title: Quantitative Assessment of MRI T2 Response to Kainic Acid Neurotoxicity in Rats in vivo.
abstract: The aim of this study was to assess quantitative changes in T2 relaxation using magnetic resonance imaging approaches in rats exposed to kainic acid to assess the utility of such endpoints as biomarkers of neurotoxicity. Quantitative T2 mapping was performed in 21 rats before and 2, 24, and 48 h after a single ip injection of 10 mg/kg of kainic acid. Three methods of quantifying T2 changes were explored: (1) Thresholding: all voxels exhibiting T2 ≤ 72 ms were designated normal tissue, whereas voxels exhibiting T2 > 72 ms were designated as lesioned tissue; (2) Statistical mapping: T2 maps obtained after treatment were statistically compared with averaged "baseline" maps, voxel-by-voxel; (3) Within-subject difference from baseline: for each individual the baseline T2 map was subtracted from the T2 map obtained after treatment. Based on the follow-up histopathological response there were 9 responders, 7 nonresponders, and 5 animals were not classified due to early sacrifice at 2 h which was too soon after treatment to detect any morphological evidence. The "thresholding" method (1) detected differences between groups only at the later time point of 48 h, the "statistical mapping" approach (2) detected differences 24 and 48 h after treatment, and the "within-subject difference from baseline" method (3) detected statistically significant differences between groups at each time point (2, 24, and 48 h). T2 mapping provides an easily quantifiable biomarker and the quantification method employing the use of the same animal as its own control provides the most sensitive metrics.
authors.affiliation: *Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas and Office of Testing and Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland Serguei.liachenko@fda.hhs.gov.
authors.forename: Serguei
authors.initials: S
authors.lastname: Liachenko
authors.affiliation: *Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas and Office of Testing and Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Jaivijay
authors.initials: J
authors.lastname: Ramu
authors.affiliation: *Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas and Office of Testing and Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Konak
authors.affiliation: *Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas and Office of Testing and Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.affiliation: *Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas and Office of Testing and Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hanig
mesh_terms: D000818:Animals; D007608:Kainic Acid / Q000633:toxicity*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009420:Nervous System / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007608:Kainic Acid
keywords: MRI; T2 map; brain; kainic acid; quantification; rat; registration; toxicity