Multiplex Mass-Spectrometry Imaging for Cancer research

When adding more than three or four fluorophores to a microscopy sample, their exciting wavelength ranges will start to overlap, making it impossible to separate signals coming from each fluorophore. This spectral overlap limits the potential of traditional microscopy to give a comprehensive view of the biological sample. Few techniques have by-passed this limit, like Mass-Spectrometry Imaging that is using metal beads attached to antibodys to “image” up to 50 proteins at a time. A powerful laser burns a small piece of the sample (1 squared micrometer) and the volatile metal beads are recognized with a mass-spectrometer. Mass-spectrometry imaging is a very promising imaging technique to analyse the spatial organization of a tissue while having access to an unprecented number of proteins.

We use mass-spectrometry images to analyse the tumor micro-environment of different types of cancer: small cell-line lung cancer (SCLC), Chronic Lymphocytic Leukemia (CLL), or Diffuse large B cell lymphoma (DLBCL). We investigate the infiltration of immune cells in the tumor, the changes of protein expressions in different compartments, and the effect of advanced cancer treatments.

From the analysis point of view, the detection and segmentation of cells is challenged by the low resolution of mass-spectrometry images (1 squared micrometer) compared to traditional microscopy. We develop crafted methods to detect all relevant celltypes, with special care for rare cell types, and further compare the protein expressions and tissue architectures.