The goal of the proposed studies is to develop high resolution 3-D Imaging Mass Spectrometry (IMS) technology to a level that it is capable of delivering high resolution images in a practical time frame. High spatial resolution IMS (~10 um) will be employed with tissue preparation protocols that provide 1 um matrix crystal sizes and high speed lasers (.3 kHz) to provide data on multiple serial sections in a efficacious and timely manner. It is planned to develop the protocols that would allow peptides, proteins, lipids and drugs and other small molecules to be tracked in a 3-D manner in a tissue volume. In addition, work is planned to accomplish the significant biocomputational effort needed to deal with data dimensionality and size reduction, normalization of ion intensities for the relative quantitation of images both within a single 2-D experiment and across serial sections of a tissue volume for 3-D reconstruction, registration of the sections with anatomic fidelity, and generation of a 3-D images of individual molecules in a practical time domain. Several important biological problems will be addressed with this technology;1) assessment of the 3-D molecular distributions and boundaries of striosomes in the striatum of the mouse brain, substructures implicated in neuropsychiatric disorders such as Parkinsonism, Huntington's Disease, and obsessive-compulsive disorder, 2) 3-D mapping of molecular events in glioma growth, progression, and maintenance, both in the tumor and microenvironment, in the optic nerve of a mouse model with linkage to existing 3-D microscopy images in the brain atlas, 3) Co-registration of 3-D IMS data with other imaging modalities;studies of the disposition and metabolism of contrast agents used for PET imaging, the elucidation of molecular aspects in diffusion weighted imaging by MRI, and the co-registration/correlation of molecular events obtained by IMS with MR relaxation data. This work will bring together several powerful imaging modalities and, through the unique attributes of each, gain a combinatorial advantage in understanding whole tissue dynamics. In one aim, it is planned to combine microscopy and IHC measurements, MRI and IMS as part of a single 3-D volume that is easily interrogated using standard internet tools.

Public Health Relevance

3-D Imaging Mass Spectrometry will provide an exciting new approach for mapping molecular constituents in tissue volumes in an unbiased manner (i.e., without the need for antibodies). The information obtained will allow chemical annotation, improved interpretation and validation to classical imaging technologies, i.e., MRI, PET and microscopy. A major innovative aspect of the work is that it can provide data relevant to the anatomy of the whole organ or entire animal with high spatial fidelity and unmatched molecular specificity.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Edmonds, Charles G
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Vanderbilt University Medical Center
Schools of Medicine
United States
Zip Code
Moore, Jessica L; Becker, Kyle W; Nicklay, Joshua J et al. (2014) Imaging mass spectrometry for assessing temporal proteomics: analysis of calprotectin in Acinetobacter baumannii pulmonary infection. Proteomics 14:820-8
Grove, Kerri J; Voziyan, Paul A; Spraggins, Jeffrey M et al. (2014) Diabetic nephropathy induces alterations in the glomerular and tubule lipid profiles. J Lipid Res 55:1375-1385
Manier, M Lisa; Spraggins, Jeffrey M; Reyzer, Michelle L et al. (2014) A derivatization and validation strategy for determining the spatial localization of endogenous amine metabolites in tissues using MALDI imaging mass spectrometry. J Mass Spectrom 49:665-73
Verbeeck, Nico; Yang, Junhai; De Moor, Bart et al. (2014) Automated anatomical interpretation of ion distributions in tissue: linking imaging mass spectrometry to curated atlases. Anal Chem 86:8974-82
Dittwald, Piotr; Nghia, Vu Trung; Harris, Glenn A et al. (2014) Towards automated discrimination of lipids versus peptides from full scan mass spectra. EuPA Open Proteom 4:87-100
Libes, Jaime M; Seeley, Erin H; Li, Ming et al. (2014) Race disparities in peptide profiles of North American and Kenyan Wilms tumor specimens. J Am Coll Surg 218:707-20
Yang, Junhai; Caprioli, Richard M (2014) Matrix pre-coated targets for high throughput MALDI imaging of proteins. J Mass Spectrom 49:417-22
Seeley, Erin H; Wilson, Kevin J; Yankeelov, Thomas E et al. (2014) Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease. Bone 61:208-16
Gessel, Megan M; Norris, Jeremy L; Caprioli, Richard M (2014) MALDI imaging mass spectrometry: spatial molecular analysis to enable a new age of discovery. J Proteomics 107:71-82
Zavalin, Andre; Yang, Junhai; Haase, Andreas et al. (2014) Implementation of a Gaussian beam laser and aspheric optics for high spatial resolution MALDI imaging MS. J Am Soc Mass Spectrom 25:1079-82

Showing the most recent 10 out of 136 publications