"Neuroimaging: Pathophysiology and biomarkers of multiple sclerosis and stroke"
10 décembre 2015
Thomas Tourdias / Affiliations : Service de Neuroimagerie Diagnostique et Thérapeutique, CHU Pellegrin, Bordeaux et INSERM U862 équipe « Relations glie-neurone ». Lieux et horaires : Salle de conférence, Centre de Génomique Fonctionnelle 14h30
Non-invasive in vivo imaging of the brain has revolutionized our understanding and management of brain disorders. Especially magnetic resonance imaging (MRI) has become the “golden” tool to explore the brain. Most of the imaging features derived from MRI can be embedded in the general concept of imaging biomarkers. By definition, an imaging biomarker is an imaging-derived parameter that reflects the presence and the severity of a pathological process. Imaging biomarkers are now among the toolbox of the neuroscientists to (1) better understand the pathophysiology of complex brain disorders. Alternatively, imaging biomarkers are also used by the physicians (2) to manage patients in clinical routine and to power the clinical trials.
PART 1: Understanding the pathophysiology of multiple sclerosis Imaging provides several advantages to address some pathophysiological issues from animal models to humans. Owing to its non-invasive nature, imaging can be repeated to address time course more efficiently than by cross-sectionally sacrificing animals at different time points. The non-invasive nature also provides to imaging a key position for translational research. Indeed, imaging in itself can usually not tackle complete mechanistic issues. Nevertheless, in animals, imaging can be combined with several other methods such as histology, molecular biology or electrophysiology that are usually not available in patients. Then, the imaging markers that reflect cellular and electrical alterations characterized in the animal model can be directly tested in humans using the same imaging methodology as the one used in animals. Finally, imaging can provide quantitative metrics with a sub-millimetric resolution which can be difficult to achieve with other techniques. One example is water content which is very difficult to quantify even in animal models while methods such as diffusion MRI can provide quantitative information related to edema severity and location. The exploration of the whole brain at high spatial resolution can also be viewed as a “screening procedure” to pinpoint relevant locations and then focus the other experiments. Regarding these considerations, I focus one direction of my research in exploring some components of the pathophysiology of brain inflammation especially multiple sclerosis by using imaging methods with a translational approach. In my previous work (PhD in neurosciences obtained in 2011), I used this strategy to better understand acute inflammation in white matter lesions. I have made contributions in understanding the implication of the water channel aquaporin 4 to mitigate the edematous component associated with acute inflammation. I have also been able to track non-invasively the macrophage infiltration in patients with multiple sclerosis thanks to a new contrast agent for MRI (USPIO) in a multicenter European study. During a post-doctoral fellow at Stanford University (CA, USA), I took advantage of one of the few ultra-high field MR system (7Tesla) for human exploration to better understand the unique alteration in grey matter structures during brain inflammation (thalamus and cortical ribbon). I joined the group “glia-neuron interaction” INSERM U862 of Stéphane Oliet in 2013 and I have developed a new project on the same thematic which aims to better understand the pathophysiology of early memory impairment associated with multiple sclerosis. The approach is strongly translational from the animal model to the patients and interdisciplinary from behavior, to histology, to electrophysiology, up to cutting edge in vivo imaging.
PART 2: Validating imaging biomarkers of stroke Imaging biomarkers also play a crucial role in medicine because they can be help to assess an early diagnosis even sometimes before the occurrence of some clinical symptoms. Imaging biomarkers can also provide prognostic information regarding the future course of the disease and the patient outcome. Finally imaging biomarkers can be used to monitor objectively and quantitatively the course of the disease and consequently have been introduced as judgment criteria in therapeutic clinical trials. In phase II trials, by using an imaging metric reflecting the targeted pathological process (surrogate marker), it’s usually possible to gauge the effectiveness of a medical treatment with high sensitivity and in short time frame. Regarding these considerations, I focus another direction of my research in validating imaging biomarker of stroke with a clinical research approach. In my previous work (MD in radiology obtained in 2008) I have made contribution in quantifying stroke damages with imaging to be used as objective judgment criteria in future therapeutics trials. I have now developed a new project on the same thematic which aims at providing early prognostic information with respect to functional and cognitive recovery after stroke. I use a clinical approach with an ongoing large multicenter clinical study (n=350) on stroke patients explored with MRI and followed longitudinally.
Thomas Tourdias MD, PhD / CHU Pellegrin Bordeaux, Inserm U 862 Equipe Relations Glie-Neurone / thomas.tourdias(at)inserm.fr
- Mark Van Buchem, professor of neuroradiology, Leiden University Medical Center ,président
- Jérôme Badaut, Chargé de recherche, CNRS, Bordeaux, Rapporteur
- Alexandre Krainik, professeur des universités praticien hospitalier (PUPH), Grenoble, Rapporteur
- Jérôme de Sèze, professeur des universités praticien hospitalier (PUPH), Strasbourg, Rapporteur
- Vincent Dousset, professeur des universités praticien hospitalier (PUPH), Bordeaux, Examinateur
- Jean François Meder, professeur des universités praticien hospitalier (PUPH), Paris, Examinateur
- Stéphane Oliet, directeur de recherche CNRS, Bordeaux, Examinateur