Scanning Fiber Endoscope Improves Detection of 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence at the Boundary of Infiltrative Glioma
Scanning Fiber Endoscope Improves Detection of 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence at the Boundary of Infiltrative Glioma
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DOI：
10.1016/j.wneu.2018.01.151
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发表时间：
2018-05-01
影响因子：
2
通讯作者：
Preul, Mark C.
中科院分区：
文献类型：
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作者：
Belykh, Evgenii;Miller, Eric J.;Preul, Mark C.
目的：以原卟啉IX（PpIX）作为光诊断标记物的放射性引导手术切除恶性胶质瘤正在获得接受。目前的宽视场成像技术没有足够的灵敏度来检测低浓度的PpIX。我们评估了用于检测胶质瘤中PpIX荧光的扫描纤维内窥镜（SFE），并将其与配备有荧光模块的手术显微镜（OPMI）和台式共聚焦激光扫描显微镜（CLSM）进行了比较。在植入小鼠脑中后，在侵袭性神经胶质瘤生长阶段，在体外和体内评估GL 261-Luc 2细胞中5-氨基乙酰丙酸诱导的PpIX荧光，模拟残留肿瘤。术中荧光的高和低浓度的PpIX在正常脑和肿瘤区域与SFE，OPMI，CLSM，和组织病理学进行了比较。PpIX在正常脑细胞中积累，但显著低于胶质瘤细胞。SFE对荧光脑区中积累的PpIX比OPMI更敏感（P < 0.01），并且在肿瘤与背景对比度由于光漂白而减少之前显著增加成像时间（> 6倍）。当目前的检测技术无法提供可靠的可视化时，SFE可以使5-氨基乙酰丙酸标记的胶质瘤和其他肿瘤类型的准确成像。SFE对低浓度PpIX的敏感性明显高于OPMI，这与识别恶性胶质瘤的前沿或转移细胞或治疗低级别胶质瘤有关。这种新的应用有可能使手术结果受益。
OBJECTIVE: Fluorescence-guided surgery with protoporphyrin IX (PpIX) as a photodiagnostic marker is gaining acceptance for resection of malignant gliomas. Current wide-field imaging technologies do not have sufficient sensitivity to detect low PpIX concentrations. We evaluated a scanning fiber endoscope (SFE) for detection of PpIX fluorescence in gliomas and compared it to an operating microscope (OPMI) equipped with a fluorescence module and to a benchtop confocal laser scanning microscope (CLSM).METHODS: 5-Aminolevulinic acid-induced PpIX fluorescence was assessed in GL261-Luc2 cells in vitro and in vivo after implantation in mouse brains, at an invading glioma growth stage, simulating residual tumor. Intraoperative fluorescence of high and low PpIX concentrations in normal brain and tumor regions with SFE, OPMI, CLSM, and histopathology were compared.RESULTS: SFE imaging of PpIX correlated to CLSM at the cellular level. PpIX accumulated in normal brain cells but significantly less than in glioma cells. SFE was more sensitive to accumulated PpIX in fluorescent brain areas than OPMI (P < 0.01) and dramatically increased imaging time (>6x) before tumor-to-background contrast was diminished because of photobleaching.CONCLUSIONS: SFE provides new endoscopic capabilities to view PpIX-fluorescing tumor regions at cellular resolution. SFE may allow accurate imaging of 5-aminolevulinic acid labeling of gliomas and other tumor types when current detection techniques have failed to provide reliable visualization. SFE was significantly more sensitive than OPMI to low PpIX concentrations, which is relevant to identifying the leading edge or metastasizing cells of malignant glioma or to treating low-grade gliomas. This new application has the potential to benefit surgical outcomes.