New x-ray technique shows promise for early Alzheimer's diagnosis

A new, concentrated x-ray technique that can visualize amyloid beta (Aß) plaque could be developed into a method for early diagnosis of Alzheimer's disease, according to research published in the July edition of NeuroImage.

Many believe that Aß plaques actually cause the disease, thus a major goal is to develop a drug that removes the plaques from the brain. However, before drug therapies can be tested, researchers need a non-invasive, safe and cost-effective way to track the plaques' number and size, the authors wrote. Yet, Aß plaques are extremely small and conventional techniques such as CT poorly distinguish between the plaques and other soft tissue such as cartilage or blood vessels.

"These plaques are very difficult to see, no matter how you try to image them," said Dean Connor, a former postdoctoral researcher at the Department of Energy's (DoE) Brookhaven National Laboratory in Upton, N.Y., now working for the University of North Carolina in Durham. "Certain methods can visualize the plaque load...But these methods cannot provide the resolution needed to show us the properties of individual Aß plaques."

Diffraction-enhanced imaging (DEI) might provide the extra imaging power. DEI uses synchrotron x-rays to visualize not only bone, but also soft tissue in a way that is not possible using standard x-rays. In contrast to conventional sources, synchrotron x-ray beams are thousands of times more concentrated into a narrow beam. The result is typically a lower x-ray dose with a higher image quality.

In this study, researchers from Brookhaven and Stony Brook University used DEI in a high-resolution mode called micro-CT to visualize individual plaques in a mouse-brain model of Alzheimer's disease. The results not only revealed detailed images of the plaques, but also proved that DEI can be used on whole brains to visualize a range of anatomical structures without the use of a contrast agent.

The images are similar to those produced by high-resolution MRI, with the potential to even exceed MRI images in resolution, according to Connor. "The contrast and resolution we achieved in comparison to other types of imaging really is amazing," he said. "When DEI is used, everything just lights up."

The radiation dose used for this study is too high to safely image individual Aß plaques in humans, but the results provide researchers with promising clues.

"Now that we know we can actually see these plaques, the hope is to develop an imaging modality that will work in living humans," Connor said. "We've also now shown that we can see these plaques in a full brain, which means we can produce images from a live animal and learn how these plaques grow."

Funding for this study was provided by the National Institutes of Health, the National Cancer Institute, and Brookhaven Lab's Laboratory Directed Research and Development program. The National Synchrotron Light Source is funded by the Office of Basic Energy Sciences within the DoE Office of Science.

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