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Chat with Dr. Thomas Mathivet about In Vivo Cardiovascular Imaging of the Brain

Dr. Thomas Mathivet, working at the Cardiovascular Institute in Paris, France, was interviewed by Dr. Luis Alvarez, Product Application Manager, during Leica Microsystems Meets Science 2019 in Mannheim, Germany. He discusses his research on the cardiovascular system in the brain. The goal is a better understanding of specific disease conditions, such as brain tumors. Dr. Mathivet’s team performs real-time imaging of the brain in live animals and the results play a significant role in the development of new intervention strategies for these pathologies. The SP8 DIVE spectrally tunable multiphoton microscope has changed the approach of his team to imaging. The need to visualize simultaneously with 5 to 6 different channels, not possible with traditional systems, is now met. Dr. Mathivet has found that the new imaging capabilities of the SP8 DIVE enable him to see more, including label-free visualization of collagen to study the brain’s structural aspects.

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Transcript of the Video-Interview

Dr. Alvarez: Hello Thomas, we are very happy to have you here in Mannheim at Leica (Microsystems) and perhaps you can tell us a little bit about yourself in two or three sentences and your research interests?

Dr. Mathivet: So, I am a researcher in France at the Cardiovascular Institute of Paris looking to understand the physiopathology linked to vessel patterning and vessel behavior in disease models, specifically in neurovascular pathology, such as strokes, tumors like gliomas which are primary tumors of the brain, or also arteriovenus malformations. The idea of this research is to find a way to cure vessels which are damaged in the brain during those pathological events - to allocate better the drugs to treat the actual disease, as it is one of the challenges in pharma to get your product to the specific site where it should act.

Dr. Alvarez: Okay, so in your research you also do a lot of imaging?

Dr. Mathivet: Sure, imaging is probably the center of our research. Basic research imaging first on post-operative samples or sections or also cells and so on, but lately the method we came to use is live imaging. So, we are trying and willing to look with longitudinal imaging at all those pathological events to have a clearer perspective of the times and so on. Because to work on fixed time points is not bringing all the dynamic ideas that occur in the brain. The brain is a complex organ with multiple different cell types and so on that interact one with the other. In pathological conditions, you have all these inflammatory bursts that arrive also at the site which make it too complicated to study with just fixed-time samples. You really need to have this idea of dynamics.

Dr. Alvarez: And you recently started using one of our Leica systems, an SP8 DIVE which is a multiphoton system and how has this helped you or changed the way that you approach brain imaging?

Dr. Mathivet: It completely changed the approach clearly. So, I used to work in my previous lab with another solution from Leica which was implicating to change filters. So basically, we were restricted to the filters and with all the new models we are working on, which need five or six different channels for visualization all at the same time, using filters was no longer a solution. We could not image all this information together, which was really a pity. The DIVE system with the 4TUNE really change radically what we could see. Basically, we can narrow the windows to 10 to 20 nanometers with those tunable detectors which is fantastic to imagine looking at, for example, the Brainbow mouse where you will have a GFP, YFP, RFP, and CFP. All that you can perfectly divide up in the picture without having to do the classical linear mixing we were using in the past and this kind of things. Also, the other nice information for a vascular biologist is to be able to look at collagen fibers for all the structural aspect of the brain. So, we can look at the vessels, but also the collagen at the pia surface or the surface of the meninges. We can look at that with the SHG second harmonic perfectly, because of narrowing this window just on your detection window and that’s fabulous. Other information that we can get for free in a completely ready-to-use system. So that’s what I would say. DIVE really changed this approach of multiple things we could see, multiple information we could get at the same time and compatible with in vivo longitudinal imaging. Because the other problem is that in the past we would have to do multiple sequences to detect all that which is not compatible with an animal moving, an animal living, biological process where the time resolution is seconds not minutes and now we can get there with the DIVE system.

Dr. Alvarez: Thank you for sharing these thoughts and we hope that we can accompany you with this new research and try to see where we can go next.

Dr. Mathivet: Thank you, that is gladly appreciated.