title: Network evolution in mesial temporal lobe epilepsy revealed by diffusion tensor imaging.
abstract: The objective of the present study is to identify novel, time-indexed imaging biomarkers of epileptogenesis in mesial temporal lobe epilepsy (MTLE).
  
  
  
  We used high-resolution brain diffusion tensor imaging (DTI) of the translationally relevant methionine sulfoximine (MSO) brain infusion model of MTLE. MSO inhibits astroglial glutamine synthetase, which is deficient in the epileptogenic hippocampal formation of patients with MTLE. MSO-infused (epileptogenic) rats were compared with phosphate-buffered saline (PBS)-infused (nonepileptogenic) rats at early (3-4 days) and late (6-9 weeks) time points during epileptogenesis.
  
  
  
  The epileptogenic rats exhibited significant changes in DTI-measured fractional anisotropy (FA) in numerous brain regions versus nonepileptogenic rats. Changes included decreases and increases in FA in regions such as the entorhinal-hippocampal area, amygdala, corpus callosum, thalamus, striatum, accumbens, and neocortex. The FA changes evolved over time as animals transitioned from early to late epileptogenesis. For example, some areas with significant decreases in FA early in epileptogenesis changed to significant increases late in epileptogenesis. Finally, the FA changes significantly correlated with the seizure load.
  
  
  
  Our results suggest (1) that high-resolution DTI can be used for early identification and tracking of the epileptogenic process in MTLE, and (2) that the process identified by DTI is present in multiple brain areas, even though infusion of MSO is restricted to the unilateral entorhinal-hippocampal region.
authors.affiliation: Department of Laboratory Medicine, Yale University, New Haven, CT, U.S.A.
authors.forename: Helen
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, U.S.A.
authors.forename: Yuegao
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, U.S.A.
authors.forename: Daniel
authors.initials: D
authors.lastname: Coman
authors.affiliation: School of Informatics, Informatics Forum, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Reshma
authors.initials: R
authors.lastname: Munbodh
authors.affiliation: Department of Laboratory Medicine, Yale University, New Haven, CT, U.S.A.
authors.forename: Roni
authors.initials: R
authors.lastname: Dhaher
authors.affiliation: Department of Neurology, Yale University, New Haven, CT, U.S.A.
authors.forename: Hitten P
authors.initials: HP
authors.lastname: Zaveri
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, U.S.A.|Department of Biomedical Engineering, Yale University, New Haven, CT, U.S.A.
authors.forename: Fahmeed
authors.initials: F
authors.lastname: Hyder
authors.affiliation: Department of Laboratory Medicine, Yale University, New Haven, CT, U.S.A.
authors.forename: Tore
authors.initials: T
authors.lastname: Eid
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000503:physiopathology; D007089:Image Enhancement; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D008717:Methionine Sulfoximine; D009415:Nerve Net / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D008717:Methionine Sulfoximine; D005974:Glutamate-Ammonia Ligase
keywords: Animal models; Astrocyte; Epileptogenesis; Glutamine synthetase