层析光动力疗法——肿瘤靶向光动力疗法治疗胰腺导管内乳头状黏液肿瘤光参量研究  

Layered-analysis Photodynamic Therapy:Study on Optical Parameters of Tumor-targeted Photodynamic Therapy for Pancreatic Intraductal Papillary Mucinous Neoplasm

作　　者：顾瑛 谭一舟 宁浩勇 GU Ying;TAN Yizhou;NING Haoyong(Department of Laser Medicine,The First Medical Center of Chinese PLA General Hospital,Beijing 100853,China;Laser Medicine Center,Hainan Hospital of Chinese PLA General Hospital;Department of Pathology,Hainan Hospital of Chinese PLAGeneral Hospital)

机构地区：[1]中国人民解放军总医院第一医学中心激光医学科,北京市100853 [2]中国人民解放军总医院海南医院激光医学中心 [3]中国人民解放军总医院海南医院病理科

出　　处：《中国激光医学杂志》2022年第6期301-312,352-356,共17页Chinese Journal of Laser Medicine & Surgery

基　　金：海南省重大科技计划资助(ZDKJ2019012);国家自然科学基金重大项目(T2293753);海南省创新平台科研专项(YSPTZX202202);中国医学科学院医学与健康科技创新工程(2019-I2M-5-061)。

摘　　要：目的探索内镜下肿瘤靶向层析光动力疗法(photodynamic therapy,PDT)治疗胰管内肿瘤的激光参量和临床应用方案,分析影响肿瘤靶向PDT选择性治疗精度的要素,阐述从层析组织光学到层析光动力效应再到层析光动力疗法的新概念与新研究方向。方法(1)分析经内镜逆行胰胆管造影术(endoscopic retrograde cholangiopancreatography,ERCP)下PDT治疗胰腺导管内乳头状黏液肿瘤(intraductal papillary mucinous neoplasm,IPMN)文献中的治疗激光数据并计算其中缺少的治疗光强度和时间两个关键参量;(2)柱形光纤传输不同光强和波长时,对其发光表面进行室温下实时连续红外测温并绘制温度随时间变化的曲线;(3)室温下红外监测新鲜离体猪胰腺动脉经激光于血管腔内照射时血管及其周边组织温度变化并绘制温度随时间变化的曲线;(4)体外测量不同波长激光经新鲜猪胰腺动脉壁和胰腺导管的光衰减并计算组织光衰减率;(5)光镜下观察激光照射后新鲜离体猪胰腺动脉、未经处理的猪正常胰腺导管、人正常主胰管和主胰管IPMN(组织切片)的结构特点与病理变化,并分层测量组织厚度。结果(1)计算出文献中缺少的治疗激光光纤表面光强的上限值为3183 mW/cm^(2),减除10%光损耗的中间值为2865 mW/cm^(2)、减除20%光损耗的下限值为2547 mW/cm^(2),及其照射时间范围为9~71 s。(2)630 nm激光以柱形光纤表面功率密度3183 mW/cm^(2)、2865 mW/cm^(2)、2547 mW/cm^(2)发光时,光纤表面温度约在30 s到达温升的平台波动期,最高温度分别为75.4℃、69.9℃、64.9℃。630 nm、532 nm、510 nm激光以柱形光纤表面功率密度735 mW/cm^(2)发光时,温升规律同前,最高温度分别为30.4℃、32.4℃、34.6℃。630 nm、532 nm激光以柱形光纤表面功率密度200 mW/cm^(2)发光时,630 nm光纤表面无明显温升,而532 nm激光约在30 s温升到达最高点28℃。(3)630 nm激光以功率密度2547 mW/cm^(2)经胰腺Objective To explore the laser parameters and clinical application of endoscope-assisted and tumor-targeted photodynamic therapy(PDT)in the treatment of pancreatic duct tumors.The factors influencing the selectivity of tumor-targeted PDT were analyzed.New concepts and research areas from layered-analysis tissue optics to layered-analysis photodynamic effect and layered-analysis photodynamic therapy were discussed and elaborated.Methods(1)The therapeutic laser data in the literature of PDT of pancreatic intraductal papillary mucinous neoplasm(IPMN)under endoscopic retrograde cholangiopancreatography(ERCP)was studied and two missing key parameters,namely,laser intensity and time,were calculated.(2)When a cylindrical optical fiber transmitted laser of different intensities and wavelengths,continued real-time infrared thermal measurement was carried out on its luminous surface in vitro at room temperature,and temperature curves with time were drawn.(3)When a fresh porcine pancreatic arteriole was irradiated intravascularly with laser,the temperature changes of the arteriole and its surrounding tissue were monitored by a infrared thermal camera at room temperature,and the temperature curves with time were drawn.(4)The optical attenuation of different wavelength laser passing through the fresh porcine pancreatic arteriole wall and pancreatic duct was measured in vitro,and the tissue optical attenuation rate was calculated.(5)The structural characteristics and histopathological changes after the irradiation of a fresh porcine arteriole,an unprocessed normal porcine main pancreatic duct,a normal human main pancreatic duct and a pancreatic IPMN were observed under microscope,and the thickness of tissue layers was measured.Results(1)The upper limit of the surface laser intensity range of the therapeutic laser fiber,which was not reported in the literature,was calculated as 3183 mW/cm^(2),the middle value with 10%loss reduction 2865 mW/cm2,the lower limit value with 20%loss reduction 2547 mW/cm^(2),and the irradiation time

关 键 词：层析光动力疗法 层析光动力效应 层析组织光学 肿瘤靶向光动力疗法 腔内肿瘤 胰腺导管内乳头状黏液肿瘤 

分 类 号：R318.51[医药卫生—生物医学工程] R735.9[医药卫生—基础医学]