Integrating spatially resolved three-dimensional MALDI IMS with in vivo magnetic resonance imaging

Abstract

We have developed a method for integrating three dimensional-volume reconstructions of spatially resolved matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) ion images of whole mouse heads with high-resolution images from other modalities in an animal-specific manner. This approach enabled us to analyze proteomic profiles from MALDI IMS data with corresponding in vivo data provided by magnetic resonance imaging.

Figure 1

Coregistered MALDI IMS and magnetic resonance data from a whole mouse head. (a) The red-green-blue image plane shows a sagittal section from the optical blockface volume. The axial magnetic resonance image represents the quantitative transverse relaxation (T₂) component of the tissue, rendered in grayscale on a scale of 0 (black) to 150 ms (white). The MALDI IMS data for Pea15 are volume rendered as the yellow and green cloud. (b) The same rendering as in a is shown for Fabp5. Each axis is measured in centimeters and the white outline represents the extent of the blockface volume. The MALDI IMS data are rendered in color representing arbitrary units of intensity with from 0 (blue) to 1 (red).

Figure 2

Intermodal validation of the MALDI IMS signature for Pea15, a biomarker for grade III glioma. (a) Coregistered MALDI IMS and magnetic resonance data from a whole mouse head. Top, corresponding slices from coregistered blockface, T_1w’, T_2w and diffusion weighted volumes, rendered in normalized grayscale (0 is black, 1 is white). Bottom, the same slice from each modality with the MALDI-IMS protein distribution overlaid. The ranges for all of the imaging data were normalized to 1 with corresponding red-green-blue and grayscale color bars shown. (b) Results of ROI analysis for manually selected ROIs that corresponded to normal and tumor tissue. Representative ROIs in a from a single slice are shown in the blockface image in a.