High-speed functional photoacoustic microscopy for animal and human imaging
- Abstract
- Photoacoustic microscopy is a hybrid imaging modality that non-invasively visualizes the biological structures with high resolution and high sensitivity, based on photoacoustic effect. In this technique, a pulsed laser is used to excite the absorber, thus generating the photoacoustic signal via thermal expansion phenomenon. The PA signals were collected by a high-frequency transducer to form the 3D image. Therefore, it takes advantage of high optical absorption and deep penetration imaging depth, leading to being superior to conventional imaging methods such as ultrasound imaging, magnetic resonance imaging, X-rays, and computed tomography. Recently, PAM has been rapidly developed for multiple purposes in practical applications such as neurology, dermatology, cardiology, and oncology. In this study, we focus on developing the high-speed PAM system to capture the drug response in mouse-bearing tumors and human blood vessels. A novel nanomaterial is developed as an excellent contrast agent for our developed PAM system. Moreover, we design and fabricate the advanced PAM systems integrated a slider-crank scanner of view by successfully imaging whole-body small animals (nude mice) and human subjects (fingers, palms, and feet). The results demonstrated that our proposed PAM systems are potential imaging tools for ultra-widefield scanning ranges which is an important key in preclinical and clinical researches.
- Issued Date
- 2022
- Awarded Date
- 2022. 2
- Type
- Dissertation
- Publisher
- 부경대학교
- Affiliation
- Pukyong National University, Graduate School
- Department
- 대학원 4차산업융합바이오닉스공학과
- Advisor
- 오정환
- Table Of Contents
- Chapter 1 Introduction 1
1.1. Motivation 1
1.2. Photoacoustic imaging 2
Chapter 2 Photoacoustic microscopy system for anti-EGFR antibody conjugated thiol chitosan-layered gold nano-shells 5
2.1. Introduction 5
2.2. Materials and Methods 8
2.2.1 Preparation of anti-EGFR-PTX-TCS-GNSs 8
2.2.2 Characterization 10
2.2.3 Measurement of the photothermal performance of anti-EGFR-PTX-TCS-GNSs 12
2.2.4 In vitro drug release and NIR laser-triggered release of PTX 13
2.2.5 Cell culture and in vitro cytotoxicity 14
2.2.6 In vitro hemolysis studies 14
2.2.7 In vitro cellular uptake studies 15
2.2.8 In vitro chemophotothermal therapy 16
2.2.9 Animal model 17
2.2.10 Photoacoustic imaging 17
2.2.11 In vivo fluorescence imaging and accumulation analysis 18
2.2.12 In vivo chemophotothermal therapy 18
2.2.13 Statistical analysis 20
2.3. Results and Discussion 20
2.3.1 Preparation and characterization of anti-EGFR-PTX-TCS-GNSs 20
2.3.2 Measurement of the photothermal performance of anti-EGFR-PTX-TCS-GNSs 26
2.3.3 PTX loading and NIR laser-triggered drug release 30
2.3.4 In vitro cytotoxicity and hemolysis studies 34
2.3.5 In vitro cellular uptake studies 35
2.3.6 In vitro chemophotothermal therapy 36
2.3.7 Photoacoustic imaging 44
2.3.8 In vivo fluorescence (FL) imaging and accumulation analysis 47
2.3.9 In vivo chemophotothermal therapy 50
2.4. Conclusion 55
2.5. References 56
Chapter 3 Ultra-widefield photoacoustic microscopy with a dual-channel slider-crank laser-scanning apparatus for in vivo biomedical study 67
3.1. Introduction 67
3.2. Materials and Methods 71
3.2.1 The slider-crank fast-scanning system 71
3.2.2 The configuration of the SC-2-OR-FPAM 72
3.3. Results 74
3.3.1 Structure of the slider-crank scanner 74
3.3.2 Spatial resolution, penetration depth, and SNR of the CS-OR-2-FPAM system 75
3.3.3 Ex vivo PA imaging of dragonfly wings 77
3.3.4 In vivo PA imaging of a nude mouse ear 79
3.3.5 In vivo PA imaging of a rat ear 79
3.3.6 In vivo enlarged PA imaging of a mouse sagittal 81
3.3.7 In vitro mimicking circulating tumor cells 82
3.4. Discussion 83
3.5. Conclusion 85
3.6. References 88
Chapter 4 Dual fast photoacoustic & ultrasound imaging using slider-crank scanner for small animal study 91
4.1. Introduction 91
4.2. Materials and Methods 95
4.3. Results and Discussion 97
4.3.1 P-PAUS system characterization 98
4.3.2 Ex vivo dragonfly imaging 99
4.3.3 In vivo small animal imaging 102
4.3.4 In vivo human imaging 104
4.4. Conclusion 106
4.5. Reference 107
Chapter 5 Improvement photoacoustic microscopy for evaluation of blood vessels in large animal and human using slider-crank scanner 110
5.1. Introduction 110
5.2. Materials and Methods 115
5.2.1 Slider crank scanner 115
5.2.2 Dual Channel AR-PAM System with SC Scanner 116
5.2.3 In Vivo PA Experiment 117
5.2.4 Photoacoustic Image Reconstruction 119
5.3. Results 119
5.3.1 Slider crank AR-PAM 119
5.3.2 Ex vivo experiment 122
5.3.3 Multi-layered whole-body PA Imaging of Nude Mice 124
5.3.4 In Vivo Centimeter Scale Imaging of Fingers, Palm and Foot 126
5.3.5 In Vivo Burned Skin of a Human Volunteer 130
5.4. Discussion 131
5.5. Conclusion 133
5.6. References 134
Chapter 6 Conclusions 139
6.1 Finding 139
6.2 Future directions 139
Publications 140
- Degree
- Doctor
- Appears in Collections:
- 대학원 > 4차산업융합바이오닉스공학과
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