2 research outputs found
Histology-Guided High-Resolution Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging
Mass spectrometry imaging (MSI) is
widely used for clinical research
because when combined with histopathological analysis the molecular
signatures of specific cells/regions can be extracted from the often-complex
histologies of pathological tissues. The ability of MSI to stratify
patients according to disease, prognosis, and response is directly
attributable to this cellular specificity. MSI developments are increasingly
focused on further improving specificity, through higher spatial resolution
to better localize the signals or higher mass resolution to better
resolve molecular ions. Higher spatial/mass resolution leads to increased
data size and longer data acquisition times. For clinical applications,
which analyze large series of patient tissues, this poses a challenge
to keep data load and acquisition time manageable. Here we report
a new tool to perform histology guided MSI; instead of analyzing large
parts of each tissue section the histology from adjacent tissue sections
is used to focus the analysis on the areas of interest, e.g., comparable
cell types in different patient tissues, thereby minimizing data acquisition
time and data load. The histology tissue section is annotated and
then automatically registered to the MSI-prepared tissue section;
the registration transformation is then applied to the annotations,
enabling them to be used to define the MSI measurement regions. Using
a series of formalin-fixed, paraffin-embedded human myxoid liposarcoma
tissues, we demonstrate an 80% reduction of data load and acquisition
time, thereby enabling high resolution (mass or spatial) to be more
readily applied to clinical research. The software is freely available
for download
Multimodal Mass Spectrometry Imaging of <i>N</i>‑Glycans and Proteins from the Same Tissue Section
On-tissue
digestion matrix-assisted laser desorption/ionization mass spectrometry
imaging (MALDI-MSI) can be used to record spatially correlated molecular
information from formalin-fixed, paraffin-embedded (FFPE) tissue sections.
In this work, we present the <i>in situ</i> multimodal analysis
of <i>N</i>-linked glycans and proteins from the same FFPE
tissue section. The robustness and applicability of the method are
demonstrated for several tumors, including epithelial and mesenchymal
tumor types. Major analytical aspects, such as lateral diffusion of
the analyte molecules and differences in measurement sensitivity due
to the additional sample preparation methods, have been investigated
for both <i>N</i>-glycans and proteolytic peptides. By combining
the MSI approach with extract analysis, we were also able to assess
which mass spectral peaks generated by MALDI-MSI could be assigned
to unique <i>N</i>-glycan and peptide identities