TY - JOUR
T1 - Precise co-registration of mass spectrometry imaging, histology, and laser microdissection-based omics
AU - Dewez, Frederic
AU - Martin-Lorenzo, Marta
AU - Herfs, Michael
AU - Baiwir, Dominique
AU - Mazzucchelli, Gabriel
AU - De Pauw, Edwin
AU - Heeren, Ron M. A.
AU - Balluff, Benjamin
N1 - Funding Information:
This research was financially supported in part through the LINK program of the Province of Limburg (The Netherlands). FD received support from the Joint Imaging Valley program of the University of Liège and the Maastricht University. MML received financial support from the European Union (ERA-NET TRANSCAN 2; Grant No. 643638).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/9
Y1 - 2019/9
N2 - Mass spectrometry imaging (MSI) is an analytical technique for the unlabeled and multiplex imaging of molecules in biological tissue sections. It therefore enables the spatial and molecular annotations of tissues complementary to histology. It has already been shown that MSI can guide subsequent material isolation technologies such as laser microdissection (LMD) to enable a more in-depth molecular characterization of MSI-highlighted tissue regions. However, with MSI now reaching spatial resolutions at the single-cell scale, there is a need for a precise co-registration between MSI and the LMD. As proof-of-principle, MSI of lipids was performed on a breast cancer tissue followed by a segmentation of the data to detect molecularly distinct segments within its tumor areas. After image processing of the segmentation results, the coordinates of the MSI-detected segments were passed to the LMD system by three co-registration steps. The errors of each co-registration step were quantified and the total error was found to be less than 13 mu m. With this link established, MSI data can now accurately guide LMD to excise MSI-defined regions of interest for subsequent extract-based analyses. In our example, the excised tissue material was then subjected to ultrasensitive microproteomics in order to determine predominant molecular mechanisms in each of the MSI-highlighted intratumor segments. This work shows how the strengths of MSI, histology, and extract-based omics can be combined to enable a more comprehensive molecular characterization of in situ biological processes.
AB - Mass spectrometry imaging (MSI) is an analytical technique for the unlabeled and multiplex imaging of molecules in biological tissue sections. It therefore enables the spatial and molecular annotations of tissues complementary to histology. It has already been shown that MSI can guide subsequent material isolation technologies such as laser microdissection (LMD) to enable a more in-depth molecular characterization of MSI-highlighted tissue regions. However, with MSI now reaching spatial resolutions at the single-cell scale, there is a need for a precise co-registration between MSI and the LMD. As proof-of-principle, MSI of lipids was performed on a breast cancer tissue followed by a segmentation of the data to detect molecularly distinct segments within its tumor areas. After image processing of the segmentation results, the coordinates of the MSI-detected segments were passed to the LMD system by three co-registration steps. The errors of each co-registration step were quantified and the total error was found to be less than 13 mu m. With this link established, MSI data can now accurately guide LMD to excise MSI-defined regions of interest for subsequent extract-based analyses. In our example, the excised tissue material was then subjected to ultrasensitive microproteomics in order to determine predominant molecular mechanisms in each of the MSI-highlighted intratumor segments. This work shows how the strengths of MSI, histology, and extract-based omics can be combined to enable a more comprehensive molecular characterization of in situ biological processes.
KW - Mass spectrometry imaging
KW - Laser microdissection
KW - Microproteomics
KW - Co-registration
KW - Intratumor heterogeneity
U2 - 10.1007/s00216-019-01983-z
DO - 10.1007/s00216-019-01983-z
M3 - Article
C2 - 31263919
SN - 1618-2642
VL - 411
SP - 5647
EP - 5653
JO - Analytical and Bioanalytical Chemistry
JF - Analytical and Bioanalytical Chemistry
IS - 22
ER -