title: Diffusion tensor MRI shows progressive changes in the hippocampus and dentate gyrus after status epilepticus in rat - histological validation with Fourier-based analysis.
abstract: Imaging markers for monitoring disease progression, recovery, and treatment efficacy are a major unmet need for many neurological diseases, including epilepsy. Recent evidence suggests that diffusion tensor imaging (DTI) provides high microstructural contrast even outside major white matter tracts. We hypothesized that in vivo DTI could detect progressive microstructural changes in the dentate gyrus and the hippocampal CA3bc in the rat brain after status epilepticus (SE). To test this hypothesis, we induced SE with systemic kainic acid or pilocarpine in adult male Wistar rats and subsequently scanned them using in vivo DTI at five time-points: prior to SE, and 10, 20, 34, and 79 days post SE. In order to tie the DTI findings to changes in the tissue microstructure, myelin- and glial fibrillary acidic protein (GFAP)-stained sections from the same animals underwent Fourier analysis. We compared the Fourier analysis parameters, anisotropy index and angle of myelinated axons or astrocyte processes, to corresponding DTI parameters, fractional anisotropy (FA) and the orientation angle of the principal eigenvector. We found progressive detectable changes in DTI parameters in both the dentate gyrus (FA, axial diffusivity [D||], linear anisotropy [CL] and spherical anisotropy [CS], p<0.001, linear mixed-effects model [LMEM]) and the CA3bc (FA, D||, CS, and angle, p<0.001, LMEM; CL and planar anisotropy [CP], p<0.01, LMEM) post SE. The Fourier analysis revealed that both myelinated axons and astrocyte processes played a role in the water diffusion anisotropy changes detected by DTI in individual portions of the dentate gyrus (suprapyramidal blade, mid-portion, and infrapyramidal blade). In the whole dentate gyrus, myelinated axons markedly contributed to the water diffusion changes. In CA3bc as well as in CA3b and CA3c, both myelinated axons and astrocyte processes contributed to water diffusion anisotropy and orientation. Our study revealed that DTI is a promising method for noninvasive detection of microstructural alterations in the hippocampus proper. These alterations may be potential imaging markers for epileptogenesis.
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Raimo A
authors.initials: RA
authors.lastname: Salo
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Tuukka
authors.initials: T
authors.lastname: Miettinen
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Laitinen
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Gröhn
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland. Electronic address: alejandra.sierralopez@uef.fi.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Sierra
mesh_terms: D000818:Animals; D016880:Anisotropy; D001253:Astrocytes / Q000473:pathology; D001931:Brain Mapping / Q000379:methods*; D018891:Dentate Gyrus / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005583:Fourier Analysis; D007608:Kainic Acid / Q000008:administration & dosage; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology*
chemical_list: D007608:Kainic Acid