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

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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.

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Figure 1: Coregistered MALDI IMS and magnetic resonance data from a whole mouse head.
Figure 2: Intermodal validation of the MALDI IMS signature for Pea15, a biomarker for grade III glioma.

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Acknowledgements

We would like to thank J. True, R. Baheza and the staff of the Vanderbilt University Institute of Imaging Science Center for Small Animal Imaging for their assistance in collecting the imaging data presented here. Financial support was provided by the US National Institutes of Health Institute of Biomedical Imaging and Bioengineering, Cancer Institute, Institute of Neurological Disorders and Stroke and the Institute of General Medical Sciences.

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Authors and Affiliations

  1. Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, 37232, 1161 21st Avenue South, Tennessee, USA

    Tuhin K Sinha, Thomas E Yankeelov & John C Gore

  2. Department of Chemistry, Vanderbilt University, Nashville, 37232, 1161 21st Avenue South, Tennessee, USA

    Sheerin Khatib-Shahidi & Richard M Caprioli

  3. Department of Physics and Astronomy, Vanderbilt University, Nashville, 37232, 1161 21st Avenue South, Tennessee, USA

    Thomas E Yankeelov & John C Gore

  4. Department of Biomedical Engineering, Vanderbilt University, Nashville, 37232, 1161 21st Avenue South, Tennessee, USA

    Thomas E Yankeelov & John C Gore

  5. Department of Neurological Surgery, Vanderbilt University, Nashville, 37232, 1161 21st Avenue South, Tennessee, USA

    Khubaib Mapara & Moneeb Ehtesham

  6. Department of Cancer Biology, Vanderbilt University, Nashville, 37232, 1161 21st Avenue South, Tennessee, USA

    Moneeb Ehtesham

  7. Department of Biochemistry, Vanderbilt University, Nashville, 37232, 1161 21st Avenue South, Tennessee, USA

    D Shannon Cornett & Richard M Caprioli

  8. Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, 37232, 1161 21st Avenue South, Tennessee, USA

    Benoit M Dawant

  9. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, 37232, 1161 21st Avenue South, Tennessee, USA

    John C Gore

Authors
  1. Tuhin K Sinha
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  2. Sheerin Khatib-Shahidi
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  3. Thomas E Yankeelov
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  4. Khubaib Mapara
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  5. Moneeb Ehtesham
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  6. D Shannon Cornett
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  7. Benoit M Dawant
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  8. Richard M Caprioli
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  9. John C Gore
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Contributions

T.K.S. helped to develop the techniques presented here and assisted in collecting and analyzing the results. S.K.-S. helped to acquire the blockface and MALDI IMS data. T.E.Y. helped to acquire the in vivo magnetic resonance data. K.M. implanted and provided the mouse with a tumor-laden brain. M.E. provided support and expertise with the tumor model. D.S.C. provided expertise in collecting the MALDI IMS data. B.M.D. helped to develop accurate coregistration techniques for the MALDI IMS and magnetic resonance alignment. R.M.C. provided support and expertise for the MALDI IMS data collection. J.C.G. helped to develop the techniques presented here and provided expertise with data analysis and magnetic resonance data collection.

Corresponding author

Correspondence to Tuhin K Sinha.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–4 and Supplementary Methods (PDF 1821 kb)

Supplementary Movie 1

Reconstructed blockface volume of a whole mouse head. (MOV 3915 kb)

Supplementary Movie 2

Blockface reconstruction results for whole animals. (MOV 3365 kb)

Supplementary Movie 3

Coregistered volumetric MALDI IMS data with in vivo magnetic resonance imaging in a tumor-laden mouse brain. (MOV 9343 kb)

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Sinha, T., Khatib-Shahidi, S., Yankeelov, T. et al. Integrating spatially resolved three-dimensional MALDI IMS with in vivo magnetic resonance imaging. Nat Methods 5, 57–59 (2008). https://doi.org/10.1038/nmeth1147

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  • DOI: https://doi.org/10.1038/nmeth1147

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