Mass Spectroscopy, MRI Reveal New View of Body’s Response to Infection

A new imaging advance offers a three-dimensional (3D) window into the body’s response to infection--and the ability to detect the proteins involved in the response--could lead to innovative new biomarkers and therapeutic agents for infectious diseases.

Vanderbilt University (Nashville, TN, USA) scientists from many fields combined magnetic resonance imaging (MRI) and imaging mass spectrometry to visualize the inflammatory response to a bacterial infection in mice. The techniques, described June 14, 2012, in the journal Cell Host & Microbe, provide insights into the characteristics of proteins not previously involved in the inflammatory response.

Access to distinctive resources at Vanderbilt made the unprecedented 3D infection imaging possible, according to Eric Skaar, PhD, Ernest Goodpasture chair in pathology and one of the senior coauthors of the study. “The studies in this paper couldn’t have happened at any other university, because the resources simply don’t exist at most schools,” Dr. Skaar said.

The resources include animal imaging technologies available through the Vanderbilt University Institute of Imaging Science (VUIIS), directed by John Gore, PhD, and imaging mass spectrometry technologies available through the Mass Spectrometry Research Center (MSRC), directed by Richard Caprioli, PhD, Drs. Gore and Caprioli are also senior coauthors of the paper.

Dr. Skaar and his team were interested in imaging infection in 3D--in the whole animal--while also being able to identify the proteins that are generated at sites of infection. Imaging mass spectrometry is a unique technology that directly measures proteins, lipids, and other metabolites and maps their distribution in a biopsy or other tissue sample. Ahmed Attia, PhD, a former member of Dr. Skaar’s group now on the faculty at Cairo University (Egypt), infected mice with Staphylococcus aureus, he then brought the infected animals to Daniel Colvin, PhD, in the VUIIS, who imaged them with magnetic resonance imaging (MRI). Kaitlin Schroeder and Erin Seeley, PhD, in the MSRC then conducted imaging mass spectrometry studies.

Fusing the two technologies and multiple data sets accurately required the expertise of Kevin Wilson, MESc, in the VUIIS, who developed algorithms to show consolidated 3D views of the inflammatory response. “This is another example of the multimodality approach we have been pursuing in general within the Imaging Institute,” Dr. Gore said.

The technologies allow the investigators to see one image of an infected animal, look at how proteins of the immune system are responding, and identify where the infected tissue is located, according to Dr. Skaar. “Part of the strength of this work is not where the research is now, but where it allows us to go from here.”

The scientists’ strategy now is to identify “proteins that are important at the interface between the host and the pathogen-- the battleground between the immune system and the bacteria,” Dr. Skaar said. The researchers will study the proteins they identify to discover new biomarkers for infection, which could improve diagnostic tools, or new targets for therapeutic intervention.

The technologies available through the MSRC and the VUIIS will be useful for any investigator interested in imaging the inflammatory response, which has roles in infectious diseases, cancer and autoimmune diseases, according to Dr. Skaar. Moreover, although the technology is not noninvasive--as imaging mass spectrometry requires tissue sections--it could be applied to tissues removed from patients, such as tumors.

“Imaging mass spectrometry is extremely valuable for the discovery process because it does not require a target-specific reagent such as an antibody--that is, you do not have to know in advance what you’re looking for in order to correlate molecular changes with disease outcome,” Dr. Caprioli said. “An area of intense interest is the application of this technology to molecular pathology.”

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