Abstract A06: Automated, high-throughput 3D desorption electrospray ionization (DESI) mass spectrometry imaging of a xenograft model of glioblastoma

Abstract

Abstract Glioblastomas are a highly aggressive brain tumor, which are commonly resistant to chemotherapy and radiotherapy. The heterogeneity of these tumors can cause major problems for diagnosis and therapy. It is therefore important to study these local variations in glioblastoma metabolism, in order to understand tumor development and to guide treatment. Desorption electrospray ionization mass spectrometry (DESI MS) imaging is a technique that can image hundreds of molecules in a 2D tissue section in a single scan, making it an ideal tool for imaging heterogeneity in tumors. Here, 3D DESI-MS imaging has been implemented to reveal lipid heterogeneity in a whole xenograft glioblastoma. In addition, immunofluorescence staining has been used to elucidate the role of hypoxia in lipid heterogeneity. Fifteen sections were taken from a xenograft glioblastoma at 120-um increments for DESI-MS imaging. DESI-MS imaging was carried out in both negative and positive ion mode, using the spatial resolution of 120um, to allow even-sized voxels. An automatic slide loader was used to allow high-throughput imaging. Recently written software at Waters, UK was used to automatically reconstruct a 3D image from the 2D DESI-MS images. Serial sections were used for immunofluorescence staining of carbonic anhydrase-9 (a marker for hypoxia). Sections also underwent H&E staining. High-throughput 3D DESI-MS imaging has been carried out to reveal lipid heterogeneity in a xenograft glioblastoma. Here, 3D DESI-MS imaging reveals segmentation of the tumor based on local lipid expression, which correlates with the histologic mapping of normoxia, hypoxia, and necrosis. Hypoxia is a key contributor to tumor heterogeneity and, importantly, is associated with aggressive tumor development. This work highlights that lipids are playing an important role in glioblastoma heterogeneity. Furthermore, DESI-MS imaging can be used for 3D lipid imaging in an automated fashion, to reveal heterogeneity that is not apparent in H&E stains alone. Citation Format: Fiona Henderson, Emrys Jones, Joanna Denbeigh, Lidan Christie, Michael A. Batey, Emmanuelle Claude, Kaye J. Williams, Adam McMahon. Automated, high-throughput 3D desorption electrospray ionization (DESI) mass spectrometry imaging of a xenograft model of glioblastoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A06.