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

• Published in: Journal of cerebral blood flow and metabolism Vol. 37; no. 4; pp. 1251 - 1263
• Main 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
• Format: Journal Article Web Resource
• Language: English
• Published: London, England SAGE Publications 01.04.2017; Nature Publishing Group
• Subjects: Animals; Bioengineering; Brain - diagnostic imaging; Brain - immunology; Brain - metabolism; Carbon Radioisotopes; Carrier Proteins - metabolism; Disease Models, Animal; Epilepsy - diagnostic imaging; Epilepsy - immunology; Epilepsy - metabolism; Human health sciences; Imaging; Isoquinolines; Life Sciences; Longitudinal Studies; Magnetic Resonance Imaging - methods; Male; Microglia - immunology; Microglia - metabolism; Original; Pilocarpine; Positron-Emission Tomography - methods; Protein Binding; Radiologie, médecine & imagerie nucléaire; Radiology, nuclear medicine & imaging; Rats, Sprague-Dawley; Receptors, GABA-A - metabolism; Sciences de la santé humaine; pilocarpine; Epileptogenesis; status epilepticus; TSPO; neuroinflammation
• ISSN: 0271-678X; 1559-7016; 1559-7016
• DOI: 10.1177/0271678X16653615

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.