MRI Technique could lead to better Parkinson's treatments

As scientists try to slow or halt Parkinson's disease — the progressive brain disorder that afflicts Pope John Paul II and actor Michael J. Fox — it would be helpful if they could check their progress without opening up a bunch of skulls.

There is no blood test for the disease, characterized by nerve death in the substantia nigra, an area of brain that produces dopamine.

The disease is usually diagnosed based on symptoms, which appear only after large numbers of neurons have been destroyed.

Researchers at the University of Nebraska Medical Center announced Tuesday they have discovered a way to measure that cell death using MRI technology.

While not yet ready to become a diagnostic tool for Parkinson's in humans, the technique could accelerate the search for better treatments, said Michael Boska, associate professor in the UNMC Department of Radiology and principal investigator on the study.

"There's no question that this will be broadly applicable for therapeutic monitoring in mouse models and eventually humans," Boska said.

Parkinson's is characterized by limb tremor, slow movement, rigidity and poor balance. There is no cure. Treatment increases brain dopamine but has side effects.

"Typically, Parkinson's disease is not diagnosed in humans until about 50 percent of the brain neurons that control body movement are damaged," Boska said.

Using the new MRI technique, he was able to detect the disease in rodents when as little as 25 percent were damaged.

While technically demanding and requiring MRI scanners more powerful than those commonly in hospitals, the process should be easier in the larger brains of humans, he said.

After Alzheimer's disease, Parkinson's is the most common neurodegenerative disease, affecting one in 100 people older than 60. Approximately 500,000 people in the United States have Parkinson's disease, with as many as 50,000 new cases diagnosed each year.

News of the breakthrough appears this week in the Journal of Neuroscience, the leading publication for those studying the function of the nervous system.

The technique uses MRI technology to measure trace amounts of natural brain chemicals affected by Parkinson's.

Most MRI scans are created when the machine measures the relative density of water in various tissues, between that of bone and muscle, for instance.

Water molecules outnumber the chemicals by hundreds if not thousands of times, Boska said. The trick was to find those needles among the watery haystacks.

To make the chemicals visible, researchers subjected the brains to specific energy frequencies that excite only the water molecules. Then, before those molecules recover, a pulse of energy with broader frequency is used to take a picture of everything that is left.

"There are only a handful of labs in the entire world that could even do it, and we could do it reproducibly," Boska said.

Achieving the breakthrough involved engineering to improve the sensitivity of the MRI equipment and an evolution of technique.

The research was part of a collaborative effort involving the Departments of Radiology and Pharmacology, and the UNMC Center for Neurovirology and Neurodegenerative Disorders.

"Dr. Boska's use of MRSI is nothing short of cutting-edge for modeling disease in real-time," said Dr. Harris Gelbard of the University of Rochester (N.Y.) School of Medicine and a collaborator with the UNMC center on another brain disorder study.

"Most importantly, using MRSI has helped us determine whether neuroprotective drugs work in living animals, which is not always the case in cell culture studies. That Dr. Boska was able to utilize MRSI to study whether a very novel Parkinson's vaccine approach is neuroprotective (therapeutic) represents a vanguard for neuroscience."

Boska arrived at UNMC five years ago charged with development of an image research program within the department of radiology.

"This is the first major piece of work to come out of that development," Boska said. The department is already working on applying this breakthrough to work on ALS, Alzheimer's and HIV dementia.