Quantitative longitudinal imaging of activated microglia as a marker of inflammation in the pilocarpine rat model of epilepsy using [11C]-(R)-PK11195 PET and MRI. Issue 4 (April 2017)

• Record Type: Journal Article
• Authors: Yankam Njiwa, J; Costes, N; Bouillot, C; Bouvard, S; Fieux, S; Becker, G; Levigoureux, E; Kocevar, G; Stamile, C; Langlois, JB; Bolbos, R; Bonnet, C; Bezin, L; Zimmer, L; Hammers, A
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 37:Issue 4(2017)
• Page Start: 1251
• Page End: 1263
• Publication Date: 2017-04
• Subjects: Epileptogenesis -- TSPO -- neuroinflammation -- pilocarpine -- status epilepticus; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X16653615
• Languages: English
• ISSNs: 0271-678X

Abstract

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 + 6, D0 + 35, D0 = 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 + 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 two-fold) and significant TSPO binding increases in regions expected to be affected, and comparatively little change in the brainstem, at D0 + 6. Some individuals showed increases at D0 + 35. AIF models yielded more consistent increases at D0 + 6. FA values were decreased at D0 + 6 and had recovered by D0 + 35. MD was increased at D0 + 6 and more so at D0 + 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.