Technique "Lights Up" Iron in Brains of Patients with Parkinson Disease
 Mark Davidson, Ph.D. University of Florida |
 Joanna Collingwood, Ph.D. Keele University |
A new imaging technique highlights the altered distribution of metal ions in the brains of patients with Parkinson disease (PD).
Researchers from the University of Florida in Gainesville and Keele University Research Institute for Science and Technology in Medicine in Staffordshire, Great Britain, have combined synchrotron imaging with MR imaging to "map" iron levels within affected brain tissue. The beams generated by the synchrotron are around 100 billion times brighter than a standard hospital X-ray machine and with special sample preparation give scientists a unique view of iron distribution in brain samples.
While numerous peer-reviewed studies have associated accumulation of metals in brain tissue with neurological disorders—in the case of PD, that metal is iron—researchers do not fully understand the role metals play in the disease process.
Researchers utilized cadaver brain tissue samples from patients with PD to gain new information about how the disease process alters iron distribution and chemistry in the brain. Two of the study's principal investigators presented findings earlier this year at the annual meeting of the American Association for the Advancement of Science (AAAS) in Chicago.
Mark Davidson, Ph.D., a graduate research scientist at the University of Florida described how the intense power of the synchrotron X-ray beam helped their research. "Because of the way the synchrotron physics work, it's almost like a laser," he said. "It's extraordinarily intense at the sample. What that allows us to do is to detect a very tiny quantity of material in a large specimen."
Dr. Davidson likened searching for the extremely tiny iron particles to looking for a dinner plate in the state of Florida. "We tune the X-rays so all we can see is 'dinner plates,'" he explained. "Then suddenly the three dinner plates in the whole state light up like light bulbs, so we say 'Aha! There's a dinner plate in Tampa and one in Orlando and one in Jacksonville.'"
Dr. Davidson took the analogy further: "We can sweep that energy and look at how the 'dinner plate' absorbs the X-rays. I can also tell you if the 'dinner plate' is right-side up or upside down or whether it's red or blue."
That ability to isolate or "light up" iron ions, said Dr. Davidson, opens the door to a new understanding of not only where the iron is distributed, but also how its chemical makeup is altered over time.
The study was conducted at Diamond, the U.K.'s national synchrotron, and the Advanced Photon Source, a synchrotron located at Argonne National Laboratory near Chicago.
Study Takes Typical Mapping Focus One Step Further
While synchrotron spectroscopy is used in other types of research, Keele University research fellow Joanna Collingwood, Ph.D., explained the difference in this study's aim. "Several other groups are also using the synchrotron microfocus spectroscopy approach to study tissues, but the majority of researchers concentrate on the mapping," said Dr. Collingwood. "Our team puts a lot of emphasis on combining two approaches—mapping followed by the collection of energy spectra from points of interest in the maps. The latter is what provides us with information about the chemical and mineral form of the element of interest."
Some observers cautioned that this research will not immediately result in live patient screening abilities, although earlier PD detection is clearly a shared goal. Matthew T. Walker, M.D., an associate professor of radiology and chief of neuroradiology at the Feinberg School of Medicine of Northwestern University in Chicago, said he is very interested in the team's use of synchrotron spectroscopy as a means to understand the role of iron in PD and the potential impact their findings could have on patient imaging strategies.
"While based at the molecular level, this research advances our knowledge of Parkinson disease and may improve our ability to develop imaging strategies that identify or confirm the disease in the earliest stages," said Dr. Walker, who also serves as chair of the neuroradiology subcommittee of the RSNA Education Exhibits Committee.
"Parkinson disease remains a clinical diagnosis, in part because contemporary imaging findings are fairly subtle and not necessarily present in the earliest stages of the disease," Dr. Walker continued. "If further synchrotron research identifies specific iron-containing compounds or conformational states that are particularly toxic to the brain, it will provide another target for molecular and MR imaging research."
Study Supports Progress Toward Early Detection, Improved Diagnosis
| Researchers from the University of Florida in Gainesville and Keele University Research Institute for Science and Technology in Medicine in Staffordshire, Great Britain, have combined synchrotron imaging with MR imaging to "map" iron levels within affected brain tissue in patients with Parkinson disease. Shown is brain tissue with affected cells and an iron map of the affected tissue.
Image courtesy Mark Davidson, Ph.D. From "Toward New Therapeutic Approaches for Parkinson Disease," presented at the 2009 annual meeting of the American Association for the Advancement of Science. |
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Dr. Collingwood said the synchrotron study—offering information about the distribution, relative concentration, and storage form of iron—is designed to provide additional information about the way that iron is handled in the vulnerable regions in the Parkinson brain, in the hope that the data can be used to inform the development of MR imaging for early detection and improved diagnosis.
The research may lead to the design of better chelators to remove the iron from affected brains, added Dr. Davidson. "If we can understand the chemistry, we can design chelators that remove only those iron compounds which have moved into states that can induce chain reactions leading to oxidative stress in brain tissue," he said. "Just by understanding the chemistry well enough maybe we can intervene at the beginning of this process."
Dr. Walker said if the primary goal is to better understand PD at a molecular and biochemical level and guide therapeutic development in the form of prevention or medical treatment such as chelation, then the direct translation and impact on patients could be felt sooner than later. "What is exciting to me is the potential to target specific iron compounds for dedicated imaging development much like sodium MR imaging in stroke," he said. He added that while he is optimistic, "Imaging patients at that level will take vast improvements on the technical side, primarily spatial resolution, if this is ever going to translate into mainstream imaging paradigms."
Dr. Collingwood said she and her colleagues are working at high-resolution and high-field to maximize the amount of information they can obtain. "It is the additional information from these techniques that would be used to inform clinical imaging," she said. "We are not proposing direct translation of research-strength fields and resolutions to a patient population."
The U.K. and Florida teams are initiating research with a 3 T clinical MR unit to compare what they learn from donor tissues to what can be observed in clinical settings. Dr. Collingwood said the group hopes to confer with other researchers around the world already studying aspects of clinical observation of iron with MR to make the best use of the synchrotron findings for future clinical practice.
