Development of medical devices for intraoperative localization of parathyroid glands based on fluorescence technique
- Alternative Title
- 형광 기술 기반 수술 중 부갑상선 국소화를 위한 의료기들의 개발
- Abstract
- Thyroid cancer has the 10th highest incidence globally, but is also representative of Korea. In Korea, the incidence of thyroid cancer peaked in 2012. The incidence has recently remained consistent, and the mortality of thyroid cancer remains very low. This situation means that the diagnosis and treatment of the disease are well-established. A thyroidectomy, one of the treatments for thyroid cancer, is a well-established technique, but surgeons have two challenges during this surgery. Recurrent laryngeal nerve and parathyroid glands are not easily distinguishable to the naked eye, leading to unintended damage during surgery, which is a difficult problem for surgeons. These difficulties can be overcome by developing nerve monitoring devices, and devices for parathyroid glands have been developed recently. This dissertation aims to verify a technique for localizing parathyroid glands and to verify the technology transfer from the lab to clinical practice.
The core technology for localizing parathyroid glands is the use of autofluorescence in the NIR. It was first announced in 2011, and it can be applied in two forms: imaging and sensing. In this thesis, we developed imaging and sensing systems for use during surgery. The imaging device is capable of real-time monitoring, and automatically ensures and focuses the field of view around the parathyroid gland. The sensitivity of this imaging system is 98.1%, and the accuracy is 96.4%.
Meanwhile, the developed sensing system is phase-sensitive, and can be used regardless of the presence of surgical lights. The surgeon's field of view does not need to leave the surgical field, as the results can be confirmed by the probe characteristics and sound monitoring functions. In this sensing system, the parathyroid gland intensity was 332% stronger than the thyroid, and 384%, 459%, and 286% stronger than the muscles, trachea, and fat, respectively. Therefore, we have developed a parathyroid localization device that can be used during actual thyroid/parathyroid surgery.
갑상선 암은 세계에서 10번째로 높은 발병률을 보일 뿐만 아니라 대한민국에서 특징적인 암입니다. 한국에서 갑상선 암은 2012년을 정점으로 최근에 incidence는 일관되게 유지되고 있으며, mortality는 매우 낮게 유지되고 있습니다. 이런 상황은 질병의 진단법과 치료법이 잘 확립되었음을 의미합니다. 갑상선 암의 치료법 중 하나인 갑상선절제술은 잘 확립된 술기이지만, 외과의사는 수술 중 2가지 도전 과제가 있습니다. Recurrent laryngeal nerve와 parathyroid glands는 육안으로 구별이 쉽지 않아 수술중 의도치 않은 손상이 발생하여 외과의사들에게 어려운 문제였습니다. 그 중 recurrent laryngeal nerve는 국소화 하는 의료기기가 개발되어 어려움을 극복하였고, parathyroid glands는 최근 의료기기가 개발되고 있는 중입니다. 본 학위논문은 parathyroid glands를 국소화 하는 기술을 검증하고, 임상에서 가용한 기술로 전환하는 것을 목표로 작성되었습니다.
Parathyroid glands 국소화 핵심 기술은 근적외선에서 자가형광의 이용입니다. 2011년 처음 발표되었고, 이미징과 센싱과 같이 2가지 형태로 적용이 가능합니다. 본 학위논문에서는 수술 중 사용가능한 이미징 기기와 센싱 기기를 개발하였습니다. 이미징 기기는 실시간 모니터링이 가능하고, 부갑상선 주변 시야 확보와 초점을 자동으로 맞춰줍니다. 이 영상 시스템의 감도는 98.1% 이고, 정확도는 96.4% 였습니다. 한편 개발된 센싱 시스템은 phase-sensitive 기술이 적용되어 수술등의 on/off 와 상관없이 사용 가능합니다. 또한, probe device의 특성과 소리로 결과를 확인가능해서, 외과의사의 시야가 수술필드를 벗어날 필요가 없다는 장정이 있습니다. 이 센싱 시스템은 부갑상선의 신호가 갑상선보다 332%, 근육, 기관, 그리고 지방보다 각각 384%, 459%, 286% 더 강하게 측정되었습니다. 그러므로 실제 갑상선/부갑상선 수술 중 사용가능한 부갑상선 국소화 기기를 개발하였습니다.
- Issued Date
- 2020
- Awarded Date
- 2020. 8
- Type
- Dissertation
- Publisher
- 부경대학교
- Alternative Author(s)
- Yikeun Kim
- Affiliation
- 부경대학교 대학원
- Department
- 대학원 의생명융합공학협동과정
- Advisor
- Yeh-Chan Ahn
- Table Of Contents
- 1. Introduction 1
1.1. Goal 2
1.2. Motivation 2
1.3. Specific Aims 7
1.4. Summary of Chapters 8
1.5. References 8
2. Understanding of Target Organs 11
2.1. Anatomy and Physiology of Thyroid Glands 12
2.1.1. Anatomy of Thyroid Gland 12
2.1.2. Physiology of Thyroid Gland 14
2.2. Anatomy and Physiology of Parathyroid Glands 15
2.2.1. Anatomy of Parathyroid Glands 15
2.2.2. Physiology of Parathyroid Gland 17
2.3. Disease of Thyroid and Parathyroid Glands 19
2.3.1. Thyroid Cancer and Thyroid Nodules 19
2.3.2. Hypo/Hyperthyroidism and Thyroiditis 22
2.3.3. Hypo/Hyperparathyroidism and Parathyroid Cancer 23
2.4. Thyroidectomy and Parathyroidectomy 24
2.4.1. Thyroidectomy 24
2.4.2. Parathyroidectomy 27
2.5. Diagnostic Methods Currently Used in Clinical Practice 28
2.6. References 28
3. Principles on the Methods 35
3.1. Optical Properties of the Parathyroid Gland 36
3.2. Optical Window with the Near-Infrared Region in the Tissue. 38
3.3. Fluorescence 39
3.3.1. Internal Conversion 41
3.3.2. Intersystem Crossing 42
3.3.3. Stokes Shift 42
3.3.4. Self-Absorption 43
3.4. Indocyanine Green Fluorescence 44
3.5. Autofluorescence 46
3.6. Imaging System using Fluorescence Technique 48
3.6.1. Applications of Fluorescence Imaging 50
3.6.2. Fluorescence Imaging in Thyroid/Parathyroidectomy 50
3.7. Sensing System 51
3.8. Reference 53
4. Validation of the Feasibility of Early Identification Using Near-Infrared Combined Infrared Imaging Technique 58
4.1. Abstract 59
4.2. Introduction 60
4.3. Methods 62
4.3.1. Equipment for near-infrared autofluorescence imaging 62
4.3.2. Patient selection and 3-stage guideline for parathyroid gland mapping 62
4.3.3. Analysis of data 63
4.4. Results 64
4.4.1. Identification of the parathyroid gland in each stage of mapping 64
4.4.2. Accuracy of parathyroid gland mapping 68
4.5. Discussion 71
4.6. Conclusion 74
4.7. support for this study 74
4.8. Reference 75
5. Feasibility of localizing the parathyroid gland by using a combination of visible / near-infrared optical design in low-cost equipment 78
5.1. Abstract 79
5.2. Introduction 79
5.3. Materials and Methods 81
5.3.1. Intraoperative equipment set-up for near-infrared autofluorescence imaging 81
5.3.2. Patient selection and imaging procedure 82
5.3.3. Experiment principle and image analysis 85
5.4. Results 87
5.5. Discussion 89
5.6. Conclusion 92
5.7. Funding 92
5.8. Reference 93
6. Development of an intraoperative imaging system: localization system of the parathyroid autofluorescence of the fixed DSLR form over the head 96
6.1. Abstract 97
6.2. Introduction 97
6.3. Materials and Methods 99
6.3.1. Experimental Setup 99
6.3.2. Clinical Procedure 103
6.4. Results 104
6.5. Discussion 106
6.6. Conclusions 108
6.7. Acknowledgments 109
6.8. Reference 109
7. Development of a Probe type system: phase-sensitive and optical filtering detection 112
7.1. Abstract 113
7.2. Introduction 113
7.3. Materials and Methods 115
7.3.1. PG sensor design 115
7.3.2. Phase-sensitive process 117
7.4. Results 118
7.4.1. In vitro validation 118
7.4.2. In vivo experiments 120
7.5. Discussion 123
7.6. Conclusions 125
7.7. Acknowledgments 125
7.8. Reference 126
8. Conclusions and Future Directions 130
8.1. Conclusions 131
8.2. Future Directions 132
8.3. Reference 133
감사의글 134
초록 136
- Degree
- Doctor
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- 대학원 > 의생명융합공학협동과정
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