title: In vivo magnetization transfer MRI shows dysmyelination in an ischemic mouse model of periventricular leukomalacia.
abstract: Periventricular leukomalacia, PVL, is the leading cause of cerebral palsy in prematurely born infants, and therefore more effective interventions are required. The objective of this study was to develop an ischemic injury model of PVL in mice and to determine the feasibility of in vivo magnetization transfer (MT) magnetic resonance imaging (MRI) as a potential monitoring tool for the evaluation of disease severity and experimental therapeutics. Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal day 5 (P5); at P60, in vivo T2-weighted (T2w) and MT-MRI were performed and correlated with postmortem histopathology. In vivo T2w MRI showed thinning of the right corpus callosum, but no significant changes in hippocampal and hemispheric volumes. Magnetization transfer MRI revealed significant white matter abnormalities in the bilateral corpus callosum and internal capsule. These quantitative MT-MRI changes correlated highly with postmortem findings of reduced myelin basic protein in bilateral white matter tracts. Ventriculomegaly and persistent astrogliosis were observed on the ligated side, along with evidence of axonopathy and fewer oligodendrocytes in the corpus callosum. We present an ischemia-induced mouse model of PVL, which has pathologic abnormalities resembling autopsy reports in infants with PVL. We further validate in vivo MRI techniques as quantitative monitoring tools that highly correlate with postmortem histopathology.
authors.affiliation: Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland 21205, USA. fatemi@kennedykrieger.org
authors.forename: Ali
authors.initials: A
authors.lastname: Fatemi
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Wilson
authors.forename: Andre W
authors.initials: AW
authors.lastname: Phillips
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMahon
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Zhang
authors.forename: Seth A
authors.initials: SA
authors.lastname: Smith
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Arauz
authors.forename: Sina
authors.initials: S
authors.lastname: Falahati
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Gummadavelli
authors.forename: Hima
authors.initials: H
authors.lastname: Bodagala
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.forename: Michael V
authors.initials: MV
authors.lastname: Johnston
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002547:Cerebral Palsy / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003337:Corpus Callosum / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007969:Leukomalacia, Periventricular / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D011859:Radiography; D013997:Time Factors
chemical_list: D004676:Myelin Basic Protein