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Intravascular Dual-Modal OCT-NIRF Structural-Molecular Imaging Combined with Indocyanine Green (ICG) for the Assessment of Coronary Stent-associated Inflammationㅡ

박동하는 관상 동맥 혈관 내에서 광단층-근적외선형광 융합 분자 이미징과 인도시아닌 그린을 이용한 스텐트 염증의 평가

  • 김선원 (Kim, Sun Won, 대학원 의학과 내과학전공)

초록/요약

Backgrounds: Despite the importance of inflammation in the pathogenesis of drug-eluting stent (DES)-related complications, there has been a lack of clinical imaging that can visualize inflammation arising on the periphery of small metallic scaffold. The purpose of this study was to examine whether intracoronary optical coherence tomography (OCT)-near infrared fluorescence (NIRF) imaging combined with indocyanine green (ICG) can assess DES-associated inflammation in vivo. Methods and results: Fully-integrated OCT-NIRF imaging system facilitating real-time simultaneous assessment of microstructural and biological information was constructed. After administration of saline or ICG (2.0 mg/kg), a Food and Drug Administration-approved NIRF enhancer, rapid coronary imaging (20 mm/sec pullback speed) was performed in DES-implanted Yorkshire pigs (n = 7). At day 14, strong NIRF activity was identified in DES-implanted segment while only minimal background NIRF in neighboring unstented artery. On synchronized OCT-NIRF images, this robust NIRF signals were mostly confined to peri-strut area and quantitative NIRF analysis demonstrated significant difference of stent target-to-background ratio between day 1 vs. day 14 (day 1 vs. day 14: mean sTBR: 1.04 ± 0.18 vs. 2.82 ± 0.79, p = 0.0156; peak sTBR: 1.99 ± 0.45 vs. 6.44 ± 1.57, p = 0.0156). There was no detectable signal in saline-injected control (ICG vs. saline: 6.44 ± 1.57 vs. 1.80 ± 0.13, p = 0.0006). Fluorescence reflectance imaging corroborated finding in vivo, demonstrating a significant correlation of NIRFs between in vivo and ex vivo imagings (r = 0.88, p < 0.0001). Confocal laser scanning microscopy (CLSM) of resected coronary artery clearly showed strong peri-strut NIRF with DES struts in situ and correlative CLSM-immunohistochemistry confirmed that this NIRF-enhancing peri-strut neointima was densely infiltrated by macrophages. Conclusions: OCT-NIRF imaging with clinically-applicable ICG demonstrated the capability to assess DES-associated arterial inflammation in a beating swine heart. The current dual-modal imaging strategy could be relevant for clinical intracoronary evaluation of individual stent and will help to clarify the role of inflammation in the course of arterial healing after stent placement.

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목차

I. 요약
II. 서론
1. 연구 배경과 목적
III. 연구 방법
1. 동물 모델
2. 광단층-근적외선 융합 분자 이미징
3. 근적외선 이미징 물질: 인도시아닌 그린
4. 생체 내 영상 실험
5. 근적외선 형광 신호 정량화 분석 방법
6. 생체 외 영상 실험: 형광 반사 이미징, 공초점 레이져 현미경
7. 조직학적 검증: 형광 현미경과 면역 염색 분석
8. 통계 분석 방법
IV. 연구 결과
1. 박동하는 관상동맥 내에서 광단층-근적외선 융합 분자 이미징
2. 생체 외 이미징을 통한 검증
3. 생체 내 이미징의 재현도 분석
4. 인도시아닌 그린과 대식구의 결합 검증을 위한 실험관 실험
V. 고찰
1. 연구 결과 요약
2. 박동 혈관 내 이미징을 위한 본 영상 기법의 우월성
3. 스텐트 염증 이미징의 중요성 및 스텐트 생착 과정에 비추어 본 연구의 의미
4. 광당층-근적외선 염증 이미징의 장점과 의미
5. 본 연구의 한계
VI. 결론
VII. 그림 설명문
VIII. 참고 문헌
IX. 감사의 말, 전재 승인서

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