Application of magnetic resonance imaging in animal models of perinatal hypoxic-ischemic cerebral injury

Departments of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
International Journal of Developmental Neuroscience (Impact Factor: 2.58). 03/2008; 26(1):13-25. DOI: 10.1016/j.ijdevneu.2007.08.018
Source: PubMed


Brain injury occurring in the perinatal period is an important etiology of subsequent neurodevelopmental disabilities. Magnetic resonance imaging (MRI) is a tool that is used to evaluate the nature of brain injury in the human infant. MRI techniques have also been applied to various animal models of perinatal injury. The most commonly used model is the immature rat, but there have also been imaging studies in mice, rabbit kits and piglets. The studies have been carried out using MR systems of various magnetic field strengths, ranging from 1.5 to 11.7tesla (T), with applications for quantification of infarct volume, T1 measurements, T2 measurements, proton and phosphorus spectroscopy and diffusion imaging. The MR findings are then related to histopathology and, in a few cases, behavioral evaluations. There is also a growing number of studies utilizing MRI in evaluating the efficacy of neuroprotective treatments, such as hypothermia.

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    • "n imaging are not related to increas - ing B 0 , but rather to the development of new diffusion models . The apparent diffusion coefficient ( ADC ) has been reported to decrease in the neonatal rodent brain early after HI or inflammation ( Lodygensky et al . , 2008 , 2010 ; Sizonenko et al . , 2007b ) , followed by an increase after several days ( Lodygensky et al . , 2008 , 2010 ; Sizonenko et al . , 2007b ) . The main limitation of ADC relates to the orientation dependence of this coefficient ( i . e . , dependent of the measurement direction ) and the lack of structural information . As such , a more complex model was introduced with diffusion tensor imaging ( DTI ) corresponding to the measurement of "
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    ABSTRACT: Magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) are widely used in the field of brain development and perinatal brain injury. Due to technical progress the magnetic field strength (B0) of MR systems has continuously increased, favoring (1)H-MRS with quantification of up to 18 metabolites in the brain and short echo time (TE) MRI sequences including phase and susceptibility imaging. For longer TE techniques including diffusion imaging modalities, the benefits of higher B0 have not been clearly established. Nevertheless, progress has also been made in new advanced diffusion models that have been developed to enhance the accuracy and specificity of the derived diffusion parameters. In this review, we will describe the latest developments in MRS and MRI techniques, including high-field (1)H-MRS, phase and susceptibility imaging, and diffusion imaging, and discuss their application in the study of cerebral development and perinatal brain injury. Copyright © 2015. Published by Elsevier Ltd.
    International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 03/2015; 45. DOI:10.1016/j.ijdevneu.2015.03.009 · 2.58 Impact Factor
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    • "Functional plasticity in neonatal HI-injured brains It is known that neonatal HI encephalopathy may result in periventricular white matter injury and extensive neuronal loss (Chan et al., 2009b; Lodygensky et al., 2008; Yang et al., 2008). While the interaction of glutamate with its postsynaptic and glial receptors is necessary for the generation of cerebral blood flow and BOLD responses (Canals et al., 2009; Gsell et al., 2006), the smaller BOLD signal increases in both SC of the HI-injured group at P60 than the normal group at P60 in the current study might be a result of glutamate depletion in the injured cerebral white matter (Back et al., 2007) analog to the reduced glutamate uptake in both SC in adulthood upon unilateral neonatal ablation of rat visual cortex (Kvale and Fonnum, 1983). "
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    ABSTRACT: The superior colliculus (SC) is a laminated subcortical structure in the mammalian midbrain, whose superficial layers receive visual information from the retina and the visual cortex. To date, its functional organization and development in the visual system remain largely unknown. This study employed blood oxygenation level-dependent (BOLD) functional MRI to evaluate the visual responses of the SC in normally developing and severe neonatal hypoxic–ischemic (HI)-injured rat brains from the time of eyelid opening to adulthood. MRI was performed to the normal animals (n = 7) at postnatal days (P) 14, 21, 28 and 60. In the HI-injured group (n = 7), the ipsilesional primary and secondary visual cortices were completely damaged after unilateral ligation of the left common carotid artery at P7 followed by hypoxia for 2 h, and MRI was performed at P60. Upon unilateral flash illumination, the normal contralateral SC underwent a systematic increase in BOLD signal amplitude with age especially after the third postnatal week. However, no significant difference in BOLD signal increase was found between P14 and P21. These findings implied the presence of neurovascular coupling at the time of eyelid opening, and the progressive development of hemodynamic regulation in the subcortical visual system. In the HI-injured group at P60, the BOLD signal increases in both SC remained at the same level as the normal group at P28 though they were significantly lower than the normal group at P60. These observations suggested the residual visual functions on both sides of the subcortical brain, despite the damages to the entire ipsilesional visual cortex. The results of this study constitute important evidence on the progressive maturation of visual functions and hemodynamic responses in the normal subcortical brain, and its functional plasticity upon neonatal HI injury.
    NeuroImage 02/2010; 49(3-49):2013-2020. DOI:10.1016/j.neuroimage.2009.10.069 · 6.36 Impact Factor
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    • "In this study, in vivo DTI quantification of full DTI indices was performed onto 7 WM structures of the rat brains at 10 weeks after severe neonatal HI insults at P7. The resulting lesions obtained following an HI episode in postnatal day (P) 7 rats can be considered similar to those observed in the full-term infants who underwent perinatal asphyxia (Balduini et al., 2000; Liu et al., 2002; Skoff et al., 2007; Lodygensky et al., 2008). We demonstrated, for the first time, that this method can improve the detection of long-term effects of brain injury and recovery in neonatal HI insults. "
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    ABSTRACT: Neonatal hypoxic–ischemic encephalopathy is a major cause of brain damage in infants, and is associated with periventricular white matter injury and chronic neurological dysfunctions. However, the mechanisms of the chronic white matter injury and reorganization are still unclear. In this study, in vivo diffusion tensor imaging (DTI) was employed to evaluate the late changes of white matter microstructural integrity in the rat brains at 10 weeks after severe neonatal hypoxic–ischemic insults at postnatal day 7. In the fractional anisotropy directionality map, qualitative evaluation showed that a dorsoventrally oriented fiber bundle extended from the corpus callosum into the cyst in the anterior brain, whilst the posterior peri-infarct areas had similar fiber orientations as the contralateral internal capsule, optic tract and fimbria of hippocampus. Compared to the contralateral hemisphere, significantly higher fractional anisotropy, axial diffusivity and diffusion trace value were observed quantitatively in the distal end of the extended fiber bundle connecting the anterior and posterior white matters rostrocaudally. A significantly lower fractional anisotropy but higher axial and radial diffusivities and trace were also found in the ipsilateral corpus callosum, proximal external capsule and anterior commissure, while slightly lower fractional anisotropy and axial diffusivity were noticed in the ipsilateral internal capsule and optic nerve. It was suggested that increased fractional anisotropy, axial diffusivity and trace characterize white matter reorganization in chronic neonatal hypoxic–ischemic insults, whereas reduction in fractional anisotropy appears to characterize two types of white matter lesions, with significantly higher axial and radial diffusivities and trace being primary and slightly lower axial diffusivity being secondary. Combined with fractional anisotropy directionality map, in vivo DTI provides important indices to differentiate the chronic effects of severe neonatal hypoxic–ischemic injury and recovery globally, quantitatively and non-invasively.
    International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 10/2009; 27(6-27):607-615. DOI:10.1016/j.ijdevneu.2009.05.012 · 2.58 Impact Factor
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