Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker.
Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker.
复制标题
颅内肿瘤中的定量荧光：对ALA诱导的PPIX作为术中生物标志物的影响。
DOI：
10.3171/2011.2.jns101451
复制
发表时间：
2011-07
影响因子：
4.1
通讯作者：
Roberts DW
中科院分区：
文献类型：
--
作者：
Valdés PA;Leblond F;Kim A;Harris BT;Wilson BC;Fan X;Tosteson TD;Hartov A;Ji S;Erkmen K;Simmons NE;Paulsen KD;Roberts DW
肿瘤和正常组织之间的准确区分对于最佳肿瘤切除至关重要。在给予δ-氨基乙酰丙酸（ALA）后内源性合成的原卟啉IX（PpIX）的定性荧光已用于高级别胶质瘤（HGG）的这一目的。作者表明，可以在体内定量测量具有诊断意义但视觉上难以察觉的PpIX浓度，并用于在一系列肿瘤组织学中区分正常脑组织和肿瘤脑组织。作者研究了14例诊断为低级别胶质瘤（LGG）、HGG、脑膜瘤和转移瘤的患者，这些患者根据机构审查委员会批准的荧光引导切除方案进行治疗。该研究的主要目的是比较高灵敏度的光谱分辨定量荧光方法与传统荧光成像检测体内肿瘤组织的诊断能力。与正常脑组织相比，在所有肿瘤组中PpIX浓度的定量测量发生显着差异。PpIX浓度作为检测肿瘤组织的诊断变量的受试者工作特征（ROC）曲线分析产生了87%的分类效率（AUC = 0.95，特异性= 92%，灵敏度= 84%）与66%相比，（AUC = 0.73，特异性= 100%，灵敏度= 47%）（p < 0.0001）。在所有肿瘤的分析中，超过81%（57/70）的定量荧光测量值低于外科医生的视觉感知阈值，并被正确分类。这些发现具有临床意义，因为它们证明了ALA诱导的PpIX是HGG以外的各种颅内肿瘤的靶向生物标志物。这项研究是第一个定量测量ALA诱导的体内PpIX浓度，结果对颅内肿瘤切除术的指导具有广泛的意义。
Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.