Preclinical MRI investigations of neurological diseases, biomarkers and therapeutics

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The “Preclinical MRI investigations of neurological diseases, biomarkers and therapeutics” team aims at investigating imaging strategies and translational approaches in experimental models. Imaging biomarkers are crucial for the diagnosis and for the longitudinal follow up of disease and therapeutics.

Translational approaches aim at using the same imaging and processing tools in animal models as in clinical research settings.

The team develops in vivo and post-mortem magnetic resonance imaging (MRI) protocols at very high magnetic field (11.7T) for the evaluation of rodent and small primate models of movement disorders such as Parkinson’s disease. It requires a comprehensive approach from animal models, to imaging and to histological validations.

The main developments of the team are:

(1) Translational MRI markers of neurodegeneration and neuroinflammation

(2) Vectorized contrast agents delivered through ultrasound-mediated blood-brain-barrier opening for MRI detection and follow up of diagnostic and therapeutic drugs into the brain for translational applications

(3) Therapeutic evaluations in animal models

Equipment

The ICM 11.7T facility includes the entire pipeline for preclinical studies: data acquisition, post-processing and data analysis as well as animal handling and biological support.

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- 11.7T MRI system (Biospec Avance 117/16 USR, AVIII, Gradients BGA9-S, Paravision 6)

- Animal support (anesthesia, physiological monitoring, cradles)

- Proton radio-frequency coils (resonator for rat head / mouse whole body in transmit /receive 38 mm, transmit resonator 72 mm, mouse head surface coil)

- Other nuclei radiofrequency coils (surface transmit/receive 1H/13C 20 mm, surface 1H/31P 20 mm)

- Cryoprobe (Bruker)

- Focused ultrasound system combined to the MRI system

Staff and CENIR collaborators

Stéphane Lehéricy, MD-PhD, head of CENIR

Mathieu Santin, PhD, MR and ultrasound physicist

Laura Mouton, PhD, post-doctoral fellow

Francesca Branzoli, PhD

Romain Valabrègue, PhD

Eric Bardinet, PhD

Lydia Yahia-Cherif, PhD

Benoit Béranger, Engineer

1. Ahmed M, Hernández-Verdin I, Quissac E, Lemaire N, Guerin CL, GuyonnetL, Zahr N, Mouton L, Santin M, Petiet A, Schmitt C, Bouchoux G, CanneyM, Sanson M, Verreault M, Carpentier A, Idbaih A, “Low-intensity pulsed ultrasound-mediated blood-brain barrier opening increases anti-programmed death-ligand 1 delivery and efficacy in glioblastoma mouse models”, submitted 2021.

2. PetietA. Current and Emerging MR Methods and Outcome in Rodent Models of Parkinson's Disease: A Review. Front. Neurosci. 2021 Apr 7;15:583678. doi:10.3389/fnins.2021.583678.

3. Genovese G, Palombo M,Santin MD, Valette J, Ligneul C, Aigrot MS, Abdoulkader N, Langui D, MillecampsA, Baron-Van Evercooren A, Stankoff B, Lehericy S, Petiet A*,Branzoli F*. Inflammation-driven glial alterations in the cuprizone mouse model probed with diffusion-weighted magnetic resonance spectroscopy at11.7 T. NRM Biomed. 2021 Apr;34(4):e4480. doi:10.1002/nbm.4480. *Equal contribution

4. Hill I, Palombo M, Santin M, Branzoli F, PhilippeA-C, Wassermann D, Aigrot M-S, Stankoff B, Baron-VanEvercooren A, Felfi M,Langui D, Zhang H, Lehéricy S, Petiet A, Alexander DC, Ciccarelli O, DrobnjakI. Machine learning based white matter models with permeability: An experimental study in cuprizone treated in-vivo mouse model of axonal demyelination. Machine learning based white matter models with permeability : an experimental study in cuprizone treated in-vivo mouse model of axonal demyelination. Neuroimage 2020. https://doi.org/10.1016/j.neuroimage.2020.117425

5. Petiet A, Adanyeguh I, Aigrot MS,Poirion E, Nait-Oumesmar B, Santin M, Stankoff B. Ultrahigh field imaging of myelin disease models: Toward specific markers of myelin integrity? J Comp Neurol. 2019 Sep 1;527(13):2179-2189. doi: 10.1002/cne.24598. Review.

6. Androuin A, Abada YS, Ly M, Santin M, Petiet A, Epelbaum S, Bertrand A,Delatour B. Activity-induced MEMRI cannot detect functional brain anomalies in the APPxPS1-Ki mouse model of Alzheimer's disease. Sci Rep. 2019 Feb 4;9(1):1140. doi:10.1038/s41598-018-37980-y.

7. FilipiakP, Fick R, Petiet A, Santin M,Philippe AC, Lehericy S, Ciuciu P, Deriche R, Wassermann D. Reducing the number of samples in spatiotemporal dMRI acquisition design. Magn Reson Med. 2019May;81(5):3218-3233. doi: 10.1002/mrm.27601.

8. Rebagliati M., Vilhais-Neto GC., Petiet A., Lange M., Michaut A.,Plassat JL., Vermot J., Riet F., Noblet V., Brasse D., Laquerrière P., CussighD., Bedu S., Dray N., Gomaa MS., Simons C., Meziane H., Lehéricy S., Bally-CuifL., Pourquié O. Rere-dependent Retinoic Acid signaling controls brain asymmetry and handedness. BioRxiv Mar 15, 2019.doi:http://dx.doi.org/10.1101/578625.

9. PerlbargV, Lambert J, Butler B, Felfli M, Valabrègue R, Privat AL, Lehéricy S, Petiet A. Alterations of the nigrostriatal pathway in a 6-OHDA rat model of Parkinson's disease evaluated with multimodal MRI. PLoS One 2018 Sep 6;13(9):e0202597. doi: 10.1371/journal.pone.0202597.eCollection 2018.

10. Rutger H.J. Fick, Alexandra Petiet, Mathieu Santin,Anne-Charlotte Philippe, Stephane Lehericy, Rachid Deriche, Demian Wassermann.Non-parametric graphnet-regularized representation of dMRI in space and time, Medical Image Analysis 43 :37-53, 2018. doi:10.1016/j.media.2017.09.002.

11. FilipiakP., Fick RHJ., Petiet A., Santin M.,Philippe AC., Lehéricy S., Deriche R., Wassermann D. Spatio-Temporal dMRI Acquisition Design: Reducing the Number of qτ Samples Through a Relaxed Probabilistic Model. January 2018.DOI:10.1007/978-3-319-73839-0_3. In book: Computational Diffusion MRI.

12. Petiet A, Aigrot MS,Stankoff B. Gray and White Matter Demyelination and Remyelination Detected with Multimodal Quantitative MRI Analysis at 11.7T in a Chronic Mouse Model of Multiple Sclerosis. Front. Neurosci., 27 October 2016. http://dx.doi.org/10.3389/fnins.2016.00491.

13. Vilhais-Neto GC, Fournier M, Petiet A, Plassat JL, Riet F, Noblet V,Laquerrière P, Sardiu ME, Saraf A, Maruhashi M, Garnier JM, Florens L, MezianeH, Washburn MP, Lehéricy S, and Pourquié O, Control of embryo and brain symmetry by the retinoic acid coactivator Rere, in revision.

14. Kundu P, Santin MD, Bandettini PA, Bullmore ET and Petiet A.Differentiating BOLD and non-BOLD signals in 11.7 Tesla Rat Resting State fMRI. NeuroImage 2014. 102:861–874. doi:10.1016/j.neuroimage.2014.07.025.

15. Bertrand A, PasquierA, Petiet A, Wiggins CJ, Kraska A, Joseph-Mathurin N, Aujard F, Mestre-FrancesN and Dhenain M, Micro-MRI study of cerebral aging in mouse lemur primates:detection of hippocampal subfield reorganization, microhemorrhages and amyloid plaques. PlosOne, 8(2):e56593, 2013. doi: 10.1371/journal.pone.0056593.

16. Petiet A, Santin MD, Bertrand A, Wiggins CJ, Petit F,Houitte D, Hantraye P, Benavides J, Debeir T, Rooney T and Dhenain M,Gadolinium-stained brains reveal amyloid plaques in live Alzheimer’s transgenic mice. Neurobiology of Aging, 33:1533-1544,2012. doi:10.1016/j.neurobiolaging.2011.03.009.

17. PetietA, Delatour B, Dhenain M, Models of neurodegenerative disease – Alzheimer’s anatomical and amyloid plaque imaging, In: “In vivo NMR Imaging: Methods and Protocols”, Methods in Molecular Biology, Vol. 771, 2011. doi:10.1007/978-1-61779-219-9_16.

18. PetietA and Dhenain M, Improvement of microscopic MR imaging of amyloid plaques with contrast agents: targeting and non-targeting agents, Current Medical Imaging Review, 7(1):8-15, 2011.

19. PetietAand Johnson GA, Active staining of mouse embryos for magnetic resonance microscopy,Methods in Molecular Biology,611:141-149, 2010. doi:10.1007/978-1-60327-345-9_11.

20. Delatour B, Epelbaum S, Petiet A and DhenainM, In vivo imaging biomarkers in mice models of Alzheimer’s disease: are we lost in translation or breaking through? Int.J.Alz.Dis. 2010:604853, 2010. doi:10.4061/2010/604853.

21. N. Joseph-Mathurin, A. Petiet, P.Hantraye, J.M.Verdier, E.Sigurdsson, N.Mestre-Francés, M.Dhenain, P2b-16 Evaluation in-vivo par IRM des effets toxiques d’une immunothérapie anti-Alzheimer chez le primate microcèbemurin. Revue Neurologique, Oct 2009, Suppl 1,165(10):73-74. DOI: 10.1016/S0035-3787(09)72644-X.

22. A. Pasquier, A. Bertrand, A. Petiet, A. Kraska, C. Wiggins, F. Petit, C. Jan, S. Mériaux, P. Hantraye, F. Aujard, N. Mestre-Francés, M. Dhenain. O2-2 Détection par IRM haute résolution de plaques amyloïdes chez un primate : Le microcèbe. Revue Neurologique, Oct 2009, 165(10):41-42. DOI: 10.1016/S0035-3787(09)72591-3.

23. Petiet AE,Kaufman MH, Goddeeris MM, Brandenburg JL, Elmore SA, Johnson GA,High-resolution magnetic resonance histology of the embryonic and neonatal mouse: a 4D atlas and morphologic database,Proc. Natl. Acad. Sci. USA,105(34):12331-6, 2008. doi:10.1073/pnas.0805747105.

24. DrieyhusB, Nouls J, Badea A, Bucholz L, Ghaghada K, Petiet A and Hedlund L, Small animal imaging with magnetic resonance microscopy, ILAR J,49(1):35-53, 2008.

25. Goddeeris MM, Rho SY, Petiet A, Johnson GA,Klingensmith J and Meyers EN, Intracardiac septation requires hedgehog-dependent cellular contributions from outside the heart, Development,135(10):1887-95, 2008. doi: 10.1242/dev.016147.

26. Petiet A,Hedlund LW, Johnson GA, Staining methods for magnetic resonance microscopy of the developing rat, JMRI,25(6):1192-98, 2007.