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Biography
I received my Master degree in Physics and my Ph.D in Biomedical Engineering from the University Claude Bernard Lyon 1 (Lyon, France) in 2000. I then worked at the Center for Pharmaceutical and Molecular Imaging (CPMI), San Francisco (UCSF), as a post-doctoral fellow. Since 2002, I have been working in the Brain Imaging team of the Creatis lab (UMR CNRS 5220, U1044 Inserm) as a CNRS research associate.
My research thematics focus on the development of in-vivo molecular imaging methods using innovative contrast agents and multimodal approaches for translational research in neurology and stroke in particular.
• MRI of inflammation using iron oxide nanoparticles:
My main achievement is the development of an innovative MRI and X-ray method devoted to the analysis of neuroinflammation following ischemic stroke. This imaging method is based on the in-vivo magnetic labelling of phagocytic cells with ultrasmall superparamagnetic particles of iron oxide (USPIOs). I have shown that MR-tracking of macrophages was feasible in mice with this method (1,2) and that it allowed to monitor of anti-inflammatory treatments (3,4). In parallel, I teamed with the head of Lyon’s stroke unit, Pr Nighoghossian, to translate the method into the clinics (5,6). My current motivations are to improve the specificity of the approach by targeting a macrophage receptor, Mac-1, and to further validate the MRI endpoints by taking advantage of multimodality opportunities, such as two-photon microscopy, phase-contrast microtomography using Synchrotron Radiation at the European Synchrotron Radiation Facility (ESRF) (7,8), k-edge imaging with spectral scanner, PET and hybrid PET/MR technology.
• MRI monitoring of neuroprotection treatments of ischemic stroke:
I have developed a translational platform for investigating rodent models of ischemic stroke at Lyon's imaging platform Cermep. All experiments follow the STAIR guidelines (9). In brief, sample size are calculated for each protocol based on the planned methodology (usually repeated measures analysis of variance), the expected difference between groups, the expected variance and a statistical power of 80%. Allocation to experimental groups are randomized. All investigators are blinded to group allocation. The originality of my approach is to use MRI for animal inclusion and follow-up (10-13). I have implemented the same sequences as in clinical trials and I am currently working towards the identification of translational imaging endpoints.
• Quantification of tissue perfusion and capillary permeability with MRI:
My main contribution to the field is the development of methodological tools, based on black-box analysis or compartmental modelling, to extract quantitative hemodynamic parameters from the kinetics of an MR contrast agent. These works had broad applications both in the pre-clinical and in the clinical arenas: carotid stenosis (14), stroke (15-17), myocardial infarction (18,19), pulmonary embolism (20), breast cancer (21), prostate cancer (22) and liver cancer (23).
References:
1. Desestret V, Brisset JC, Moucharrafie S, Devillard E, Nataf S, Honnorat J, Nighoghossian N, Berthezene Y, Wiart M. Early-stage investigations of ultrasmall superparamagnetic iron oxide-induced signal change after permanent middle cerebral artery occlusion in mice. Stroke 2009;40(5):1834-1841.
2. Wiart M, Davoust N, Pialat JB, Desestret V, Moucharaffie S, Cho TH, Mutin M, Langlois JB, Beuf O, Honnorat J, Nighoghossian N, Berthezene Y. MRI monitoring of neuroinflammation in mouse focal ischemia. Stroke 2007;38(1):131-137.
3. Desestret V, Riou A, Chauveau F, Cho TH, Devillard E, Marinescu M, Ferrera R, Rey C, Chanal M, Angoulvant D, Honnorat J, Nighoghossian N, Berthezene Y, Nataf S, Wiart M. In vitro and in vivo models of cerebral ischemia show discrepancy in therapeutic effects of M2 macrophages. PloS one 2013;8(6):e67063.
4. Marinescu M, Chauveau F, Durand A, Riou A, Cho TH, Dencausse A, Ballet S, Nighoghossian N, Berthezene Y, Wiart M. Monitoring therapeutic effects in experimental stroke by serial USPIO-enhanced MRI. Eur Radiol 2013;23(1):37-47.
5. Cho TH, Nighoghossian N, Wiart M, Desestret V, Cakmak S, Berthezene Y, Derex L, Louis-Tisserand G, Honnorat J, Froment JC, Hermier M. USPIO-enhanced MRI of neuroinflammation at the sub-acute stage of ischemic stroke: preliminary data. Cerebrovascular diseases (Basel, Switzerland) 2007;24(6):544-546.
6. Nighoghossian N, Wiart M, Cakmak S, Berthezene Y, Derex L, Cho TH, Nemoz C, Chapuis F, Tisserand GL, Pialat JB, Trouillas P, Froment JC, Hermier M. Inflammatory response after ischemic stroke: a USPIO-enhanced MRI study in patients. Stroke 2007;38(2):303-307.
7. Marinescu M, Langer M, Durand A, Olivier C, Chabrol A, Rositi H, Chauveau F, Cho TH, Nighoghossian N, Berthezene Y, Peyrin F, Wiart M. Synchrotron Radiation X-Ray Phase Micro-computed Tomography as a New Method to Detect Iron Oxide Nanoparticles in the Brain. Mol Imaging Biol 2013;15(5):552-559.
8. Rositi H, Frindel C, Langer M, Wiart M, Olivier C, Peyrin F, Rousseau D. Information-based analysis of X-ray in-line phase tomography with application to the detection of iron oxide nanoparticles in the brain. Optics express 2013;21(22):27185-27196.
9. Fisher M, Feuerstein G, Howells DW, Hurn PD, Kent TA, Savitz SI, Lo EH. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 2009;40(6):2244-2250.
10. Chauveau F, Cho TH, Riou A, Langlois JB, Berthezene Y, Nighoghossian N, Wiart M. Does acute behavioral testing reflect successful ischemia in rats with transient middle cerebral artery occlusion? Int J Stroke 2011;7(6):465-472.
11. Chauveau F, Marinescu M, Cho TH, Wiart M, Berthezene Y, Nighoghossian N. MRI assessment of post-ischemic neuroinflammation and neuroprotection in ischemic stroke models and prediction of stroke severity in patients. In: Intech, editor. Neuroimaging - methods; 2012.
12. Cho TH, Aguettaz P, Campuzano Larrea O, Charriaut-Marlangue C, Riou A, Berthezene Y, Nighoghossian N, Ovize M, Wiart M, Chauveau F. Pre- and post-treatment with cyclosporine A in a rat model of transient focal cerebral ischaemia with multimodal MRI screening. Int J Stroke 2013;8(8):669-674.
13. Durand A, Chauveau F, Cho TH, Bolbos R, Langlois JB, Hermitte L, Wiart M, Berthezene Y, Nighoghossian N. Spontaneous reperfusion after in situ thromboembolic stroke in mice. PloS one 2013;7(11):e50083.
14. Wiart M, Berthezene Y, Adeleine P, Feugier P, Trouillas P, Froment JC, Nighoghossian N. Vasodilatory response of border zones to acetazolamide before and after endarterectomy : an echo planar imaging-dynamic susceptibility contrast-enhanced MRI study in patients with high-grade unilateral internal carotid artery stenosis. Stroke 2000;31(7):1561-1565.
15. Hermier M, Nighoghossian N, Derex L, Wiart M, Nemoz C, Berthezene Y, Froment JC. Hypointense leptomeningeal vessels at T2*-weighted MRI in acute ischemic stroke. Neurology 2005;65(4):652-653.
16. Pialat JB, Wiart M, Nighoghossian N, Adeleine P, Derex L, Hermier M, Froment JC, Berthezene Y. Evolution of lesion volume in acute stroke treated by intravenous t-PA. J Magn Reson Imaging 2005;22(1):23-28.
17. Ritzenthaler T, Cho TH, Wiart M, Berthiller J, Ostergaard L, Hermier M, Derex L, Berthezene Y, Nighoghossian N. Assessment of baseline hemodynamic parameters within infarct progression areas in acute stroke patients using perfusion-weighted MRI. Neuroradiology 2011;53(8):571-576.
18. Carme S, Mai W, Mazzadi A, Janier M, Revel D, Magnin I, Wiart M, Neyran B, Canet-Soulas E. Importance of parametric mapping and deconvolution in analyzing magnetic resonance myocardial perfusion images. Invest Radiol 2006;41(4):374-383.
19. Wiart M, Carme S, Mai W, Larsson HB, Neyran B, Canet-Soulas E. In vivo quantification of regional myocardial blood flow: validity of the fast-exchange approximation for intravascular T1 contrast agent and long inversion time. Magn Reson Med 2006;56(2):340-347.
20. Viallon M, Berthezene Y, Decorps M, Wiart M, Callot V, Bourgeois M, Humblot H, Briguet A, Cremillieux Y. Laser-polarized (3)He as a probe for dynamic regional measurements of lung perfusion and ventilation using magnetic resonance imaging. Magn Reson Med 2000;44(1):1-4.
21. Wiart M, Fournier LS, Novikov VY, Shames DM, Roberts TP, Fu Y, Shalinsky DR, Brasch RC. Magnetic resonance imaging detects early changes in microvascular permeability in xenograft tumors after treatment with the matrix metalloprotease inhibitor prinomastat. Technol Cancer Res Treat 2004;3(4):377-382.
22. Wiart M, Curiel L, Gelet A, Lyonnet D, Chapelon JY, Rouviere O. Influence of perfusion on high-intensity focused ultrasound prostate ablation: A first-pass MRI study. Magn Reson Med 2007;58(1):119-127.
23. Abdullah SS, Pialat JB, Wiart M, Duboeuf F, Mabrut JY, Bancel B, Rode A, Ducerf C, Baulieux J, Berthezene Y. Characterization of hepatocellular carcinoma and colorectal liver metastasis by means of perfusion MRI. J Magn Reson Imaging 2008;28(2):390-395.
Key words: Magnetic resonance imaging, molecular imaging, contrast agents, nanoparticles, stroke, inflammation
Documents
Early achievements track-record
Habilitation à diriger des Recherches (HDR, in French)
