title: Longitudinal diffusion tensor imaging of the rat brain after hexachlorophene exposure.
abstract: Longitudinal MRI employing diffusion tensor imaging and T2mapping approaches has been applied to investigate the mechanisms of white matter damage caused by acute hexachlorophene neurotoxicity in rats in vivo. Male Sprague-Dawley rats were administered hexachlorophene orally once a day for five consecutive days at a dose of 30mg/kg and were monitored in 7T MRI scanner at days 0 (baseline), 3, 6, 13, and 20 following the first hexachlorophene dose. Quantitative T2maps as well as a number of diffusion tensor parameters (fractional anisotropy, radial and axial diffusivity, apparent diffusion coefficient, and trace) were calculated from corresponding MR images. T2, as well as all diffusion tensor derived parameters (except fractional anisotropy) showed significant changes during the course of neurotoxicity development. These changes peaked at 6days after the first dose of hexachlorophene (one day after the last dose) and recovered to practically baseline levels at the end of observation (20days from the first dose). While such changes in diffusivity and T2relaxation clearly demonstrate myelin perturbations consistent with edema, the lack of changes of fractional anisotropy suggests that the structure of the myelin sheath was not disrupted significantly by hexachlorophene in this study. This is also confirmed by the rapid recovery of all observed MRI parameters after cessation of hexachlorophene exposure.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, United States. Electronic address: Jaivijay.Ramu@fda.hhs.gov.
authors.forename: Jaivijay
authors.initials: J
authors.lastname: Ramu
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, United States. Electronic address: Tetyana.Konak@fda.hhs.gov.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Konak
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, United States. Electronic address: Merle.Paule@fda.hhs.gov.
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, White Oak, MD, United States. Electronic address: Joseph.Hanig@fda.hhs.gov.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Hanig
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, United States. Electronic address: Serguei.liachenko@fda.hhs.gov.
authors.forename: Serguei
authors.initials: S
authors.lastname: Liachenko
mesh_terms: D000818:Animals; D016880:Anisotropy; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects*; D056324:Diffusion Tensor Imaging; D006582:Hexachlorophene / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D066127:White Matter / Q000000981:diagnostic imaging / Q000187:drug effects
chemical_list: D000891:Anti-Infective Agents, Local; D006582:Hexachlorophene
keywords: Axial diffusivity; DTI; Fractional anisotropy; Hexachlorophene; Radial diffusivity