双模切换显微内窥镜成像系统设计及应用
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摘要
为了将荧光分子成像技术应用于临床进行手术导航、肿瘤边界识别、在体显微病理诊断等,设计了一种双模切换显微内窥镜成像系统,采用荧光素钠作为荧光分子探针,高亮度蓝光LED光源作为荧光激发光源,通过切换内窥成像探头,实现了两个模态下的成像:宽场白光内窥成像模式下进行手术导航,荧光分子成像进行病变肿瘤边界识别;显微内窥成像模式下,进行在体显微病理分析,确定肿瘤良恶性及其种类。本文研究了双模切换显微内窥镜成像系统的光学特性,搭建系统并测试了相关的性能指标,展示了该系统在小鼠肝脏多模式内窥成像下的效果。研究结果表明:宽场内窥成像可以实现组织颜色和边界特征识别,显微内镜成像系统可以实现分辨率达4.4μm的组织显微成像,能够满足在体肿瘤实时手术导航和显微病理诊断的临床需求。
Clinical studies have shown that fluorescent molecular imaging technology is extensively utilized in intraoperative navigation,tumor boundary recognition,in vivo microscopic pathology diagnosis,etc.However,identification of tumor boundaries through in vivo biopsy remains a challenging task owing to the slight discrepancy between tumor tissue and surrounding normal tissue in optical imaging.To better distinguish tumor tissue and observe histopathology in clinical examination,a dual-mode switching endomicroscopic system was proposed in this paper,which consisted of wide-field imaging for surgical navigation and microscopic imaging for performing tumor boundary recognition.The system employed sodium fluorescein as a fluorescent molecular probe and an inhouse developed blue LED with high-brightness as an excitation source.Fast switching between two modes was an advantageous design for clinical surgery to effectively determine benign and malignant tumors during in vivo microscopic pathology analysis.This paper examined the feasibility of the dual-mode imaging system for mouse liver inspection in vivo.The experimental results show that dual-mode imaging can identify tissue color and boundary features with a resolution of 4.4μm.The system can meet the clinical demands of real-time surgical navigation and microscopic pathological diagnosis of in vivo tumors.
Clinical studies have shown that fluorescent molecular imaging technology is extensively utilized in intraoperative navigation,tumor boundary recognition,in vivo microscopic pathology diagnosis,etc.However,identification of tumor boundaries through in vivo biopsy remains a challenging task owing to the slight discrepancy between tumor tissue and surrounding normal tissue in optical imaging.To better distinguish tumor tissue and observe histopathology in clinical examination,a dual-mode switching endomicroscopic system was proposed in this paper,which consisted of wide-field imaging for surgical navigation and microscopic imaging for performing tumor boundary recognition.The system employed sodium fluorescein as a fluorescent molecular probe and an inhouse developed blue LED with high-brightness as an excitation source.Fast switching between two modes was an advantageous design for clinical surgery to effectively determine benign and malignant tumors during in vivo microscopic pathology analysis.This paper examined the feasibility of the dual-mode imaging system for mouse liver inspection in vivo.The experimental results show that dual-mode imaging can identify tissue color and boundary features with a resolution of 4.4μm.The system can meet the clinical demands of real-time surgical navigation and microscopic pathological diagnosis of in vivo tumors.
引文
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[2]TORRE LA,BRAY F,SIEGEL RL,et al..Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[3]ZENG H,ZHENG R,GUO Y,et al..Cancer survival in China,2003-2005:apopulation-based study[J].Int J Cancer,2015,136(8):1921-1930.
[4]靳斌,杜刚.腹腔镜技术在肝脏手术的应用与发展[J].腹腔镜外科杂志,2016,21(9):641-643.JIN B,DU G.Therapeutic effect of laparoscopic liver resection for hepatic malignancies[J].Laparoscopic surgery journal,2016,21(9):641-643.(in Chinese)
[5]金刚.肝癌手术治疗的研究进展[J].中国民族民间医药杂志,2015,24(4):41-42.JIN G.Liver cancer surgical treatment is reviewed[J].Chinese journal of ethnomedicine and ethnopharmacy,2015,24(4):41-42.(in Chinese)
[6]陈孝平,张志伟.原发性肝癌外科治疗方法的选择[J].消化外科,2004,3(6):453-456.CHEN X P,ZHANG ZH W.Selection of surgical treatment methods for primary liver cancer[J].Chin J Heptatol,2004,3(6):453-456.(in Chinese)
[7]REX DK,CUTLER CS,LEMMEL GT,et al..Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies[J].Gastroenterology,2017,112(1):24-28.
[8]XIE X S.Biochemistry.Enzyme kinetics,past and present[J].Science,2013,342(6165):1457-1459.
[9]BOURZAC K.Medical imaging:Removing the blindfold[J].Nature,2013,504(7480):10-12.
[10]王驰,旷滨,孙建美,等.超小自聚焦光纤探头的研究进展[J].中国光学,2018,11(6):875-888.WANG CH,KUANG B,SUN J M,et al..Research progress on ultra-small self-focusing optical fiber probe[J].Chinese Optics,2018,11(6):875-888.(in Chinese)
[11]贾亚威,杨晖,李然,等.激光散斑血流成像对中医理疗功效的检测[J].光学精密工程,2017,25(6):1410-1417.JIA Y W,YANG H,LI R,et al..Measurement of physical therapy efficiency of traditional Chinese medicine by laser speckle blood flow imaging[J].Opt.Precision Eng.2017,25(6):1410-1417.(in Chinese)
[12]SAKODA M,UENO S,IINO S,et al..Anatomical laparoscopic hepatectomy for hepatocellular carcinoma using indocyanine green fluorescence imaging[J].J Laparoendosc Adv Surg Tech A,2014,24(12):878-882.
[13]KUDO H,ISHIZAWA T,TANI K,et al..Visualization of subcapsular hepatic malignancy by indocyanine-green fluorescence imaging during laparoscopic hepatectomy[J].Surg Endosc,2014,28(8)2504-2508.
[14]GUDURU A,MARTZ T G,WATERS A,et al..Oxygen saturation of retinal vessels in all stages of diabetic retinopathy and correlation to ultra-wide field fluorescein angiography[J].Invest Ophthalmol Vis Sci,2016,57(13):5278-5284.
[15]ZHANG Y L,BAI L,LI Z,et al..A lower dose of fluorescein sodium is more suitable for confocal laser endomicroscopy:a feasibility study[J].Gastrointest Endosc,2016,84(6):917-923.
[16]孙洋,樊君,胡晓云,等.荧光素钠与牛血清蛋白相互作用的荧光光谱研究及其分析应用[J].化学学报,2011,69(8):937-944.SUN Y,PAN J,HU X Y,et al..Studies on the interaction between sodium fluorescein and bovine serum albumin by fluorescence spectroscopy and its analyticalapplication[J].Acta Chimica Sinica,2011,69(8):937-944.(in Chinese)
[17]任峰,张志杰,付贝贝等.宽光谱大视场光学系统设计[J].光学精密工程,2017,25(10s):66-71.REN F,ZHANG ZH J,FU B B,et al..Design of optical system with wide spectrum and large field of view[J].Opt.Precision Eng.,2017,25(10s):66-71.(in Chinese)
[18]CLEGG RM.Fluorescence resonance energy transfer[J].Curt Opin Bioteehnol,1995,6(1):103-110.