[1]王彤 任蒙蒙 徐陆正 赵燕荣 邹晶 韩鸿宾**①袁兰**.光、磁成像法探测脑胶质瘤微环境脑组织间隙结构及脑组织间液引流的变化[J].中国微创外科杂志,2020,01(1):46-51.
　Wang Tong,Reng Mengmeng,Xu Luzheng,et al.Effect of Gliomas on Interstitial Fluid and Extracellular Space Detected by Optical and Magnetic Imaging[J].Chinese Journal of Minimally Invasive Surgery,2020,01(1):46-51.
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光、磁成像法探测脑胶质瘤微环境脑组织间隙结构及脑组织间液引流的变化()
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《中国微创外科杂志》[ISSN:1009-6604/CN:11-4526/R]

卷:
01
期数:
2020年1期
页码:
46-51
栏目:
实验研究
出版日期:
2020-03-25

文章信息/Info

Title:
Effect of Gliomas on Interstitial Fluid and Extracellular Space Detected by Optical and Magnetic Imaging
作者:
王彤 任蒙蒙 徐陆正 赵燕荣 邹晶 韩鸿宾**①袁兰**
（北京大学药学院化学生物学系北京大学医药卫生分析中心，北京100191）
Author(s):
Wang Tong;  Reng Mengmeng;  Xu Luzheng;  et al.
Department of Chemical Biology, Peking University School of Pharmaceutical Science, Beijing 100191, China
关键词:
脑胶质瘤; 组织间隙; 组织间液; 光学示踪法; 磁示踪法
Keywords:
Glioma; Extracellular space; Interstitial fluid; Tracerbased optical imaging; Tracerbased MRI
文献标志码:
A
摘要:
目的探讨脑胶质瘤微环境内组织间隙（extracellular space，ECS）的结构特征以及瘤内脑组织间液(interstitial fluid，ISF)引流的变化。方法48只SD大鼠随机分为丘脑对照组、丘脑肿瘤组、尾状核对照组、尾状核肿瘤组，每组12只，每组又分为光学示踪亚组和磁示踪亚组各6只。应用光、磁示踪法，分别以Alexa Flour 594和钆喷酸葡铵（GdDTPA）作为示踪剂，对SD大鼠的丘脑、尾状核区C6胶质瘤内ECS结构及ISF的扩散过程进行示踪分析，并与相应对照组进行比较。应用MRI检测示踪剂在脑ECS中的扩散和分布，计算获取GdDTPA在脑ECS内的有效扩散系数（DECS）、清除速率（k’）、迂曲度（λ）和半衰期（t1/2）等扩散参数。应用共聚焦显微镜对注射示踪剂2 h后的离体脑切片成像，并分析得到扩散分布的最大面积。对同一脑区对照组与肿瘤组的光、磁示踪结果进行对比分析。结果与丘脑对照组比较，丘脑肿瘤组的k’显著增加［（7.27±1.08）×10-4 mm2/s vs. （3.69±0.46）×10-4 mm2/s, t=7.474, P=0.000］，t1/2显著缩短［（21.36±2.67）min vs. （53.86±3.18）min, t=-19.165, P=0.000］，DECS显著减小［(2.27±0.22)×10-4 mm2/s vs. (3.14±0.41)×10-4 mm2/s, t=-4.536, P=0.001］，λ显著增加［(2.11±0.10)% vs. (1.06±0.01)%, t=25.201, P=0.000］。与尾状核对照组比较，尾状核肿瘤组的k’显著增加［(6.87±1.09)×10-4 mm2/s vs. (3.25±0.31)×10-4 mm2/s, t=7.867, P=0.000］，t1/2显著缩短［(23.77±7.31)min vs. (87.20±4.31)min, t=-18.309, P=0.000］，DECS显著减小［(2.38±0.79)×10-4 mm2/s vs. (3.35±0.12)×10-4 mm2/s, t=-2.986, P=0.014］，λ显著增加［(2.12±0.31)% vs. (1.73±0.03)%, t=3.067, P=0012］。结论丘脑和尾状核区胶质瘤内ISF的k’、λ显著增加，t1/2、DECS显著减少。
Abstract:
ObjectiveTo investigate the structural characteristics of extracellular space (ECS) in glioma microenvironment and the changes of intrastitial fluid (ISF) drainage with in gliomas.MethodsA total of 48 SD rats were randomly divided into the following groups: thalamus control group, thalamus glioma group, caudate nucleus control group, and caudate nucleus glioma group, with each group consisted of 12 rats. Each group was further divided into opticaltracing subgroup (n=6) and magnetictracing subgroup (n=6). By using tracerbased optical and magnetic imaging methods, Alexa Flour 594 and GdDTPA were used as tracers to monitor the diffusion process of tracers in SD rats’ ECS. Tracerbased MRI was used to visualize the diffusion processes of GdDTPA in brain ECS. The diffusion coefficient (DECS), clearance (k’), tortuosity (λ) and halflife (t1/2) were measured. Confocal laser scan microscope (CLSM) was used to imaging the brain slices after 2 h injection of Alexa Flour 594. Las X software was used to analyze the maximum area of ISF diffusion area. The results of optical and magnetic imaging were compared between the control groups and glioma groups.ResultsAs compared with the thalamus control group, the thalamus glioma group showed the following results: k’ was significantly increased ［(7.27±1.08)×10-4 mm2/s vs. (3.69±0.46)×10-4 mm2/s, t=7.474, P=0.000］, t1/2 was significantly reduced ［(21.36±2.67) min vs. (53.86±3.18) min, t=-19.165, P=0.000］, DECS was significantly reduced ［(2.27±0.22)×10-4 mm2/s vs. (3.14±0.41)×10-4 mm2/s, t=-4.536, P=0.001］, and λ was significantly increased ［(211±0.10)% vs. (1.06±0.01)%, t=25.201, P=0.000］. As compared with the caudate nucleus control group, the caudate nucleus glioma group showed the following results: k’ was increased significantly ［(6.87±1.09)×10-4 mm2/s vs. (3.25±0.31)×10-4 mm2/s, t=7.867, P=0.000］, t1/2 was significantly reduced ［(23.77±7.31) min vs. (87.20±4.31) min, t=-18309, P=0.000］, DECS was significantly reduced ［(2.38±0.79)×10-4 mm2/s vs. (3.35±0.12)×10-4 mm2/s, t=-2.986, P=0014］, and λ was significantly increased ［(2.12±0.31)% vs. (1.73±0.03)%, t=3.067, P=0.012］.ConclusionAs compared with the control group, k’ and λ of ISF in gliomas of thalamus and caudate nucleus increase significantly, and t1/2 and DECS decrease significantly.

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备注/Memo

备注/Memo:
基金项目：国家自然科学基金(91330103，91630314)；国家杰出青年科学基金（61625102）；首都科技领军人才培养工程(Z181100006318003)；北京市科技计划项目（Z181100001518004）**通讯作者，Email：yuan_lan@bjmu.edu.cn（袁兰）；hanhongbin@bjmu.edu.cn（韩鸿宾） ①（北京大学第三医院放射科北京市磁共振成像设备与技术重点实验室，北京100191）
更新日期/Last Update: 2020-04-16