Researchers create 3-D images of Alzheimer's-linked plaque

Researchers at the Medical Center recently became the first scientists to produce three-dimensional images of plaque-blobs of cellular garbage-found in the brains of patients with Alzheimer's disease.

"Up to now, we have had to stain a tissue sample... and look at it under a microscope," said Dr. Helene Benveniste, lead researcher and associate professor of anesthesiology.

Currently, doctors cannot diagnose Alzheimer's in living patients with certainty because researchers can only obtain tissue samples after a patient has died.

As a consequence, scientists do not know whether brain plaque accompanies the onset of Alzheimer's or whether it is an after-product of the disease.

The new method, although performed only on mice for now, may pave the way for a non-invasive diagnosis of Alzheimer's in humans and a much better understanding of how the disease works.

Benveniste explained that the imaging technique would also allow researchers to track the development of brain plaques over a long period of time, as opposed to current invasive procedures that are limited to one-time snapshots of the brain's condition.

During the imaging procedure, the mouse is anaesthetized to keep it motionless. The mouse's head is then surrounded by a strong magnetic scanner that takes hundreds of separate images. This information is relayed to a computer, which uses the images to slowly assemble a complete three-dimensional image.

Benveniste's team used high-resolution magnetic resonance microscopy to create the 3-D images.

The MRM is a derivative of the more popular medical imaging tool magnetic resource imaging-also known as MRI-but it has a 1,000-fold greater spatial resolution.

Allan Johnson, professor of radiology and biomedical engineering and director of the Duke Center for In Vivo Microscopy, helped Benveniste with the technical aspects of the procedure. "We let her use our unique toys," he said.

Johnson's most difficult task was to tweak the instruments to ensure that they focused on the actual plaques of mostly neuronal material rather than other items such as brain coiling and water concentration.

Benveniste said these are the same variables that technologically complicate the creation of three-dimensional images in humans; scientists must develop stronger scanning techniques which provide better resolution for the more complex beings.

"I am excited about such prospects, but I am not holding my breath for it," she said.

Benveniste began her study of Alzheimer's patients' brain tissues one year and a half ago.

She knew that in vivo plaque scans-scans for plaque performed inside living organisms-had been attempted before but were ultimately abandoned because the necessary technological advancements had not been made yet. "Unless the engineering and physics aspects of the study are done, no bioscience gets done either," Johnson said, explaining the importance of technological development.

In the future, Benveniste said she plans to use the new procedure to study mice genetically engineered to develop Alzheimer's and test the effectiveness of numerous drugs that are being developed to combat Alzheimer's in humans.

However, she said these results will have to be interpreted with caution because of the difference in complexity between human and mouse brains; she added that further clinical trials will be necessary.

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