title: In vivo detection of cortical abnormalities in BCNU-treated rats, model of cortical dysplasia, using manganese-enhanced magnetic resonance imaging.
abstract: The 1-3-bis-chloroethyl-nitrosurea (BCNU)-treated rats represent a good model of cortical dysplasia (CD), as proved by the presence of some histological alterations similar to those observed in human CD, including cortical thinning, laminar disorganization, and heterotopia. The cortical cytoarchitectonics of BCNU-treated rats has been widely investigated by means of histological procedures, immunocytochemistry, and in situ hybridization techniques, implying the sacrifice of the animals. With the aim of identifying brain alterations in vivo to have the possibility of performing longitudinal studies, we used both conventional T(2)-weighted magnetic resonance imaging (MRI) and manganese-enhanced MRI (MEMRI). Though the T(2)-weighted MRI showed the gross anatomical landmarks of BCNU-treated rats, only following Mn(2+) administration T(1)-weighted MRI did reveal the brain cytoarchitectonics both of control and BCNU-treated rats. In particular, changes in MEMRI signal depicted the laminar architecture of control rats while BCNU-treated cortex showed no appreciable changes in MEMRI contrast, consistent with their abnormal cortical lamination. Furthermore, in the treated animals MEMRI revealed hyperintense signals corresponding to heterotopia, as shown by the comparison between MEMRI images and Thionin staining and calbindin immunocytochemistry from the same animals. The qualitative findings obtained with MEMRI were semi-quantitatively confirmed by image segmentation of grey matter. Overall, these data show that MEMRI can be used as a non-invasive technique to investigate cortical alterations in animal models of CD in vivo, giving the possibility to perform longitudinal studies, such as electrophysiological recordings or behavioural investigations.
authors.affiliation: Clinical Epileptology and Experimental Neurophysiology Unit, Fondazione I.R.C.C.S. Istituto Neurologico "C. Besta", via Celoria 11, 20133 Milan, Italy.
authors.forename: R F
authors.initials: RF
authors.lastname: Moroni
authors.forename: I
authors.initials: I
authors.lastname: Zucca
authors.forename: F
authors.initials: F
authors.lastname: Inverardi
authors.forename: A
authors.initials: A
authors.lastname: Mastropietro
authors.forename: M C
authors.initials: MC
authors.lastname: Regondi
authors.forename: R
authors.initials: R
authors.lastname: Spreafico
authors.forename: C
authors.initials: C
authors.lastname: Frassoni
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D002330:Carmustine / Q000633:toxicity; D004195:Disease Models, Animal; D007089:Image Enhancement / Q000379:methods*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D054220:Malformations of Cortical Development / Q000473:pathology*; D008345:Manganese; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008345:Manganese; D002330:Carmustine