In experiments on mice, scientists report that they have successfully combined two brain imaging techniques – magnetic resonance imaging (MRI) and positron emission tomography (PET).
MRI is prized for its ability to reveal abnormalities in brain structure, such as tumors, swelling and atrophy (shrinkage). PET, which works by detecting small molecules that have been radioactively tagged and injected into the body, can probe the brain's biochemistry and metabolism. For example, PET has been used to study moment-to-moment shifts in the chemical signals known as neurotransmitters.
By combining PET and MRI, researchers should be able to perform unique structure-function studies of the brain and other tissues. They also envision combining PET with functional MRI (fMRI) – which looks at the brain's oxygen consumption as a measure of brain activity – to examine multiple aspects of brain function at once. If successful, they might be able to simultaneously track how a drug affects brain activity (by fMRI) and how it affects the abundance and location of neurotransmitters and their receptors (by PET).
The technology is not quite ready for use in humans, says Simon Cherry, Ph.D., a professor in the Department of Biomedical Engineering at the University of California at Davis. His latest study, published in the Proceedings of the National Academy of Sciences* and supported in part by the National Institute of Neurological Disorders and Stroke (NINDS), describes a miniature PET/MRI machine designed to acquire brain and whole-body scans from mice.
Ciprian Catana, M.D., Ph.D., the first author of the study and Dr. Cherry's former graduate student, is collaborating with industry to develop full-size PET/MRI scanners for clinical use. Dr. Catana is now a junior faculty member in the Radiology Department at Massachusetts General Hospital.
Dr. Cherry and his group reported prototype PET/MRI scanners a little more than a decade ago, but the performance of those early machines was poor due to incompatibility. Conventional PET scanners use photomultiplier tubes – a relative of the cathode ray tubes in televisions and television cameras – to convert low-level light into electrical currents. Unfortunately, photomultiplier tubes are extremely sensitive to the magnetic fields created by MRI scanners. In their latest study, the researchers replaced the photomultiplier tubes with avalanche photodiodes, a newer type of light detector that builds up an "avalanche" of electrical current in response to light. Developing a clinical grade scanner is largely a matter of scaling up the mouse-size scanner, the researchers say.
Meanwhile, the mouse-size scanners themselves are useful for studying pathology and testing potential therapies in mouse models of disease, they say.
In the PNAS study, Drs. Cherry and Catana show how the mouse-size PET/MRI scanner can be used to probe the characteristics of tumors growing in live mice. In one experiment, MRI revealed the outlines of a tumor, about the size of pencil eraser. Meanwhile, PET revealed cells in the tumor's inner core that failed to take up radio-labeled glucose and thus were probably dead. Combining MRI with other types of PET – that is, using other radio-labeled substances – could reveal other information, such as the predominant cells types within a tumor and whether they have become malignant.
Angelique Louie, Ph.D., also a professor of biomedical engineering at UC Davis, theorizes that PET/MRI could be used to diagnose people at risk for heart attack and stroke. The predominant cause of heart attack and stroke is plaque – fatty material on the inside of blood vessels – that can break apart and send clots into the bloodstream. Recent studies suggest that inflammatory cells build up at the inside edges of plaques that are highly vulnerable to rupture. In experiments on mice, Dr. Louie is using PET/MRI to identify these vulnerable plaques. MRI can provide a high-resolution view of the plaque, while PET and special radiotracers that stick to inflammatory cells can reveal the density and distribution of the cells inside the plaque, she says.
Finally, Russell Jacobs, Ph.D., a member of the multi-disciplinary Beckman Institute at Caltech and a co-author of the PNAS study, plans to use combined PET/fMRI to study mouse models of depression and other psychiatric diseases. He hopes that his work will help answer some "sticky questions" relevant to treatment, he says.
For example, although antidepressants are known to affect neurotransmitter signaling, researchers do not understand how altered neurotransmitters translate into altered mood. Using PET/fMRI to simultaneously view neurotransmitter signaling and brain activity in mouse models – and eventually in human patients – could enable researchers to better define the basis for mood changes and to improve antidepressant drugs, Dr. Jacobs says.
NINDS is a component of the National Institutes of Health (NIH) within the Department of Health and Human Services. The NIH — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research. It investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
-By Daniel Stimson, Ph.D.
*Catana, C et al. "Simultaneous In Vivo Positron Emission Tomography and Magnetic Resonance Imaging." Proceedings of the National Academy of Sciences, March 11, 2008, Vol. 105 (10), pp. 3705-3710.