title: 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.
abstract: Inflammation may play a role in the development of epilepsy after brain insults. [11C]-( R)-PK11195 binds to TSPO, expressed by activated microglia. We quantified [11C]-( 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. [11C]-( R)-PK11195 PET binding and MR biomarker changes could be detected with only nine rats, highlighting the potential of longitudinal imaging studies.
authors.affiliation: 1 Neurodis Foundation, Lyon, France.
authors.forename: J
authors.initials: J
authors.lastname: Yankam Njiwa
authors.affiliation: 2 CERMEP-Imagerie du Vivant, Lyon, France.
authors.forename: N
authors.initials: N
authors.lastname: Costes
authors.affiliation: 2 CERMEP-Imagerie du Vivant, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Bouillot
authors.affiliation: 2 CERMEP-Imagerie du Vivant, Lyon, France.|3 Lyon Neuroscience Research Center, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Bouvard
authors.affiliation: 2 CERMEP-Imagerie du Vivant, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Fieux
authors.affiliation: 2 CERMEP-Imagerie du Vivant, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Becker
authors.affiliation: 3 Lyon Neuroscience Research Center, University Claude Bernard Lyon 1, Lyon, France.|4 Hospices Civils de Lyon, France.
authors.forename: E
authors.initials: E
authors.lastname: Levigoureux
authors.affiliation: 5 CREATIS, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Kocevar
authors.affiliation: 5 CREATIS, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Stamile
authors.affiliation: 2 CERMEP-Imagerie du Vivant, Lyon, France.
authors.forename: J B
authors.initials: JB
authors.lastname: Langlois
authors.affiliation: 3 Lyon Neuroscience Research Center, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: R
authors.initials: R
authors.lastname: Bolbos
authors.affiliation: 3 Lyon Neuroscience Research Center, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Bonnet
authors.affiliation: 3 Lyon Neuroscience Research Center, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: L
authors.initials: L
authors.lastname: Bezin
authors.affiliation: 2 CERMEP-Imagerie du Vivant, Lyon, France.|3 Lyon Neuroscience Research Center, University Claude Bernard Lyon 1, Lyon, France.|4 Hospices Civils de Lyon, France.
authors.forename: L
authors.initials: L
authors.lastname: Zimmer
authors.affiliation: 1 Neurodis Foundation, Lyon, France.|6 Division of Imaging Sciences and Biomedical Engineering, King's College London & Guy's and St Thomas' PET Centre, King's College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Hammers
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000276:immunology* / Q000378:metabolism; D007546:Isoquinolines; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D010862:Pilocarpine; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D007546:Isoquinolines; D011963:Receptors, GABA-A; D010862:Pilocarpine; C069997:Tspo protein, rat; C037850:PK 11195
keywords: Epileptogenesis; TSPO; neuroinflammation; pilocarpine; status epilepticus