Abstract
Desorption electrospray ionisation mass spectrometry (DESI-MS) can image hundreds of molecules in a 2D tissue section, making it an ideal tool for mapping tumour heterogeneity. Tumour lipid metabolism has gained increasing attention over the past decade; and here, lipid heterogeneity has been visualised in a glioblastoma xenograft tumour using 3D DESI-MS imaging. The use of an automatic slide loader automates 3D imaging for high sample-throughput. Glioblastomas are highly aggressive primary brain tumours, which display heterogeneous characteristics and are resistant to chemotherapy and radiotherapy. It is therefore important to understand biochemical contributions to their heterogeneity, which may be contributing to treatment resistance. Adjacent sections to those used for DESI-MS imaging were used for H&E staining and immunofluorescence to identify different histological regions, and areas of hypoxia. Comparing DESI-MS imaging with biological staining allowed association of different lipid species with hypoxic and viable tissue within the tumour, and hence mapping of molecularly different tumour regions in 3D space. This work highlights that lipids are playing an important role in the heterogeneity of this xenograft tumour model, and DESI-MS imaging can be used for lipid 3D imaging in an automated fashion to reveal heterogeneity, which is not apparent in H&E stains alone.
Highlights
Desorption electrospray ionisation mass spectrometry (DESI-MS) can image hundreds of molecules in a 2D tissue section, making it an ideal tool for mapping tumour heterogeneity
The revised 4th edition of the classification edited by the World Health Organisation (WHO) recognises more than 120 tumour entities with distinctive morphology, location, age distribution and biologic behaviour
Multivariate analysis (MVA) was performed on the 3D data set to reveal areas of the tumour which had different regions according to their lipid profiles (Fig. 1). 3D DESI-MS imaging was able to visualise areas of distinct lipid heterogeneity within the tumour
Summary
Desorption electrospray ionisation mass spectrometry (DESI-MS) can image hundreds of molecules in a 2D tissue section, making it an ideal tool for mapping tumour heterogeneity. It is important to understand biochemical contributions to their heterogeneity, which may be contributing to treatment resistance Adjacent sections to those used for DESI-MS imaging were used for H&E staining and immunofluorescence to identify different histological regions, and areas of hypoxia. Intratumour heterogeneity is a result of evolutionary changes that occur following dynamic remodelling of the tumour microenvironment and the effects of treatment[2,3] These genetic alterations can contribute towards resistance to t herapy[4]. Molecular imaging modalities such as positron emission tomography (PET) can contribute to the management of patients with glioma Both MRI and PET have progressed substantially in investigating the heterogeneity of glial tumours as they can image whole tumours in-vivo[13,14,15] but they may fail to detect subtle but relevant structural or functional features due to their low spatial resolution
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