Pathogenesis of epilepsy in magnetic resonance imaging and under the microscope

How can the development of epilepsy be anticipated? This is the question Academy Research Fellow Alejandra Sierra Lopez tries to find answers to by combining magnetic resonance imaging (MRI) and tissue research methods.

Epilepsy can emerge, for example, as a result of a blow to the head. The mechanisms by which the injury leads to the development of epilepsy are not fully known. Recognising changes in the brain that are indicative of epilepsy makes it possible to find increasingly efficient ways to treat and even prevent the disease.

"MRI is used to diagnose epilepsy, but with the current methods it is difficult to notice epilepsy-related changes in the microstructure of the brain. When working with patients, one often has to settle for not being able to make a diagnosis on the basis of MRI," Sierra Lopez says.  

She is keen on searching for MRI biomarkers to anticipate the development of epilepsy. With a five-year funding package from the Academy of Finland, she aims to apply novel MRI methods to studying the microstructure of the brain in order to find biomarkers of the precursors of epilepsy that is related to head injury. Biomarkers can be very subtle changes in the brain which indicate that the development of epilepsy has begun.

"For instance, these could include structural changes in the hippocampus, which we have observed in animals following brain damage."

Evolving methods

Sierra Lopez's success in the competition for Academy of Finland funding was boosted by a multidisciplinary approach and the combination of different research methods. Up until now, she worked in Professor Olli Gröhn's research group, which uses MRI methods to study diseases of the nervous system. She combines MRI with neurobiological tissue research, in which Academy Professor Asla Pitkänen's epilepsy research group and its animal models are an important partner.

The development of epilepsy is documented in animals using MRI, and these findings are compared to changes observed in brain tissue samples. The project uses several MRI methods, including diffusion tensor imaging, and novel techniques, high-angular-resolution diffusion imaging, double-pulsed-field-gradient and sweep imaging with Fourier transformation. 

"The methods available in tissue research are also evolving. New electron microscopy methods make it possible to obtain three-dimensional images of all structures in a tissue sample. It is important to understand how the information obtained by different MRI methods is related to the real structure of the tissue and to the changes taking place over the course of the disease."

The suitability of the new biomarkers and imaging methods for clinical use will eventually be tested in a group of patients following head injury.

An important career step

Sierra Lopez says that being appointed as Academy Research Fellow of the Academy of Finland is an important step in a research career. It is also a starting point for gathering a research group of her own.

"At the moment, the workload is really heavy. I have to make progress in my own research and coordinate the work of others at the same time."

Sierra Lopez came to Finland from Madrid, Spain, where she studied chemistry and biochemistry at the Complutense University of Madrid and the National Distance Education University, UNED. She wrote her doctoral dissertation in the field of biochemistry at the Alberto Sols Biomedical Research Institute on a grant which made it possible to spend some time abroad. Her supervisor contacted Professor Gröhn who welcomed Sierra Lopez to Kuopio to study MRI.

"I wanted to learn something completely new and was given an opportunity to study the use of MRI in the monitoring of the treatment response of brain tumour gene therapy. After three months, I could even speak a little bit of Finnish."

After defending her PhD in 2006, an opportunity to return to Kuopio as a postdoc researcher opened up.

"It was nice to come back somewhere familiar where I didn't have to start everything from scratch. Soon, I was busy studying epilepsy and histology, and so far, I've also managed to sort out funding, even if it is sometimes in small bits."

Always carrying a camera

Besides research, Sierra Lopez also has another passion: photography and cameras, of which she currently owns 30. She has her camera bag with her even on conference trips, and she has won a prize in the Kuopio Photo Marathon.

"I don't take photos of people, because I'm pretty shy. Instead, I think I have taken a photo of every tree in Kuopio," she says, laughing. "Photography takes time because I combine different cameras and techniques."

Her photographs have a dark atmosphere and bright colours – perhaps an influence from MRI and the microscope images she works with.

"It's kind of like bringing a hobby to work when I take images on a microscope and teach others to do it, too. It's important to me that my research articles have informative yet beautiful images."
Sierra Lopez says that it was easy to settle in Finland. "I don't need a socially active life, like many of my friends back home. My life here in Finland is quiet and home-oriented, but the people are nice."

Although her working language is English, she has worked hard to learn Finnish. Finnish language skills are useful in the community college's knitting class, for example, where she started by learning something very Finnish: how to knit a woollen sock.

Text: Ulla Kaltiala Photo: Raija Törrönen