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Profiles in Brain Sciences: Alexandra Badea, PhD

Tuesday, August 13, 2019
A Badea

Understanding and visualizing the changes Alzheimer’s makes to the brain is an incredibly complex challenge, requiring the use of quantiative biomarkers, such as those provided by imaging of human and animal subjects, and other research fields. Fortunately, the work of Alexandra Badea, PhD, falls within all of these domains. For our next “Profiles in Brain Science” interview, Badea talks to us about the multidisciplinary nature of her work. She also discusses how her research may help provide insight into changes happening in the brains of animal models or patients with Parkinson’s disease, autism spectrum disorder, or epilepsy, and how radiology has become better, faster, and safer over the past decade. Finally, Badea also shares her loves of travel, music, and exploring North Carolina when she’s not at work.

What is your role within the Neurology Department? What does a typical day for you look like?
My main interest is in neuroimaging, with a focus on Alzheimer’s disease (AD). I am interested in both humans and animal models of AD and how we can use imaging to better understand this multifactorial disease. I am developing magnetic resonance imaging-based biomarkers and modeling approaches that integrate multiple biomarkers, and that may help relate brain changes to behavioral changes. For this reason, my day should ideally incorporate developing the experimental protocols that lead to meaningful data acquisitions, image analysis, writing manuscripts and grants, developing collaborations and sharing thoughts with students. I also like to spend time learning new things every day. In reality I am limited to doing one, or at best three of these things in any one day. And then there are days when I need to debug code, tame instruments, and tune phrases – but I am not sure you wanted to know about these days.

In addition to your appointment with the Neurology Department, you’re also parts of the Departments of Radiology and Biomedical Engineering. How do each of these areas overlap with your work in Neurology?

This was an easy question, as I believe that we need to integrate knowledge from different domains, and that boundary domains are fertile ground for creativity. For example, we need to learn about the brain to decide what kind of imaging is appropriate, what kind of biomarkers would be interesting. We need engineering knowledge to decide on the type of instrumentation to be used, the analysis to be done, and efficient processing. And we always need math to help us think through problems. There are many pieces to the brain puzzle and what happens during aging and AD; and I am very lucky and very grateful to be in such a collaborative environment, allowing for interdisciplinary cross talk among departments.

You recently lead a “Research in Progress” meeting focusing on your investigation identifying vulnerable brain networks in animal models. Can you briefly describe that work?

This is the result of collaborative work using mouse models of late onset Alzheimer’s disease, based on the genetic risk conferred by the APOE4 genotype, when compared to the APOE3 genotype. We have used novel mouse models developed in Dr. Carol Colton’s lab, and imaged the brains of these animals using high resolution diffusion weighted imaging on the 9.4T CIVM magnet. Finally, we registered the brains into the space of an in house developed MRI atlas of the mouse brain, so that we can compare the properties of these regions and their interconnections.

The connections may provide sensitive biomarkers since subtle changes in cellular density, myelination, or toxicity can each influence the brain connectome in a small but significant way. Moreover, the brain networks may serve as highways for propagating Alzheimer’s pathology in humans. While our mice are not humans they can replicate aspects of Alzheimer’s disease and help us understand the bases of selective brain networks’ vulnerability in aging and disease. To help identify such brain networks we used on the diffusion weighted imaging sensitized to 46 angular direction, and based on these images we reconstructed models of the connections among the 332 brain regions provided by the atlas. We worked together with the team developing DIPY in order to be able to adapt such tools to small animal brain imaging. In collaboration with Dr. David Dunson and Wenlin Wu we set on a quest to identify the top connections discriminating between the two genotypes. Finally, we examined the properties of these connections (each representing one matrix point in the connectome), and observed how the properties changed along the fibers, differentiating between genotypes, and also sex.

How will the results of that research help us better understand or treat neurological conditions?
I think developing tools to identify vulnerable networks in aging and AD is a translational avenue. I am excited to work on and apply such tools at BIAC to help understand the aging human brain, and particularly in relation to genetic risk for AD. Similar tools could be used to help identify connectopathies in other conditions including Parkinson’s disease, autism spectrum disorder, or epilepsy. However, the effects of novel interventions or the relations to molecular mechanisms may need to be explored using animal models, before humans can benefit directly from them.

What do you see as the biggest change in radiology as a field since you earned your doctorate?

Going digital, dose reduction, and new contrast agents to help us see what we can see better, faster, and safer. Besides these, I think radiology has become more quantitative, and focused on data/information science. Let us not forget that advances in computing have enabled imaging applications that would not have been practical otherwise.

What important or exciting change(s) in the field do you see coming over the next decade?
It is rather clear that machine learning has  already reached critical momentum.

What other passions or hobbies do you have outside of the Department?
There are few things I do not like, so this is a difficult question. I like music very much, and hope that one day I can really learn to play the guitar. I love traveling and meeting new people, and learning about their traditions and folklore. I love spending time with family and cooking together with the kids. And we all like biking around town. I am grateful to be living in such a beautiful area, where you can hike in the forest in town, or bike to the Maple View Creamery, the American Tobacco Trail, or Jordan lake. We can do a day trip to the Smoky Mountains, or the ocean, maybe go to the Outer Banks for a weekend. One co-worker has inspired me to coach for the YMCA, and I have really enjoyed playing basketball with the girls’ team for the past two seasons.

Do you have a photo of yourself in a non-work setting that you can share?
I am sharing a photo of a first learning session in sailing on the waters of the Sound side in Hatteras. There were hilarious moments when we had to pick up the sail from the water, or try hard to navigate against the wind, but learning to flow with the wind was the best part. Hard work, and lots of fun!

Badea takes up windsailing in the Outer Banks in this photo.