3-D imaging mass spectrometry of protein distributions in mouse Neurofibromatosis 1 (NF1)-associated optic glioma

Abstract

Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder, in which affected individuals develop tumors of the nervous system. Children with NF1 are particularly prone to brain tumors (gliomas) involving the optic pathway that can result in impaired vision. Since tumor formation and expansion requires a cooperative tumor microenvironment, it is important to identify the cellular and acellular components associated with glioma development and growth. In this study, we used 3-D matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) to measure the distributions of multiple molecular species throughout optic nerve tissue in mice with and without glioma, and to explore their spatial relationships within the 3-D volume of the optic nerve and chiasm. 3-D IMS studies often involve extensive workflows due to the high volume of sections required to generate high quality 3-D images. Herein, we present a workflow for 3-D data acquisition and volume reconstruction using mouse optic nerve tissue. The resulting 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions.

Recent advances in mass spectrometry imaging for multiomics application in neurology

“…Three‐dimensional (3D) MALDI‐MSI is an emerging label‐free bioanalytical technique capturing the spatial distribution of hundreds of molecular compounds in 3D by providing a MALDI mass spectrum for each spatial point of a 3D sample (Anderson et al, ; Duenas, Essner, & Lee, ; Giordano et al, ; Morosi et al, ; Thiele et al, ; Xiong et al, ). The first 3D MSI has used to visualize myelin basic protein in a 3D rendered volume of the corpus callosum of a mouse brain (Crecelius et al, ).…”

Advances in cellular and sub-cellular level localization of lipids and metabolites using two- and three dimensional high-spatial resolution MALDI mass spectrometry imaging

“…Supplementary Figure S1a shows bright-field microscope images of serial cryo-sections of entire fertilized zebrafish embryo at the one-cell stage. Because of the nature and complexity of 3-dimensional imaging, sample preparation is a critical step in this study as it may be time-consuming and error-prone (Anderson et al, 2016). To diversify the chemical compounds that can be studied, Figures 4.2 and 4.3).…”

Advances in MALDI imaging mass spectrometry of proteins in cardiac tissue, including the heart valve

“…The protein image data are then combined into a volume for three dimensional viewing. Modern informatic approaches and instrumentation have improved the capabilities for performing three dimensional protein imaging [77–79]. Protein images may also be linked to other biomedical imaging modalities [80] [81].…”