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Time-of-Flight Secondary Ion Mass Spectrometry Based Molecular Histology of Human Spinal Cord Tissue and Motor Neurons

Journal article
Authors Jörg Hanrieder
Per Malmberg
Olle R Lindberg
John S. Fletcher
Andrew G Ewing
Published in Analytical Chemistry
Volume 85
Issue 18
Pages 8741–8748
ISSN 0003-2700
Publication year 2013
Published at Institute of Neuroscience and Physiology
Department of Chemistry and Molecular Biology
Pages 8741–8748
Language en
Links dx.doi.org/10.1021/ac401830m
Subject categories Analytical Chemistry

Abstract

Secondary ion mass spectrometry is a powerful method for imaging biological samples with high spatial resolution. Whole section time-of-flight-secondary ion mass spectrometry (TOF-SIMS) scans and multivariate data analysis have been performed on the human spinal cord in order to delineate anatomical regions of interest based on their chemical distribution pattern. TOF-SIMS analysis of thoracic spinal cord sections was performed at 5 μm resolution within 2 h. Multivariate image analysis by means of principal component analysis and maximum auto correlation factor analysis resulted in detection of more than 400 m/z peaks that were found to be significantly changed. Here, the results show characteristic biochemical distributions that are well in line with major histological regions, including gray and white matter. As an approach for iterative segmentation, we further evaluated previously outlined regions of interest as identified by multivariate image analysis. Here, further discrimination of the gray matter into ventral, lateral, and dorsal neuroanatomical regions was observed. TOF-SIMS imaging has been carried out at submicrometer resolution obtaining localization and characterization of spinal motor neurons based on their chemical fingerprint, including neurotransmitter precursors that serve as molecular indicators for motor neuron integrity. Thus, TOF-SIMS can be used as an approach for chemical histology and pathology. TOF-SIMS holds immense potential for investigating the subcellular mechanisms underlying spinal cord related diseases including chronic pain and amyotrophic lateral sclerosis.

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