Wednesday, August 21, 2013

Image post 8: mapping live brains

This image from UAB Research illustrates the improving brain maps that promise to reveal the mechanisms behind complex, neurological diseases.

A MRI technology called diffusion tractography captured this image of a living rat brain. Tractography is a 3-D modeling technique that visually represents nerve pathways in the brain using data collected by diffusion tensor imaging (DTI).

DTI visualizes nerve pathways known collectively as white matter that connect the various parts of the brain via long bundles of nerve cells. It shows whether or not bundles of white matter fibers run in the same direction, but not in which direction. Tractography does that.

Since developed by researchers at Washington University School of Medicine in St. Louis, it has given the field a more detailed look at brain structures, especially living brains. Taken together, these new MRI technologies promise to improve understanding of neurological disorders like schizophrenia and Alzheimer's disease and the consequences of head trauma. They also may one day help neurosurgeons better avoid cutting nerves during surgeries.

In particular, tractography reveals connections that can be measured in living human subjects and measurements that can be made simultaneously across the entire brain. The Human Connectome Project is capitalizing on these strengths to build more accurate brain maps. The image was created in the lab of Hyunki Kim, Ph.D., associate professor in the departments of Radiology and Biomedical Engineering and faculty in the UAB Comprehensive Cancer Center.

Monday, August 12, 2013

Scratch-and-Sniff test for Parkinson's disease

Many of us grew up with iconic scratch-and-sniff technology. Maybe kids in your class had stickers that smelled like berries or popcorn when scratched. Mom's fashion magazine offered pungent samples of the latest perfume. According to its Wikipedia entry, everything from Nintendo video game packaging to a smell guide promoting the movie Spy Kids to Katy Perry's album Teenage Dream (cotton candy) have featured micro-fragrance coatings. Apparently, 3M came up with it by accident in the '60s during experiments on a copying technology.

Given the technology's pop-culture history, I was surprised to read a recent story in the Birmingham News that it is now being used to test people for early signs of Parkinson's disease. The story features video of David Standaert, M.D., Ph.D., chair of the Department of Neurology within the UAB School of Medicine, demonstrating the test. We asked him to talk about the science behind the test, as well as his team's involvement in a related study funded by the Michael J. Fox Foundation.

Show notes from the podcast: 

1:15 While the credit for the discovery of microfragrance coatings goes to 3M, it was the University of Pennsylvania that spent years developing the standard, scientific method for testing a person's ability to smell. Penn researchers must have had their reasons for including in the test certain smells -- dill pickle, grass, smoke, peach, turpentine, etc. -- but an explanation will have to wait for another post.

1:51 Researchers have known for years that people with Parkinson's disease lose their ability to smell, but not why. Neither did anyone make a connection between scratch-and-sniff technology and Parkinson's diagnosis for many years. Researchers first noticed the change because Parkinson's patients typically lose weight. Without the ability to smell, food loses it taste.

2:23  Old theories had it that Parkinson's disease, by interfering with muscle movement, meant that patients could not sniff as well. That idea was debunked by the work of German neuroanatomist Dr. Heiko Braak in 2003. His painstaking study revealed that among the first brain regions damaged as Parkinson's disease develops is the olfactory center.

4:07. People also lose their sense of smell after head trauma or exposure to harsh chemicals. This led to the major questions in the field like "what does it mean to lose your sense of smell?" and "can smell tests accurately reveal a change in the brain that points to pre-symptomatic, Parkinson's?" If you take a group of people who have lost the ability to smell and follow them through the years, what does that reveal?

4:40  The classic indicator that someone has Parkinson's disease is that their limbs begin to shake (tremor). In recent years it became clear that such a person's dopamine neurons have already lost about 70 percent of their function. An earlier warning sign is a must.

5:05 The damage of caused by Parkinson's to dopamine neurons probably starts a decade before hands start to tremble. Researchers once that the death of such nerve cells was the first thing to happen in the disease process, but not believe it happens in the middle.

6:10 So what happens first? Over the years, researchers had noted that people who would later go on to develop Parkinson's disease first suffered from a strange group of symptoms: sleeplessness, constipation and of course, loss of the ability to smell. With these symptoms so disparate, researchers did not realize for many years that they are influenced by buildup of the same protein, called alpha-synuclein, in the nervous systems of Parkinson's patients.

6:46 Those taking the Parkinson's sniff tests scratch a series of smell pads and answer questions about what they smell. Dr. Standaert's team tests people over 60 years of age, with thee expectation that about a third of them, if they have a sufficiently abnormal sense of smell based on a standard numerical score, will turn out to be in the early stages of Parkinson's disease. So if you are over 60 and can no longer smell normally, you have 66 percent chance of not having Parkinson's and a 33 percent chance of having it (up from 1 or 2 percent risk for the general population).

8:15 Another major thrust of the team's work is to study how nerve cells and nerve pathways that employ the major signaling chemical dopamine to pass on messages are different in people who have lost their sense of smell due to Parkinson's disease. It if turns out that people with with smell loss have a corresponding drop in dopamine function, the team will follow them over several years in hopes of revealing further details on early disease-causing mechanisms in Parkinson's disease.

11:00 Many labs are rigorously pursuing experimental drugs meant to slow the progression of Parkinson's disease. Should one or more of them be approved for use in the relatively near future, one can envision the creation of smell test screening programs for everyone as they turn 60. Those that do poorly, would then be referred for further testing, and preventive treatment could begin much earlier. In terms of a public health intervention, it would be relatively low cost because you could mass mail the sniff test cards with return postage, and people could mail them back in.

Those interested in more information or in participating in future trials should look up the Parkinson’s Progression Marker Initiative, or the Michael J. Fox Foundation survey. Those interested in local trials in Birmingham call also email Stephanie Guthrie at