Diffraction-Enhanced Imaging Developed for Early Alzheimer's Disease Diagnosis

The technique has previously been used to look at tumors in breast tissue and cartilage in the human knee and ankle joints, but a new study is first to assess its ability to visualize a class of miniscule plaques that are a hallmark feature of AD.

The scientists, from the U.S. Department of Energy's (DOE) Brookhaven National Laboratory (Upton, NY, USA), published their findings in the July 2009 issue of the journal NeuroImage. Researchers have long known that Alzheimer's disease is associated with plaques, areas of dense built-up proteins, in the affected brain. Many also believe that these plaques, called amyloid beta (Aß) plaques after the protein they contain, actually cause the disease. 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 noninvasive, safe, and cost-effective way to track the plaques' number and size.

That is no simple task: Aß plaques are extremely small--on the micrometer scale, or one millionth of a meter. Moreover, conventional techniques such as computed tomography (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 Dr. Dean Connor, a former postdoctoral researcher at Brookhaven Lab now working for the University of North Carolina (Chapel Hill). "Certain methods can visualize the plaque load, or overall number of plaques, which plays a role in clinical assessment and analysis of drug efficacy. But these methods cannot provide the resolution needed to show us the properties of individual Aß plaques.”

A technique developed at Brookhaven, called diffraction-enhanced imaging (DEI), might provide the extra imaging power researchers need. DEI, which makes use of extremely bright beams of X-rays available at synchrotron sources such as Brookhaven's National Synchrotron Light Source, is used to visualize not only bone, but also soft tissue in a manner that is not possible using standard X-rays. In contrast to conventional sources, synchrotron X-ray beams are thousands of times more intense and extremely 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 utilized DEI in a high-resolution mode called microcomputed tomography 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 wide range of anatomic structures without the use of a contrast agent.

The images are similar to those produced by high-resolution magnetic resonance imaging (MRI), with the potential to even exceed MRI pictures in resolution, according to Dr. 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--the ultimate goal--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,” Dr. 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.”

To make a diffraction-enhanced image, X-rays from the synchrotron are first tuned to one wavelength before being beamed at an anatomic structure or slide. As the monochromatic (single wavelength) beam passes through the tissue, the X-rays scatter and refract, or bend, at different angles depending on the characteristics of the tissue. The subtle scattering and refraction are detected by what is called an analyzer crystal, which diffracts (alters the intensity) of the X-rays by different amounts according to their scattering angles.

The diffracted beam is passed onto a radiographic plate or digital recorder, which documents the differences in intensity to show the interior structural details.

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Brookhaven National Laboratory