Three-dimensional visualization of protein expression in mouse brain structures using imaging mass spectrometry

Abstract

We have developed a method to visualize matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) data aligned with optically determinable tissue structures in three dimensions. Details of the methodology are exemplified using the 3-D reconstruction of myelin basic protein (MBP) in the corpus callosum of a mouse brain. In this procedure, optical images obtained from serial coronal sections are first aligned to each other to reconstruct a surface of the corpus callosum from segmented contours of the aligned images. The MALDI IMS data are then coregistered to the optical images and superimposed into the surface to create the final 3-D visualization. Correlating proteomic data with anatomical structures provides a more comprehensive understanding of healthy and pathological brain functions, and holds promise to be utilized in more complex anatomical arrangements. (J Am Soc Mass Spectrom 2005, 16, 1093-1099

Imaging of Phospholipids in Formalin Fixed Rat Brain Sections by Matrix Assisted Laser Desorption/Ionization Mass Spectrometry

“…M atrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) was introduced in 1997 [1] and has been widely presented as a powerful method for imaging large [2][3][4][5][6][7][8][9][10][11][12][13][14] and small molecules [15][16][17][18][19][20][21][22][23][24] in tissue. The technique has been applied to a diverse range of applications but there has been particular interest in evaluating opportunities in disease state profiling.…”

In situ molecular imaging of proteins in tissues using mass spectrometry

“…This finding was further corroborated by measuring both mRNA expression levels and LC-MS/MS analysis of the region. In two separate studies, investigators demonstrated 3D MALDI images of the brain, detailing the workflow and reproducibility of MALDI IMS in multiple serial tissue sections [4,5]. In addition, protein-specific 3D images of mouse brains were shown in complement with MRI 3D imaging technology [6].…”

Chapter 13 Imaging of Cells and Tissues with Mass Spectrometry

“…In addition, prior to sectioning, registration marks may be added to aid in image reconstruction. The efficacy of three-dimensional image reconstruction has been demonstrated using a series of 20 μm-thick sections from a mouse brain (Crecelius et al 2005). Three-dimensional images allow the study of detailed proteomic or pharmacodynamic information by enabling the chemical reconstruction of entire organs in a structural visualization scheme.…”