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

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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.