Bringing Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging to the Clinics

Key points

Introduction

Mass spectrometry imaging (MSI) is an emerging set of analytical techniques that hold promise in changing pathology and tissue-based diagnostics. ¹ In its simplest sense, MSI is an analytical chemistry application in which a target is analyzed using a mass spectrometer in at least 2 spatial dimensions and, in doing so, preserves the relative spatial location of molecules during analysis. The net effect is the creation of a biochemical map or ion image, or, more precisely, hundreds to thousands of concomitant ion images, each of which corresponds to the spatial distribution of a particular ion. In clinical applications, MSI can be used to map both endogenous and exogenous small molecules, ² lipids, ³ as well as peptides and proteins, ⁴ depending on the ionization technique and mass analyzer used. Several ionization techniques have been described, including secondary ionization mass spectrometry (SIMS) and ambient electrospray ionization such as desorption electrospray ionization (DESI), although these are outside of the scope of the review and are reviewed elsewhere. ⁵ This article focuses on MSI applications that use matrix-assisted laser ionization/desorption (MALDI) as the ionization source.

Although there are many variations in sample preparation and analysis in MALDI MSI, the overall approach is generally similar. MALDI MSI begins with mounting a specimen, such as a cryosectioned tissue, onto a conductive slide or plate. A chemical matrix, commonly a small organic acid such as α-cyano-4-hydroxycinnamic acid (α-CHCA) or 2,5-dihydroxybenzoic acid (DHB), is applied to the surface either through spotting or spraying a solvent containing that matrix or by subliming the matrix onto the specimen. The matrix is then dried, the sample is moved to the source and placed under vacuum, and a region of interest is selected for analysis. Analysis is performed by firing a laser at the surface that desorbs ions from the tissue, which are then analyzed by the mass spectrometer. The most common mass spectrometers used in MALDI MSI are time of flight (TOF) mass analyzers. For certain applications, high-resolution mass spectrometers such as Fourier transform ion cyclotron resonance (FT-ICR) MS provide more robust and specific analysis. More recently, ion mobility has been added to these instruments to enhance their analytical power. Although MALDI MSI was described more than 20 years ago, ⁶ it is in the last few years that significant inroads into the translational and clinical space were made. This article provides a brief overview on clinical workflows; reviews clinical opportunities to use MALDI MSI, such as neoplastic and infectious diseases; and reviews some analytical parameters to consider when thinking about these applications.