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Advanced Computational Analysis for IMS

Automated Anatomical Interpretation

We have developed a strategy to integrate IMS data with anatomical atlases. This capability provides automated anatomical examination of IMS data [1].

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Figure 1. An example of the process for automated anatomical interpretation. See manuscript for figure details.  Biochim Biophys Acta (7):967-977


Advanced Registration and Analysis of MALDI Imaging Mass Spectrometry Measurements through Autofluorescence Microscopy

The correlation of imaging mass spectrometry (IMS) with histopathology can help relate novel molecular findings obtained through IMS to the well-characterized and validated histopathology knowledge base. The quality of correlation between these two modalities is limited by the quality of the spatial mapping that is obtained by registration of the two image types. In this work, we develop novel workflows for MALDI IMS-to-microscopy data registration and analysis using nondestructive IMS-compatible wide field autofluorescence (AF) microscopy combined with computational image registration. First, a substantially automated procedure for high-accuracy registration between IMS and microscopy data of the same section is described that explicitly links the MALDI laser ablation pattern imaged by microscopy to its corresponding IMS pixel. Subsequent examination of the registered data allows for high-confidence colocalization of image features between the two modalities, down to single-cell scales within tissue. Building on this IMS-microscopy spatial mapping, we furthermore demonstrate the automated spatial correlation between IMS measurements from serial sections. This AF-registration-driven inter-section analysis, using a combination of nonlinear AF-to-AF and IMS-to-AF image registrations, can be applied to tissue sections that are prepared and imaged with different sample preparations (e.g., lipids vs proteins) and/or that are measured using different spatial resolutions. Importantly, all registrations, whether within a single section or across serial sections, are entirely independent of the IMS intensity signal content and thus unbiased by it.

Software for this tool can be downloaded here.

Figure 2: Overview of the workflow for the above described automated, high accuracy IMS-to-microscopy registration. Abstract and graphical abstract: Patterson et al., Advanced Registration and Analysis of MALDI Imaging Mass Spectrometry Measurements through Autofluorescence Microscopy, Anal Chem, 2018.


References

Verbeeck N, Spraggins JM, Murphy MJM, Wang HD, Deutch AY, Caprioli RM, Van de Plas R. (2016) Connecting imaging mass spectrometry and magnetic resonance imaging-based anatomical atlases for automated anatomical interpretation and differential analysis. Biochim Biophys Acta (7):967-977