Chem Rev. 2010 May 12;110(5):3237-77. doi: 10.1021/cr100012c.

Mass spectrometric imaging for biomedical tissue analysis.

Chughtai K¹, Heeren RM.

Author information

1: FOM-Institute for Atomic and Molecular Physics, Science Park 104, 1098 XG Amsterdam, The Netherlands.

PMID:: 20423155
PMCID:: PMC2907483
DOI:: 10.1021/cr100012c

[Indexed for MEDLINE]

Free PMC Article

Images from this publication.See all images (20)Free text

Figure 1

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 2

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 3

Desorption electrospray ionization (DESI). (a) Schematic representation of DESI desorption and ionization process; (b) brain tissue imaging analysis using DESI. Reprinted with permission from ref. Copyright 2008 Elsevier.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 4

Degradation of molecular species during a time course of incubation of the tissue at RT visualized by MALDI-MSI. (a) Coronal sections of mouse brain warmed on the target slide for 0, 0.5, 1, 1.75, 2.75 and 5.25 min. Upper and lower series are from two separate technical replicates. (b) Parasagittal sections of mouse brain incubated for 5 min and Sample 1 was heat treated (Denator system) to denature proteins immediately after tissue collection. Sample 2 is the corresponding untreated tissue and sample 3 was heat treated on the slide after sectioning and thaw mounting. Reprinted with permission from ref. Copyright 2008 Wiley Interscience.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 5

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 6

MALDI IMS analysis of fresh-frozen and ethanol-preserved sagittal mouse brain sections. (A) Photomicrographs of the sections after H&E staining; (a) cerebellum, (b) cerebral cortex, (c) main olfactory bulb, (d) midbrain, (e) hypothalamus, (f) pons, (g) hippocampal formation, (h) corpus callosum, (i) medulla, (j) thalamus. (B-I) Corresponding ion density maps from a subset of proteins observed in common from both sections. Reprinted with permission from ref. Copyright 2008 American Chemical Society.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 7

Analysis of the effect of OCT on MALDI signals from rat liver. (A) Procedure where OCT is used to adhere the tissue to the sample stage but does not come into contact with the sliced tissue. The resulting spectrum shows many intense signals between m/z 4500 and 10 500. (B) The tissue was embedded in OCT and attached to the sample stage. The resulting spectrum contains only about half of the signals as that in (A). Reprinted with permission from ref. Copyright 2003 Wiley Interscience.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 8

Analysis of matrix crystallization from solutions of different matrix concentration. Solutions of sinapinic acid in 50: 50 acetonitrile/0.1% TFA in water at concentrations of (A) 10 mg/mL, (B) 20 mg/mL, and (C) saturated (>30 mg/mL). The spectra obtained from solutions spotted on mouse liver tissue sections showed that the greater the concentration of matrix, the greater the crystal coverage, and the better the resulting mass spectrum. Reprinted with permission from ref. Copyright 2003 Wiley Interscience.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 9

Analysis of matrix crystallization on tissue. Comparison of three different matrices, (A) SA, (B) DHB, and (C) HCCA at concentration 20 mg/mL (in 50:50 acetonitrile/0.1% TFA in water). SA and HCCA form dense crystals on the tissue, while DHB does not crystallize on the rim of the spot. Reprinted with permission from ref. Copyright 2003 Wiley Interscience.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 10

An optical image of H&E-stained sagittal mouse brain section showing the anatomy of the brain and selected ion images from a dry-coated serial sagittal section showing the phospholipid patterns in the brain. CB, cerebellum; CC, corpus callosum; CTX, cerebral cortex; HY, hypothalamus; M, medulla; P, pons; TH, thalamus; V4, fourth ventricle; VL, lateral ventricle; PC, phosphatidylcholine; SM, sphingomyelin. Reprinted with permission from ref. Copyright 2008 Elsevier.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 11

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 12

High-resolution MALDI images of a mouse cerebellum. The left panel shows the H&E-stained optical image of a mouse brain section. The overlaid phospholipid images show the localization of PC(40:6) (m/z 872 in light blue) to the cerebellar cortex, PC(36:1) and PC(38:4) (m/z 826 in the middle and m/z 810 on the left in red) to the cerebellar nucleus, and PC(38:6) (m/z 844 in green) to the granule cell layer. Reprinted with permission from ref. Copyright 2008 Elsevier.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 13

MS Imaging in IMS mode of a nominally isobaric peptide (RPPGFSP) and lipid PC(34:2) deposited onto a mouse liver thin tissue section in the pattern of an X. (A) An optical image of the patterned matrix/analyte spots deposited on the tissue section. (B) A zoomed view in the region of PC(34:2) and RPPGFSP for a representative IMS of a mixture of the two analytes. (C) Extracted ion intensity maps for the peptide (left, green), the lipid (center, blue), and an overlay of the two maps at 50% transparency. Reprinted with permission from ref. Copyright 2007 Wiley Interscience.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 14

IMS diagram of ions detected from a rat brain tissue section covered with DHB. Ions of different drift time but overlapping m/z can be separated from each other. Reprinted with permission from ref. Copyright 2007 Wiley Interscience.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 15

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 16

Analysis of a tissue section from an EPPE tumor bearing mouse lung specimen. The photomicrograph of the displayed section, which was H&E-stained following MSI acquisition and matrix removal, shows several histologically different regions: (a) lung, (b) lung tumors (areas in yellow dotted lines), (c) heart, (d) upper respiratory pathways, (e) left heart ventricle, (f) aorta, (g) right pulmonary artery, (h) artery, (i) bronchus. Five distinct ion density maps from proteins which distinctively localize in different areas of the section are displayed. Reprinted with permission from ref. Copyright 2008 American Chemical Society.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 17

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 18

Negative-ion DESI mass spectra of bromophycolides. DESI-MS image (200 μm resolution) of bromophycolide A/B chloride adduct ion m/z 701 on C. serratus surface, indicating that bromophycolide “hot spots” correspond to pale patches. Reprinted with permission from ref. Copyright 2009 PNAS.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 19

MALDI imaging of proteins from an Anopheles gambiae male antenna. Ion images of four proteins are reported: m/z 8015, m/z 8565, m/z 11941 and m/z 13936 respectively in panel A, B, C, and D, showing a different distribution across the antenna. Reprinted with permission from ref. Copyright 2008 Dani et al.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.

Figure 20

MALDI images of (A) AMP, (B) ADP, (C) UDP-GlcNac, (D) F-1,6-biP (fructose-1,6-bisphosphate), and (E) GTP (guanosine triphosphate) acquired in the negative ion mode from a rat brain section coated with 9-AA matrix. (F) Optical image of a brain tissue section after 9-AA deposition and analysis by MALDI imaging with a 50 μm pixel size. Reprinted with permission from ref. Copyright 2009 American Chemical Society.

Mass Spectrometric Imaging for biomedical tissue analysis

Chem Rev. ;110(5):3237-3277.