胶质瘤术中体内共焦激光内窥镜成像:我们能否检测肿瘤浸润?
Intraoperative in vivo confocal laser endomicroscopy imaging at glioma margins: can we detect tumor infiltration?
发表日期:2023 Aug 04
作者:
Yuan Xu, Andrea M Mathis, Bianca Pollo, Jürgen Schlegel, Theoni Maragkou, Kathleen Seidel, Philippe Schucht, Kris A Smith, Randall W Porter, Andreas Raabe, Andrew S Little, Nader Sanai, Dennis C Agbanyim, Nikolay L Martirosyan, Jennifer M Eschbacher, Karl Quint, Mark C Preul, Ekkehard Hewer
来源:
JOURNAL OF NEUROSURGERY
摘要:
激光共焦内窥镜(CLE)是一种经美国食品药品监督管理局批准的术中实时荧光细胞分辨率成像技术,已被证明可以在神经外科手术过程中快速活体成像脑肿瘤组织结构。成功实施术中应用的一个重要目标是在渗透性胶质瘤入侵边缘处进行活体使用。然而,CLE在胶质瘤边缘的应用尚未得到充分研究。我们从两个机构收集了匹配的CLE图像和胶质瘤边缘感兴趣区域(ROIs)的组织活检标本。所有图像由4名熟悉CLE的神经病理学家进行复审。基于病理特征,实施了一个由0到5的评分系统,用于评分每个ROI的CLE和H&E图像。根据H&E评分,所有ROI被分为低肿瘤可能性(LTP)组(分数0-2)和高肿瘤可能性(HTP)组(分数3-5)。确定了CLE和H&E评分之间关于肿瘤可能性的一致性。计算了组内相关系数(ICC)和诊断性能。共分析了56个胶质瘤边缘ROIs。评分系统在H&E图像中的评估者之间的一致性可达到优秀水平(ICC [95% CI] 0.91 [0.86-0.94]),而在CLE图像中的一致性则更为中等(ICC [95% CI] 0.69 [0.40-0.83])。LTP组(0.68 [0.40-0.83])和HTP组(0.68 [0.39-0.83])的ICC(95% CI)没有显著差异。CLE和H&E评分之间的一致性为61.6%。评分系统的敏感性和特异性值分别为79%和37%。其阳性预测值(PPV)和阴性预测值分别为65%和53%。HTP组的一致性、敏感性和PPV比LTP组更高。特异性在新诊断组中较复发组更高。CLE可能能够检测到胶质瘤边缘的肿瘤浸润。然而,目前还不可靠,特别是在预计肿瘤渗透可能性较低的情况下。提出的评分系统具有出色的内部评估者间一致性,但在使用CLE图像时,其一致性仅为中等。这些结果表明,该技术在一致可行的术中指导方面仍需进一步探索,并在肿瘤边缘情况范围内具有较高的可靠性。特定结合和/或肿瘤特异性荧光染料,CLE图像图谱和对图像解释的共识指南可能有助于提高CLE的转化效应。
Confocal laser endomicroscopy (CLE) is a US Food and Drug Administration-cleared intraoperative real-time fluorescence-based cellular resolution imaging technology that has been shown to image brain tumor histoarchitecture rapidly in vivo during neuro-oncological surgical procedures. An important goal for successful intraoperative implementation is in vivo use at the margins of infiltrating gliomas. However, CLE use at glioma margins has not been well studied.Matching in vivo CLE images and tissue biopsies acquired at glioma margin regions of interest (ROIs) were collected from 2 institutions. All images were reviewed by 4 neuropathologists experienced in CLE. A scoring system based on the pathological features was implemented to score CLE and H&E images from each ROI on a scale from 0 to 5. Based on the H&E scores, all ROIs were divided into a low tumor probability (LTP) group (scores 0-2) and a high tumor probability (HTP) group (scores 3-5). The concordance between CLE and H&E scores regarding tumor probability was determined. The intraclass correlation coefficient (ICC) and diagnostic performance were calculated.Fifty-six glioma margin ROIs were included for analysis. Interrater reliability of the scoring system was excellent when used for H&E images (ICC [95% CI] 0.91 [0.86-0.94]) and moderate when used for CLE images (ICC [95% CI] 0.69 [0.40-0.83]). The ICCs (95% CIs) of the LTP group (0.68 [0.40-0.83]) and HTP group (0.68 [0.39-0.83]) did not differ significantly. The concordance between CLE and H&E scores was 61.6%. The sensitivity and specificity values of the scoring system were 79% and 37%. The positive predictive value (PPV) and negative predictive value were 65% and 53%, respectively. Concordance, sensitivity, and PPV were greater in the HTP group than in the LTP group. Specificity was higher in the newly diagnosed group than in the recurrent group.CLE may detect tumor infiltration at glioma margins. However, it is not currently dependable, especially in scenarios where low probability of tumor infiltration is expected. The proposed scoring system has excellent intrinsic interrater reliability, but its interrater reliability is only moderate when used with CLE images. These results suggest that this technology requires further exploration as a method for consistent actionable intraoperative guidance with high dependability across the range of tumor margin scenarios. Specific-binding and/or tumor-specific fluorophores, a CLE image atlas, and a consensus guideline for image interpretation may help with the translational utility of CLE.