A new molecular multimodal imaging strategy in brain tumor surgery: Nanoparticle-dependent raman spectroscopy and multispectral optoacoustic tomography for enhancing resection of malignant gliomas.

在神经胶质瘤手术中，迄今为止已经探索了各种各样的技术，以更好地可视化肿瘤组织范围及其边缘以进行切除。目前的成像方法往往受到灵敏度、特异性和空间分辨率不足的限制。一种新的独特的双模态多光谱光声断层扫描（MSOT）和拉曼纳米粒子可以准确地帮助手术中描绘胶质瘤的边缘。拉曼光谱法是一种成熟的生物分析工具，具有几个关键优势，包括对微小结构和化学变化的出色灵敏度、显微分辨率、多路复用能力以及对自发荧光和光漂白的抵抗力。然而，这种天然存在的、未增强的拉曼效应的弱点往往限制其在体内环境中的应用。我们打算通过实现表面增强拉曼散射（Sers）纳米粒子，这大大增加了拉曼信号，以克服这一限制。拉曼的其他缺点是其有限的组织深度穿透和缺乏实时提供术中图像。我们的目标是克服这些局限性的集成光声成像能力的纳米粒子通过红移其光吸收特性的近红外（NIR）。近红外窗口中的MSOT是生物医学中新兴的分子成像技术，其允许以光谱学的准确性和超声的深度分辨率描绘内在生物标志物或外在造影剂。这应该在体内小鼠神经胶质瘤模型中进行检查：MSOT-拉曼颗粒可以在体外和活小鼠中检测到，拉曼具有至少飞摩尔灵敏度，MSOT具有皮摩尔灵敏度。将MSOT-Raman纳米粒子静脉注射到携带胶质母细胞瘤的小鼠中导致肿瘤内的积累和保留，但在周围的健康组织中没有积累。这允许通过完整的颅骨进行非侵入性肿瘤描绘。MSOT-Raman纳米颗粒在不同脑（肿瘤）细胞类型中的积累、生物分布、毒性以及其在描绘肿瘤生长程度方面的准确性的测定受到检查。拉曼和光声成像可以通过更准确地描绘脑肿瘤的范围及其边缘来指导术中肿瘤切除。我们新的双模态纳米颗粒方法有望使用这些新的成像技术实现更准确的脑肿瘤成像和切除。

In glioma surgery a wide variety of techniques have been explored to date, in an effort to better visualize the tumor tissue extent and its margins for removal. Current imaging methods are often limited by inadequate sensitivity, specificity and spatial resolution. A new and unique dual-modality Multisprectral Optoacoustic Tomography (MSOT) and Raman nanoparticle can accurately help delineate the margins of gliomas intraoperatively. Raman spectroscopy is a well-established bioanalytical tool with several key advantages, including excellent sensitivity to small structural and chemical changes, microscopic resolution, multiplexing capabilities, and resistance to both autofluorescence and photobleaching. However, the weakness of this naturally occurring, unenhanced Raman effect tends to limit its utility in the in vivo setting. We intend to overcome this limitation by implementing surface enhanced Raman scattering (SERS) nanoparticles, which increase the Raman signal dramatically. The other disadvantages of Raman are its limited tissue depths penetration and the lack of providing intraoperative images in real-time. We aim to overcome these limitations by the integration of optoacoustic imaging capabilities to the nanoparticle through red-shifting its optical absorbance properties to the near-infrared (NIR). MSOT in the NIR window is an emerging molecular imaging technology in biomedicine that allows to depict intrinsic biomarkers or extrinsic contrast agents with the accuracy of spectroscopy and the depth resolution of ultrasound. This is supposed to be examined in a mouse glioma model in vivo: The MSOT-Raman particles can be detected in both, in vitro and in living mice with at least a femtomolar sensitivity by Raman and a picomolar sensitivity by MSOT. Intravenous injection of MSOT-Raman nanoparticles into glioblastoma-bearing mice leads to accumulation and retention within the tumors, but no accumulation in the surrounding healthy tissue. This allows for noninvasive tumor delineation through the intact skull. The determination of the accumulation of MSOT-Raman nanoparticles in different brain (tumor) cell types, the biodistribution, the toxicity as well as its accuracy in depicting the extent of tumor growth are subject to examination. Raman and optoacoustic imaging may allow the guidance of intraoperative tumor resection by more accurately delineating the brain tumor extent and its margins. Our new dual-modality-nanoparticle approach holds promise for enabling more accurate brain tumor imaging and resection using these novel imaging techniques.