Head : Caroline FONTA
Images and models for exploring the brain
Our main approach consists in multiscale and multimodal imaging as a basis for developing statistical and modeling tools in order to investigate cerebral physiological and pathological processes.
We are exploring the different brain compartments : vessel and cortical tissue, at the macro and micro-scales in non-human primates and rodent models of Alzheimer’s disease and epilepsy.
We are developing a non-human primate model of the ageing brain pathology combining various imaging techniques : NMR (protocols for brain structure, myelin content, vasculature), PET (glucidic metabolism, amyloid plaques, tau protein, NMDA receptors, inflammation...), XR (microtomography). More specifically, we are exploring in the marmoset monkey (Callithrix jacchus) brain anatomical markers of neurodegenerative diseases (AD) and vascular networks that we combine in order to analyze their relation with the monkey cognitive abilities (collaboration inside Cerco with Florence Rémy (team MAOs) and Pascal Girard (team C3P)).
Each imaging modality deals with one scale, one resolution and one type of information. In addition to image registration, we are investigating multimodal data fusion approaches to combine anatomical and functional data in a joint analysis, and thus uncover both shared and distinct markers of brain aging.
Furthermore, we are contributing to a project initiated at IMFT to simulate cerebral blood flow autoregulation in its cranio-spinal environment. We are investigating CT and MRI-based techniques to identify the topology and geometry of arterial and venous systems in the marmoset brain. Such anatomical data will be used to develop and parameterize a blood flow model for the marmoset in the context of preclinical analysis. The ultimate objectives are a simulator tool and a clinical protocol, using the autoregulation time course pattern to infer the clinical status of the cranio-spinal system and its aging process in humans.
Main external collaborators :
- Pierre Payoux, Anne Sophie Brun-Salabert, Giovanni Mogicato (Tonic INSERM 1214, Toulouse)
- Laurent Risser (Institute of Mathematics, Toulouse)
- Carine Pestourie (Non invasive exploration platform –ENI-, INSERM UMS006, Toulouse)
- Moktar Zagzoule, Patricia Cathalifaud, Franck Plouraboué (Institute of Fluid Mechanics, Toulouse)
- Marcello Rosa (Department of Physiology, Monash University, Australia)
In collaboration with Lionel Nowak (team PAF), we are also developing a research program on adenosine and ectonucleotidases (more specifically the Tissue Non-specific Alkaline Phosphatase –TNAP-) in the cerebral cortex. Adenosine, through its functions in synaptic plasticity and inflammatory processes, is likely to be involved in multiple cerebral pathologies such as epilepsy, Alzheimer disease, and ischemia. To study the sources of adenosine and its role in synaptic transmission, we are developing several approaches : a “metabolomic” approach using TNAP-KO mice, brain slices and neurons in culture treated with inhibitors of ectonucleotidases or overexpressing TNAP, and an electrophysiological approach using brain slices maintained in vitro. A third step will consist in examining the role of adenosine on visual information processing in the marmoset in vivo, in particular the effect of adenosine and A1 receptor antagonists on contrast-gain control, contrast adaptation and gamma-band fluctuations. We are also developing and adapting mathematical models to explore mechanisms of short term plasticity in various conditions (ionic environment, input frequencies).
Main external collaborators
- Véronique Gilard (LSPCMIB, Biomedical NMR group ; University of Toulouse)
- David Magne (ICBMS, University of Lyon)
- Etienne Mornet (Hospital-University Center, Versailles),
- Jose Luis Millan (Burham Institute, La Jolla, CA, USA)
Research interests :
- Ageing brain pathology in non human primate
- Cerebral vascularisation
- Ectonucleotidases and synaptic transmission
brain macro- and microcirculation, brain imaging, multimodal data analysis, mathematical modelling, computational analysis, marmoset monkey, transgenic mice, cerebral cortex, cerebral pathologies, synaptic transmission, adenosine, tissue nonspecific alkaline phosphatase
PhD students :
- Marie GLEIZES (50%)
- Simon PERRIER (50%)
Recent selected publications :
- Caroline Fonta and László Négyessy (Eds) 2015. Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP), Subcellular Biochemistry, Vol. 76. Springer ISBN 978-94-017-7196-2, DOI 10.1007/978-94-017-7197-9. 350pp
- Sadoun A, Strelnikov K, Bonté E, Fonta* C, Girard* P 2015. Cognitive impairment in a young marmoset reveals lateral ventriculomegaly and a mild hippocampal atrophy : a case report. Scientific Reports Nov 3 ;5:16046. doi : 10.1038/srep16046. *equal contribution
- Salabert AS, Fonta C, Fontan C, Adel D, Alonso M, Pestourie C, Belhadj-Tahar H, Tafani M, Payoux P. 2015. Radiolabeling of [18F]-fluoroethylnormemantine and initial in vivo evaluation of this innovative PET tracer for maging the PCP sites of NMDA receptors. Nuclear Medicine and Biology 42 : 643-653
- Risser L, Dolius L, Fonta C, Mescam M. 2014. Diffeomorphic registration with self-adaptive spatial regularization for the segmentation of non-human primate brains. Proceedings of the IEEE Engineering in Medicine and Biology Society. Chicago, USA, August 26-30, 2014 : 6695-6698
- Descombes X, Malandain G, Fonta C, Negyessy L, Mosko R. 2013 Automatic dendrite spines detection from X-Ray tomography volumes. IEEE 10th International Symposium on Biomedical Imaging (ISBI) : from nano to macro. San Francisco, CA, USA, April 7-11, 2013 : 436-439
- Guibert R, Fonta C, Risser L, Plouraboué F 2012. Coupling and robustness of intra-cortical vascular territories. NeuroImage 62:408-417
- Descombes X, Plouraboué F, El Boustani H, Fonta C, LeDuc G, Serduc R, Weitkamp T. 2012. Vascular Network Segmentation : An Unsupervised Approach. IEEE 9th International Symposium on Biomedical Imaging (ISBI), Barcelona, Spain, May 2-5, 2012 : 1248-1251
- Beard DA and Mescam M 2012. Mechanisms of pressure-diuresis ans pressure-natriuresis in Dahl salt-resistant and Dahl salt-sensitive rats. BMC Physiology 12 : 6-19
- Négyessy L, Xiao JS, Kantor O, Kovacs GG, Palkovits M, Doczi TP, Renaud L, Baksa G, Glasz T, Ashaber M, Barone P, Fonta C 2011. Layer-specific activity of Tissue Non-specific Alkaline Phosphatase in the human neocortex. Neuroscience 172 :406-418
- Mescam M, Vinnakota KC, Beard DA 2011. Identification of the catalytic mechanism and estimation of kinetic parameters for fumarase. Journal of Biological Chemistry 286(24) : 21100-21109
- Descombes X, Plouraboué F, El Boustani H, Fonta C, LeDuc G, Serduc R, Weitkamp T. 2011. Brain tumor vascular network segmentation from micro-tomography. IEEE 8th International Symposium on Biomedical Imaging : from nano to macro. Chicago, Ill, USA, March 30- April 2, 2011 : 1113-1116
- Brun-Heath I, Ermoval M, Chabrol E, Xiao JS, Palkovits M, Lyck, R, Miller F, Couraud PO, Mornet E, Fonta C 2011. Differential expression of the bone and the liver Tissue Non-specific Alkaline Phosphatase isoforms in brain tissues. Cell and Tissue Research 343:521-536
- Mescam M, Kretowski M, Bézy-Wendling J 2010. Multiscale model of liver DCE-MRI towards a better understanding of tumor complexity. IEEE Transactions on Medical Imaging 29(3) : 688-698
- Guibert R, Fonta C, Plouraboué F 2010. Cerebral blood flow modeling in primate cortex. Journal of Cerebral Blood Flow and Metabolism 30(11) : 1860-1873
- Risser L, Plouraboué F, Cloetens P, Fonta C 2009. A 3D-investigation shows that angiogenesis in primate cerebral cortex mainly occurs at capillary level. International Journal of Developmental Neuroscience 27:185-196
- Mescam M, Kretowski M, Bézy-Wendling J 2009. Texture-based characterization of arterialization in simulated MRI of hypervascularized liver tumors. Proceedings of the IEEE International Symposium on Biomedical Imaging : From Nano to Macro 93-96