Quantitative longitudinal imaging of activated microglia as a marker of inflammation in the pilocarpine rat model of epilepsy using [ 11 C]-( R )-PK11195 PET and MRI

J. Yankam-Njiwa (1) , N. Costes (2) , C. Bouillot (2) , S. Bouvard (3, 2) , S. Fieux (2) , G. Becker (2) , E. Levigoureux (3) , G. Kocevar (4) , C. Stamile (4) , J.-B. Langlois (2) , R. Bolbos (3) , C. Bonnet (3) , L. Bezin (3) , L. Zimmer (2, 3, 5) , A Hammers (1, 6)

1 Fondation neurodis
2 CERMEP - imagerie du vivant - Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant
3 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
4 RMN et optique : De la mesure au biomarqueur
5 HCL - Hospices Civils de Lyon
6 Division of Experimental Medicine

Inflammation may play a role in the development of epilepsy after brain insults. [ 11 C]-(R)-PK11195 binds to TSPO, expressed by activated microglia. We quantified [ 11 C]-(R)-PK11195 binding during epileptogenesis after pilocarpine-induced status epilepticus (SE), a model of temporal lobe epilepsy. Nine male rats were studied thrice (D0-1, D0 þ 6, D0 þ 35, D0 ¼ SE induction). In the same session, 7T T2-weighted images and DTI for mean diffusivity (MD) and fractional anisotropy (FA) maps were acquired, followed by dynamic PET/ CT. On D0 þ 35, femoral arterial blood was sampled for rat-specific metabolite-corrected arterial plasma input functions (AIFs). In multiple MR-derived ROIs, we assessed four kinetic models (two with AIFs; two using a reference region), standard uptake values (SUVs), and a model with a mean AIF. All models showed large (up to twofold) and significant TSPO binding increases in regions expected to be affected, and comparatively little change in the brainstem, at D0 þ 6. Some individuals showed increases at D0 þ 35. AIF models yielded more consistent increases at D0 þ 6. FA values were decreased at D0 þ 6 and had recovered by D0 þ 35. MD was increased at D0 þ 6 and more so at D0 þ 35. [ 11 C]-(R)-PK11195 PET binding and MR biomarker changes could be detected with only nine rats, highlighting the potential of longitudinal imaging studies.

Mots clés: TSPO; status epilepticus; Epileptogenesis; pilocarpine; neuroinflammation

Domaines: Imagerie

J. Yankam-Njiwa, N. Costes, C. Bouillot, S. Bouvard, S. Fieux, et al.. Quantitative longitudinal imaging of activated microglia as a marker of inflammation in the pilocarpine rat model of epilepsy using [ 11 C]-( R )-PK11195 PET and MRI. Journal of Cerebral Blood Flow and Metabolism, 2017, 37 (4), pp.1251 - 1263. ⟨10.1177/0271678X16653615⟩. ⟨hal-01571316⟩