Abstract

The brain functions through chemical interactions between many different cell types, including neurons and glia. Acquiring comprehensive information on complex, heterogeneous systems requires multiple analytical tools, each of which have unique chemical specificity and spatial resolution. Multimodal imaging generates complementary chemical information via spatially localized molecular maps, ideally from the same sample, but requires method enhancements that span from data acquisition to interpretation. We devised a protocol for performing matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance-mass spectrometry imaging (MSI), followed by infrared (IR) spectroscopic imaging on the same specimen. Multimodal measurements from the same tissue provide precise spatial alignment between modalities, enabling more advanced image processing such as image fusion and sharpening. Performing MSI first produces higher quality data from each technique compared to performing IR imaging before MSI. The difference is likely due to fixing the tissue section during MALDI matrix removal, thereby preventing analyte degradation occurring during IR imaging from an unfixed specimen. Leveraging the unique capabilities of each modality, we utilized pan sharpening of MS (mass spectrometry) ion images with selected bands from IR spectroscopy and midlevel data fusion. In comparison to sharpening with histological images, pan sharpening can employ a plethora of IR bands, producing sharpened MS images while retaining the fidelity of the initial ion images. Using Laplacian pyramid sharpening, we determine the localization of several lipids present within the hippocampus with high mass accuracy at 5 μm pixel widths. Further, through midlevel data fusion of the imaging data sets combined with k-means clustering, the combined data set discriminates between additional anatomical structures unrecognized by the individual imaging approaches. Significant differences between molecular ion abundances are detected between relevant structures within the hippocampus, such as the CA1 and CA3 regions. Our methodology provides high quality multiplex and multimodal chemical imaging of the same tissue sample, enabling more advanced data processing and analysis routines.

Original languageEnglish (US)
Pages (from-to)11572-11580
Number of pages9
JournalAnalytical chemistry
Volume90
Issue number19
DOIs
StatePublished - Oct 2 2018

Fingerprint

Mass spectrometry
Brain
Infrared radiation
Imaging techniques
Chemical analysis
Ions
Infrared imaging
Data fusion
Tissue
Ionization
Desorption
Cyclotron resonance
Image fusion
Lasers
Neurons
Infrared spectroscopy
Data acquisition
Fourier transforms
Image processing
Pixels

ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Multimodal Chemical Analysis of the Brain by High Mass Resolution Mass Spectrometry and Infrared Spectroscopic Imaging. / Neumann, Elizabeth K.; Comi, Troy J.; Spegazzini, Nicolas; Mitchell, Jennifer W.; Rubakhin, Stanislav; Gillette, Martha L; Bhargava, Rohit; Sweedler, Jonathan V.

In: Analytical chemistry, Vol. 90, No. 19, 02.10.2018, p. 11572-11580.

Research output: Contribution to journalArticle

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T1 - Multimodal Chemical Analysis of the Brain by High Mass Resolution Mass Spectrometry and Infrared Spectroscopic Imaging

AU - Neumann, Elizabeth K.

AU - Comi, Troy J.

AU - Spegazzini, Nicolas

AU - Mitchell, Jennifer W.

AU - Rubakhin, Stanislav

AU - Gillette, Martha L

AU - Bhargava, Rohit

AU - Sweedler, Jonathan V

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