Header Molecular Tumor Diagnostics

MALDI Imaging Unit – Targeting the protein landscape of cancer

Matrix-associated laser-based desorption and ionization imaging, in short MALDI Imaging, combines two major fields of bioanalytical methods: molecule analysis determined by means of mass spectra according to time-of-flight masses (m/z), and the macroscopic anatomy of the tissue compartments. Regions of interest (ROI) of human cancer tissue slides defined by pathologists are translated into mass spectra pattern and can be used for subsequent bio-statistical analyses of protein, peptide or lipid composition and quantification. In addition to the knowledge gained from differing mass spectra in e.g. tumor versus normal tissue areas, morphologically indistinguishable tumors can be subdivided and analyzed for molecule-dependent heterogeneity by segmentation of mass intensities at a very high resolution (down to 5x5 micrometer).

In addition to the significance of conventional MALDI analysis for routine diagnostics and to conducting medical research projects using experimental setups, the MALDI Imaging Unit is researching on bioinformatic workflows and deep learning pipelines to utilize the big data information e.g. for automation purposes.

Figure 1: MALDI Imaging instrument. Rapflex MALDI Tissuetyper (Bruker Daltonik GmbH) to perform MALDI Imaging analyzation based on time of flight molecule mass detection.

Figure 1: MALDI Imaging instrument. Rapflex MALDI Tissuetyper (Bruker Daltonik GmbH) to perform MALDI Imaging analyzation based on time of flight molecule mass detection.

Figure 2: Visualization of mass spectra pattern on tissue slides via segmentation. A pancreatic tumor sample was analyzed by MALDI imaging. Left side: Visualization of mass spectra as segmentation map based on trained regions of interest of specified tissue compartments. Right side: Grayscale image scan of the same tissue. Red: pancreatic tissue, orange: tumor tissue, dark red: stroma, yellow: fatty tissue, pink: lymph node, lilac/rose: background.

Research focus

  • Tumor classification of rare tumor types
  • Segmentation of (intra-) tumor heterogeneity
  • Lipid, protein and peptide mass spectra identification of novel tumor subtypes
  • Generation of a consistently growing database of tumor vs normal tissue mass spec data
  • MALDI segmentation pipelines based on Deep learning
  • 3D MALDI imaging approaches

Samples types for MALDI imaging:

  • Fresh frozen tissue
  • Formalin fixed and paraffin embedded (FFPE) tissue
  • Samples with and without enzyme digestion on slide
  • Embedded organoids, spheres or cell culture blocks

Technical information:

  • Positive and negative flight mode detected by linear or reflector detector
  • Mass range (positive mode e.g.):  peptides: 600-3200 m/z, proteins 1000-500.000 m/z
  • Scan range: 5x5µm to 150x150µmresulting field size
  • Automated batch run option
  • External calibration and quality controls provided
  • Big data storage (data file from 20-100GB)
Figure 3: Mass spectra of tumor region.  Example of  one mass spectra pattern in a range of 600-3200 m/z of  a tumor region (FFPE sample).

Figure 3: Mass spectra of tumor region. Example of one mass spectra pattern in a range of 600-3200 m/z of a tumor region (FFPE sample).

Coordination

Dr. rer. med. Pia Hönscheid
Group leader
E-Mail: pia.hoenscheid(at)uniklinikum-dresden.de
Phone: +49 (0)351 45813038

Director

Prof. Dr. med. Gustavo Baretton
Director of Institute of Pathology Dresden
E-Mail: Gustavo.Baretton(at)uniklinikum-dresden.de
Phone: +49 (0)351 4583000

Team

Dr. rer. nat. Julia Hilsenbeck,
Biologist
E-Mail: Julia.hilsenbeck(at)uniklinikum-dresden.de
Phone: +49(0)351 458-11854

Christian Sperling
Medical Technical Assistant
E-Mail: Christian.Sperling(at)uniklinikum-dresden.de
Phone: +49 (0)351 458-13009

Maxime le Floch  
MD Student
E-Mail: maxime.lefloch(at)medforum-dresden.de   
Phone: +49(0)351 458-3009

Linna Sommer,
MD Student
E-Mail: Linna.Sommer(at)uniklinikum-dresden.de
Phone: +49(0)351 458-16226