Differential Lipid Profiles of Normal Human Brain Matter and Gliomas by Positive and Negative Mode Desorption Electrospray Ionization - Mass Spectrometry Imaging.

Alan K Jarmusch,Clint M Alfaro,Aaron A Cohen-Gadol,Valentina Pirro,Eyas M Hattab,R Graham Cooks,Shengtao Zhou

doi:10.1371/journal.pone.0163180

Abstract

Desorption electrospray ionization—mass spectrometry (DESI-MS) imaging was used to analyze unmodified human brain tissue sections from 39 subjects sequentially in the positive and negative ionization modes. Acquisition of both MS polarities allowed more complete analysis of the human brain tumor lipidome as some phospholipids ionize preferentially in the positive and others in the negative ion mode. Normal brain parenchyma, comprised of grey matter and white matter, was differentiated from glioma using positive and negative ion mode DESI-MS lipid profiles with the aid of principal component analysis along with linear discriminant analysis. Principal component–linear discriminant analyses of the positive mode lipid profiles was able to distinguish grey matter, white matter, and glioma with an average sensitivity of 93.2% and specificity of 96.6%, while the negative mode lipid profiles had an average sensitivity of 94.1% and specificity of 97.4%. The positive and negative mode lipid profiles provided complementary information. Principal component–linear discriminant analysis of the combined positive and negative mode lipid profiles, via data fusion, resulted in approximately the same average sensitivity (94.7%) and specificity (97.6%) of the positive and negative modes when used individually. However, they complemented each other by improving the sensitivity and specificity of all classes (grey matter, white matter, and glioma) beyond 90% when used in combination. Further principal component analysis using the fused data resulted in the subgrouping of glioma into two groups associated with grey and white matter, respectively, a separation not apparent in the principal component analysis scores plots of the separate positive and negative mode data. The interrelationship of tumor cell percentage and the lipid profiles is discussed, and how such a measure could be used to measure residual tumor at surgical margins.

Highlights

Ambient ionization mass spectrometry (MS) has the potential to improve tissue diagnosis and influence outcomes in patients undergoing surgical removal of cancer
The repeatability of the acquired lipid profiles is illustrated by the similarity of the negative ion mode principal component analysis (PCA), average mass spectra, and PCA-Linear discriminant analysis (LDA) cross validation results with that of a prior study [18]
Our hypothesis was supported as the complementary chemical information obtained from the positive and negative mode analyses slightly improved PCA separation of grey matter, white matter, and glioma when used together via data fusion

Summary

Introduction

Ambient ionization mass spectrometry (MS) has the potential to improve tissue diagnosis and influence outcomes in patients undergoing surgical removal of cancer. Pathologic diagnosis of gliomas, the most common malignant brain tumor, is performed upon formalin-fixed surgical biopsies via histopathology. This cannot be done on a timescale amenable to surgical guidance. Several versions of ambient ionization MS have been tested for clinical applications They include rapid evaporative MS for in vivo analysis of liver, lung, and colorectal cancers [4], desorption electrospray ionization (DESI) for detection of MRI contrast agents within tumors [5] and for analysis of frozen tissue sections, and substrate-based ambient ionization analysis of cancerous tissues; e.g., probe electrospray ionization [6] and touch spray [7,8]

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