Dual-Modality Surface-Enhanced Resonance Raman Scattering and Multispectral Optoacoustic Tomography Nanoparticle Approach for Brain Tumor Delineation.
Dual-Modality Surface-Enhanced Resonance Raman Scattering and Multispectral Optoacoustic Tomography Nanoparticle Approach for Brain Tumor Delineation.
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DOI：
10.1002/smll.201800740
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Kircher MF
中科院分区：
文献类型：
--
作者：
Neuschmelting V;Harmsen S;Beziere N;Lockau H;Hsu HT;Huang R;Razansky D;Ntziachristos V;Kircher MF
术中难以观察胶质瘤边缘仍然是实现肿瘤全切除的主要问题，因此，胶质母细胞瘤（GBM）患者的临床结局更好。在这里，我们研究了一种新的组合光学+光声成像方法用于术中脑肿瘤勾画的潜力。我们设计了一种策略，使用我们新开发的金纳米星合成方法，拉曼报告化学，和硅化方法，以产生双模态造影剂的组合表面增强共振拉曼散射（SERRS）和多光谱光声断层扫描（MSOT）成像。在携带Nestin-tv-a; Ink 4a/Arf-/-;Ptenfl/fl小鼠的脑肿瘤中静脉内注射SERRS-MSOT-nanostars后，在体内进行连续的横截面MSOT成像，然后进行离体拉曼成像以分析信号一致性。MSOT能够准确地描绘GBM高达几毫米的深度三维高特异性。发现MSOT信号与SERRS图像良好相关。由于SERRS能够实现独特灵敏的高分辨率表面检测，因此它可以代表MSOT的理想互补成像模式，从而实现3D实时深层组织成像。本文报道的这种双模态SERRS-MSOT-nanostar造影剂显示能够在临床相关的小鼠GBM模型中通过拉曼和MSOT成像高精度描绘浸润GBM的程度，并且可以为改善脑肿瘤的图像引导切除铺平新的道路。
Difficulty in visualizing glioma margins intraoperatively remains a major issue in the achievement of gross total tumor resection and, thus, better clinical outcome of glioblastoma (GBM) patients. Here we investigated the potential of a new combined optical + optoacoustic imaging method for intraoperative brain tumor delineation. We devised a strategy using our newly developed gold nanostar synthesis method, Raman reporter chemistry, and silication method to produce dual-modality contrast agents for combined surface-enhanced resonance Raman scattering (SERRS)- and multispectral optoacoustic tomography (MSOT) imaging. Following intravenously injection of the SERRS-MSOT-nanostars in brain tumor bearing Nestin-tv-a;Ink4a/Arf−/−;Ptenfl/fl mice, sequential cross-sectional MSOT imaging was performed in vivo and followed by ex vivo Raman imaging for analysis of signal congruency. MSOT was able to accurately depict GBMs up to a depth of several millimeters three-dimensionally with high specificity. The MSOT signal was found to correlate well with the SERRS images. Because SERRS enables uniquely sensitive high resolution surface detection, it could represent an ideal complementary imaging modality to MSOT, which enables real-time, deep tissue imaging in 3D. This dual-modality SERRS-MSOT-nanostar contrast agent reported here was shown to enable high precision depiction of the extent of infiltrating GBMs by Raman- and MSOT imaging in a clinically relevant murine GBM model and could pave new ways for improved image-guided resection of brain tumors.
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