MRI Technology Noninvasively Locates, Quantifies Specific Cells

Magnetic resonance imaging (MRI) is not just for capturing detailed images of the body's anatomy. Due to newly developed innovative imaging reagents and technology, MRI can be used to visualize, with "exquisite” specificity, cell populations of interest in the living body.

The ability to noninvasively locate and track cells, such as immune cells, should greatly aid the study and treatment of cancer, inflammation, and autoimmune diseases, as well as provide a tool for advancing clinical translation of the emerging field of cellular regenerative medicine, by tracking stem cells, for example.

Carnegie Mellon University (Pittsburgh, PA, USA) scientist Dr. Eric Ahrens presented his findings at the 236th national meeting of the American Chemical Society in Philadelphia, PA, USA, in August 2008. "With our technology we can image specific cells in real-time with exquisite selectivity, which allows us to track their location and movement and to count the apparent number of cells present. We then use conventional MRI to obtain a high-resolution image that places the labeled cells in their anatomical context,” commented Dr. Ahrens, an associate professor of biological sciences at the Mellon College of Science.

The ability to track the movement and eventual location of specific immune cells is critical for understanding the cells' role in disease and therapeutic mechanisms and for developing effective cell-based therapeutics. Other MRI techniques for visualizing cells use metal-based contrast agents, which can make it difficult to clearly identify labeled cells in the body, according to Dr. Ahrens. "The large background signal from mobile water and intrinsic tissue contrast differences can often make it challenging to unambiguously identify regions containing these metal-ion labeled cells throughout the body, which is the current state of the art,” Dr. Ahrens said.

Dr. Ahrens's new approach--fluorocarbon labeling--solves this problem by producing images that distinctly show the labeled cells at their precise location in the body. Dr. Ahrens first labeled the cells of interest with a perfluoropolyether (PFPE) nanoemulsion, which is a colloidal suspension of tiny fluorocarbon droplets. He then introduced the labeled cells into an animal subject and tracked the cells in vivo using 19F MRI.

Whereas traditional MRI detects the nuclear magnetic resonance signal from protons contained in the mobile water in tissue, 19F MRI detects the signal from the nucleus of the fluorine atom. Fluorine is not typically present in the body at sufficient concentrations to detect, so when Dr. Ahrens labeled cells with PFPE, he detected this fluorine tracer with MRI after the cells are transplanted into the body. The researchers have recently used the PFPE technology to label and track dendritic cells and T cells in a mouse model of type I diabetes, a disease in which immune cells infiltrate the pancreas, attacking and damaging the body's own cells.

"Right now we're using our technology to image key cell types involved in autoimmune diseases like type I diabetes, but our cellular MRI agents also can be adapted to label other cell types, including cells from bone marrow and stem cells. A key long-term application of our technology is to label and monitor cell-based therapeutics in humans,” Dr. Ahrens said.

Recent developments in cell-based therapeutics research have focused on training immune cells to counteract diseases including cancer and diabetes and on directing stem cells to regenerate damaged tissues. Noninvasively visualizing these therapeutic cells in patients after transfer can be a difficult hurdle, according to Dr. Ahrens, and any approach that can speed up the testing of these treatments will be extremely useful.

"Ideally, we would label therapeutic cells with our cellular MRI agents before they are implanted into a patient. In this way, we could use MRI to visualize the movement of the therapeutic cells in the patient to monitor whether they migrate to and remain in the desired tissues,” explained Dr. Ahrens.

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