title: The use of MRI to assist the section selections for classical pathology assessment of neurotoxicity.
abstract: MRI was utilized to probe T2 changes in living brain following exposure of rats to one of ten classical neurotoxicants. Brains were subsequently perfused for classical neuropathology examination. This approach was predicated on the assumption that the T2 changes represent loci of neurotoxicity encompassing those seen using neuropathology techniques. The traditional neurotoxicologic approach of selecting a few arbitrary brain sections is dramatically improved by MRI targeting that can indicate the location(s) at which to collect "smart sections" for subsequent workup. MRI scans can provide the equivalent of 64 coronal sections; the number estimated for full coverage of the rat brain if only traditional neuropathology is utilized. Use of MRI allows each animal to serve as its own control as well as longitudinal observations of the life cycle of the neurotoxic lesion(s) (inception, apex and regression). Optimization of time of sacrifice and selection of an appropriate stain based on MRI-identified brain areas could be greatly enhanced should this approach prove successful. The application of full brain MRI imaging that informs neuropathology offers the potential to dramatically improve detection of neurotoxicity produced by new drugs and facilitate new drug development, review and approval processes, and to qualify an imaging biomarker of neuropathology.
authors.affiliation: Food & Drug Administration, Office of Testing & Research, Center for Drug Evaluation and Research, Silver Spring, MD 20993, United States. Electronic address: joseph.hanig@fda.hhs.gov.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hanig
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Jaivijay
authors.initials: J
authors.lastname: Ramu
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Larry
authors.initials: L
authors.lastname: Schmued
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Konak
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Srinivasulu
authors.initials: S
authors.lastname: Chigurupati
authors.affiliation: National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: William
authors.initials: W
authors.lastname: Slikker
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Sumit
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Serguei
authors.initials: S
authors.lastname: Liachenko
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D001931:Brain Mapping; D008279:Magnetic Resonance Imaging; D008297:Male; D020258:Neurotoxicity Syndromes / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D017207:Rats, Sprague-Dawley
chemical_list: D009498:Neurotoxins
keywords: MRI; MRS; Neurotoxicity; T(2) signal