Chemo-informatic strategy for imaging mass spectrometry-based hyperspectral profiling of lipid signatures in colorectal cancer

Kirill A. Veselkov*, Reza Mirnezami, Nicole Strittmatter, Robert D. Goldin, James Kinross, Abigail V.M. Speller, Tigran Abramov, Emrys A. Jones, Ara Darzi, Elaine Holmes, Jeremy K. Nicholson, Zoltan Takats

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)

Abstract

Mass spectrometry imaging (MSI) provides the opportunity to investigate tumor biology from an entirely novel biochemical perspective and could lead to the identification of a new pool of cancer biomarkers. Effective clinical translation of histology-driven MSI in systems oncology requires precise colocalization of morphological and biochemical features as well as advanced methods for data treatment and interrogation. Currently proposed MSI workflows are subject to several limitations, including nonoptimized raw data preprocessing, imprecise image coregistration, and limited pattern recognition capabilities. Here we outline a comprehensive strategy for histology-driven MSI, using desorption electrospray ionization that covers (i) optimized data preprocessing for improved information recovery; (ii) precise image coregistration; and (iii) efficient extraction of tissue-specific molecular ion signatures for enhanced biochemical distinction of different tissue types. The proposed workflow has been used to investigate region-specific lipid signatures in colorectal cancer tissue. Unique lipid patterns were observed using this approach according to tissue type, and a tissue recognition system using multivariate molecular ion patterns allowed highly accurate (>98%) identification of pixels according to morphology (cancer, healthy mucosa, smooth muscle, and microvasculature). This strategy offers unique insights into tumor microenvironmental biochemistry and should facilitate compilation of a large-scale tissue morphology-specific MSI spectral database with which to pursue next-generation, fully automated histological approaches.

Original languageEnglish
Pages (from-to)1216-1221
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number3
DOIs
Publication statusPublished - 21 Jan 2014

ASJC Scopus subject areas

  • General

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