MRI adapted to track infection, swelling

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Global positioning systems have long been used to track vehicles, people, children, dogs -- anything that moves or might get lost.

So imagine a new technology that modifies magnetic resonance imaging to track immune cells to follow cellular processes or pinpoint hidden areas of infection and inflammation anywhere inside the human body.

A research team based at Carnegie Mellon University has modified an MRI system to track immune cells tagged with fluorine atoms to areas of infection or inflammation. The image generated allows concentrations of fluorine to be visualized, denoting immune-cell reaction to inflammation in three dimensions.

Written by Deepak K. Kadayakkara, a post-doctoral research fellow at Johns Hopkins University School of Medicine who earned his doctoral degree at CMU last May, the study was published recently in the journal Laboratory Investigation. Eric T. Ahrens, a CMU associate professor of biological sciences, led the project.

The system initially was used to track inflammation from irritable bowel disease, which currently requires invasive colonoscopies and biopsies for diagnoses that aren't always successful. But Mr. Ahrens said the new MRI technology can track inflammation anywhere in the body by generating images of cells tagged with fluorine.

"Basically what we've developed is a platform not only for irritable bowel disease, but any localized inflammatory condition such as organ transplant rejection, occult infections, the inflammation component of cancer, traumatic brain injury, other injuries and wounds, multiple sclerosis and cardiovascular disease," he said.

The new technology also would allow a clinician to monitor inflammation before, during and after drug treatment.

The process involves tagging macrophages, T-cells or cells not involved with the immune response with fluorine-19, the natural fluorine isotope, whose signals, created when energized by MRI, are captured to produce an image.

The first step is formulating fluorine-19 polymers into a nanoformulation that the immune cell consumes as a foreign particle in the blood stream. Millions of immune cells containing fluorine then search body-wide for infections to battle. The accumulation of fluorine visualized by MRI identifies a scene of inflammation or infection.

Jeff Bulte, a radiology professor and the director of cellular imaging at the Johns Hopkins Institute for Cell Engineering, isn't involved in the project but said he's familiar with it. He said he'd be "very happy" if Mr. Ahrens' project becomes a clinical routine for tracking cells.

Conventional MRI technology generates an image of anatomical structures, including organs and bones, by energizing protons, whose signals are used to create an image. Fluorine, unlike protons, doesn't exist naturally in measurable quantities in the body, so it stands out in images generated by the MRI process but at different frequencies.

The new technology attached to conventional MRI equipment produces an image of cells tagged with fluorine then superimposes that image atop a traditional proton-induced MRI image to show their precise location relative to anatomical structures.

Key to project success, Mr. Bulte said, has been the Ahrens team's success in formulating the right fluorine compounds and software to quantify how much fluorine is present in the image. Fluorine has been proven safe for humans in other medical procedures and treatments.

"The pieces are all there and clinical studies already have been done with fluorinated compounds, which are biologically safe," Mr. Bulte said. "Things are moving forward at a rapid pace."



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