Characterization of autofluorescence and quantitative protoporphyrin IX biomarkers for optical spectroscopy-guided glioma surgery.

Characterization of autofluorescence and quantitative protoporphyrin IX biomarkers for optical spectroscopy-guided glioma surgery.
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DOI:
10.1038/s41598-021-99228-6
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发表时间:
2021-10-08
期刊:
影响因子:
4.6
通讯作者:
Suero Molina E
Suero Molina E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Black D;Kaneko S;Walke A;König S;Stummer W;Suero Molina E

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5-氨基乙酰丙酸(5-ALA)介导的荧光不能有效描绘低级别胶质瘤(LGG)或高级别胶质瘤(HGG)的浸润性肿瘤部分。虽然光谱学提高了灵敏度和精度,但目前受自身荧光和620 nm的第二原卟啉IX (PpIX)荧光状态的限制。我们研究了自体荧光,以更好地表征目前的光谱,从而提高PpIX的定量精度和灵敏度。这项研究包括128名接受恶性神经胶质瘤手术的患者。麻醉前给予5-ALA (Gliolan),并使用高光谱装置测量荧光。结果表明,在620 ~ 634 nm范围内,所有2692个测得的光谱都包含PpIX、NADH、脂褐素和黄素。对基础光谱进行了表征,并将其用于光谱分离,与以往的工作相比,弱荧光区域的拟合误差降低了82.4% (p < 0.001),对照测量中的假阳性肿瘤鉴定减少了92.3% (p = 0.0065)。他们还降低了PpIX620的贡献,从而使平均比率减少了一半(p < 0.001)。如前所述,hgg的比率约为0,lgg的比率则在增加。此外,发现比率620/634、MIB-1/Ki-67增殖指数和PpIX峰蓝移与WHO分级、荧光可见度和PpIX贡献显著相关(p < 0.001),并讨论了这三个作为定量生物标志物的价值。
5-Aminolevulinic acid (5-ALA)-mediated fluorescence does not effectively depict low grade gliomas (LGG) or the infiltrative tumor portion of high-grade gliomas (HGG). While spectroscopy improves sensitivity and precision, this is currently limited by autofluorescence and a second protoporphyrin IX (PpIX) fluorescence state at 620 nm. We investigated the autofluorescence to better characterize the present spectra and thus increase PpIX quantification precision and sensitivity. This study included 128 patients undergoing surgery for malignant glioma. 5-ALA (Gliolan) was administered before anesthesia, and fluorescence was measured using a hyperspectral device. It was found that all 2692 measured spectra consisted of contributions from 620 to 634 nm PpIX, NADH, lipofuscin, and flavins. The basis spectra were characterized and their use in spectral unmixing led to 82.4% lower fitting error for weakly fluorescing areas (p < 0.001), and 92.3% fewer false positive tumor identifications in control measurements (p = 0.0065) compared to previous works. They also decreased the PpIX620 contribution, thus halving the mean Ratio620/634 (p < 0.001). The ratio was approximately 0 for HGGs and increasing for LGGs, as demonstrated previously. Additionally, the Ratio620/634, the MIB-1/Ki-67 proliferation index, and the PpIX peak blue-shift were found to be significantly related to WHO grade, fluorescence visibility, and PpIX contribution (p < 0.001), and the value of these three as quantitative biomarkers is discussed.
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