Miniaturized Handheld Confocal Microscopy for Neurosurgery: Results in an Experimental Glioblastoma Model
Miniaturized Handheld Confocal Microscopy for Neurosurgery: Results in an Experimental Glioblastoma Model
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DOI：
10.1227/01.neu.0000365772.66324.6f
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发表时间：
2010-02-01
期刊：
影响因子：
4.8
通讯作者：
Preul, Mark C.
中科院分区：
文献类型：
--
作者：
Sankar, Tejas;Delaney, Peter M.;Preul, Mark C.
导言：光学科学和图像处理的最新发展使共焦显微镜所需的组件微型化。临床共聚焦成像应用已经出现，包括在结肠镜检查中评估结肠粘膜异型增生。方法：12只C57/BL6小鼠脑内植入10(5)个GL261胶质母细胞瘤细胞。分别于植入后第14天和第21天对6只麻醉小鼠的大脑进行手术暴露，并使用固定在立体定向框架上的手持共聚焦探头对脑表面进行成像。该探针被系统地移动到正常组织和含有肿瘤的组织区域。采用静脉注射荧光素和局部注射吖啶黄素造影剂。在探头下方的每个成像部位进行活检，并进行组织学评估。结果：手持共聚焦成像可获得与相应组织切片良好相关的脑胶质瘤浸润性小鼠脑内细胞形态和组织结构的精细图像。可复制的皮质血管构筑模式以及正常的灰质和白质被识别出来。影像能有效区分肿瘤和非肿瘤组织，包括浸润性肿瘤边缘。结论：微型化手持共聚焦成像技术可以帮助神经外科医生在手术中发现浸润性脑肿瘤的边缘。它可能有助于避免异质性胶质肿瘤活检时的抽样错误，并有可能补充常规术中冰冻切片病理。根据这些有希望的初步结果，临床试验是有必要的。
INTRODUCTION: Recent developments in optical science and image processing have miniaturized the components required for confocal microscopy. Clinical confocal imaging applications have emerged, including assessment of colonic mucosal dysplasia during colonoscopy. We present our initial experience with handheld, miniaturized confocal imaging in a murine brain tumor model.METHODS:Twelve C57/BL6 mice were implanted intracranially with 10(5) GL261 glioblastoma cells. The brains of 6 anesthetized mice each at 14 and 21 days after implantation were exposed surgically, and the brain surface was imaged using a handheld confocal probe affixed to a stereotactic frame. The probe was moved systematically over regions of normal and tumor-containing tissue. Intravenous fluorescein and topical acriflavine contrast agents were used. Biopsies were obtained at each imaging site beneath the probe and assessed histologically. Mice were killed after imaging.RESULTS: Handheld confocal imaging produced exquisite images, well-correlated with corresponding histologic sections, of cellular shape and tissue architecture in murine brain infiltrated by glial neoplasm. Reproducible patterns of cortical vasculature, as well as normal gray and white matter, were identified. Imaging effectively distinguished between tumor and nontumor tissue, including infiltrative tumor margins. Margins were easily identified by observers without prior neuropathology training after minimum experience with the technology.CONCLUSION: Miniaturized handheld confocal imaging may assist neurosurgeons in detecting infiltrative brain tumor margins during surgery. It may help to avoid sampling error during biopsy of heterogeneous glial neoplasms, with the potential to supplement conventional intraoperative frozen section pathology. Clinical trials are warranted on the basis of these promising initial results.