.2.5 Inertial cavitation detection 22
2.2.6 Laser fluence measurement 24
2.2.7 Photoacoustic experiments 25
2.3 Results 27
2.3.1 Acoustic parameter measurement 27
2.3.2 Monte Carlo simulation results 28
2.3.3 Inertial cavitation detection during heating 29
2.3.4 Fluence enhancement by HIFU heating tunnel 30
2.3.5 Photoacoustic signal improvement by HIFU heating tunnel 31
2.4 Discussion 32
Chapter3 34
Ultrasound-guided system for light focusing using microbubbles generated from polytetrafluoroethylene nanoparticles 34
3.1 Introduction 34
3.2 Materials and methods 35
3.2.1 Monte Carlo simulation setup 35
3.2.2 The PTFE-intralipid solution fabrication 37
3.2.3 Inertial cavitation dose measurement 39
3.2.4 High-speed camera image 40
3.2.5 Light fluence measurement 41
3.3 Results 42
3.3.1 Monte Carlo simulation results 42
3.3.2 Inertial cavitation dose for bubble generation 44
3.3.3 High-speed image of the microbubble 45
3.3.4 Light fluence increased by μm size bubbles 45
3.4 Discussion 47
Chapter4 49
Discussion 49
Chapter5 50
Conclusions and Future Work 50
References 51
List of Publications 60

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