A vision for better health: mass spectrometry imaging for clinical diagnostics

Abstract

Background: Mass spectrometry imaging (MSI) is a powerful tool that grants the ability to investigate a broad mass range of molecules from small molecules to large proteins by creating detailed distribution maps of selected compounds. Its usefulness in biomarker discovery towards clinical applications has obtained success by correlating the molecular expression of tissues acquired from MSI with well-established histology.

Results: To date, MSI has demonstrated its versatility in clinical applications, such as biomarker diagnostics of different diseases, prognostics of disease severities and metabolic response to drug treatment, etc. These studies have provided significant insight in clinical studies over the years and current technical advances are further facilitating the improvement of this field. Although the underlying concept is simple, factors such as choice of ionization method, sample preparation, instrumentation and data analysis must be taken into account for successful applications of MSI. Herein, we briefly reviewed these key elements yet focused on the clinical applications of MSI that cannot be addressed by other means.

Conclusions: Challenges and future perspectives in this field are also discussed to conclude that the ever-growing applications with continuous development of this powerful analytical tool will lead to a better understanding of the biology of diseases and improvements in clinical diagnostics.

Figure 1

A schematic representation of the clinical applications of MSI. MSI mass spectra arising from the diseased regions are recorded, and the molecular MS images are reconstructed. The molecules like lipids or proteins that differentiate the diseased regions from the normal ones are potential biomarkers of the disease. Moreover, the metabolites that changed corresponding to drug treatment are also investigated based on this workflow.

Figure 2

DHA-containing PCs exhibited impact site-specific irreversible reductions from 1 day to 8 weeks post-SCI. The MSI results for DHA-containing PCs, i.e.: PC(diacyl-16:0/22:6) and PC (diacyl-18:0/22:6), are detailed. In particular, the 24 ion images for each DHA-PC from sections of normal (sham-operated) and SCI-treated samples at five different time points are shown. The distribution of DHA-PCs was unaltered at 12 h post-SCI in comparison with the control. The primary reduction was observed around the central canal and gray commissure region to a severe extent at 1 d post-SCI, whereas the decreases at the anterior and posterior horns were moderate (arrowheads). However, at 1 week post-SCI, DHA-PCs were also lost from these tissue regions, and these reductions evolved at later time points and the DHA-PCs had almost disappeared by 8 weeks post-SCI [103]. Reprinted with permission from Hanada M, Sugiura Y, Shinjo R, et al. Spatiotemporal alteration of phospholipids and prostaglandins in a rat model of spinal cord injury. Anal Bioanal Chem 2012; 403:1873-1884.

Figure 3

(a) Large area image of the hydrogel implant under the renal capsule of a rat, 15 days after implantation. Various localizations are indicated, based on PCA+VARIMAX results (see spectra in (b)) and in the overlay with an optical microscope image. The presence of lipids inside the polymer area shows cellular infiltration in the drug delivery carrier. Some smearing artifact is visible at the bottom region of the polymer. The respective spectral results are given in (b). The first and second PCs gave non-informative distributions. PC 3 shows signal for various lipids, including Diacyl glycerols (m/z 550-620), PC 4 shows cholesterol ((M-OH)⁺ at m/z 369.4 and M⁺ at m/z 385.4), PC 5 shows silicone contamination (C₇H₂₁O₂Si₃⁺ at m/z 221.1, further identified from low-mass peaks in the corresponding region), PC 7 shows the polymer distribution, readily recognize from the m/z 44 spacing between the peaks, which exactly corresponds to the mass of one PEG unit. (c) Shows the PEG distribution in detail with characteristic 16 Da (K⁺ and Na⁺ difference or O loss) and 14 Da (CH₂ loss) intervals. The change from 0.2 to 0.3 values is due to binning down and, thus, rounding to 0.1 Da [105]. Reprinted with permission from Klerk LA, Dankers PYW, Popa ER, et al. TOF-secondary ion mass spectrometry imaging of polymeric scaffolds with surrounding tissue after in vivo implantation. Anal Chem 2010; 82:4337-4343. Copyright 2010 American Chemical Society

Figure 4

Imaging mass spectrometry and optical images of frozen section (8 μm) of the control vein (CV), arteriovenous fistula (AVF), and peripheral artery occlusive disease (PAD) samples Scale bar=200 μm. Ion intensity was normalized by total ion current. MSI of human AVF revealed the characteristic distribution of phospholipid molecules in the intima and media compared with that in the CV [107]. Reprinted with permission from Tanaka H, Zaima N, Yamamoto N, et al. Distribution of phospholipid molecular species in autogenous access grafts for hemodialysis analyzed using imaging mass spectrometry. Anal Bioanal Chem 2011; 400:1873-1880.