Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, Arizona 85013, USA.
J Neurosurg. 2011 Oct;115(4):740-8. doi: 10.3171/2011.6.JNS11252. Epub 2011 Jul 15.
Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5-ALA)-induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000× magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection.
Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence.
Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses.
Intraoperative confocal microscopy can visualize cellular 5-ALA-induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors' institution.
低级别胶质瘤（LGG）患者的切除范围（EOR）越大，临床预后越好，但这仍然是神经外科肿瘤医生面临的一项重大挑战。尽管 5-氨基酮戊酸（5-ALA）诱导的肿瘤荧光是一种可以提高胶质瘤 EOR 的策略，但只有胶质母细胞瘤在使用 5-ALA 后常规荧光。术中共聚焦显微镜将传统共聚焦技术应用于手持探头，可提供高达 1000 倍放大倍数的实时荧光成像。作者报告了一种联合方法，即在 LGG 显微镜下切除过程中使用术中共聚焦显微镜来可视化 5-ALA 肿瘤荧光。
在给予 5-ALA 后，新诊断为 LGG 的患者接受显微镜下切除。术中共聚焦显微镜检查在以下几点进行：1）初次遇到肿瘤；2）肿瘤切除的中点；3）假定的脑肿瘤界面。这些部位的组织病理学分析将肿瘤浸润与术中细胞肿瘤荧光相关联。
10 例连续的 WHO 分级 I 和 II 级胶质瘤患者接受了 5-ALA 和术中共聚焦显微镜下的显微镜下切除术。没有患者出现明显的宏观肿瘤荧光。然而，在每种情况下，术中共聚焦显微镜都在细胞水平上识别出肿瘤荧光，这一发现与匹配的组织学分析中的肿瘤浸润相对应。
术中共聚焦显微镜可以可视化 LGG 内和脑肿瘤界面的细胞 5-ALA 诱导的肿瘤荧光。为了评估 5-ALA 在结合神经导航治疗高级别胶质瘤和与术中共聚焦显微镜和神经导航联合治疗 LGG 方面的临床价值，作者所在机构正在进行一项 IIIa 期随机安慰剂对照试验（BALANCE）。
