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Utilization of Magnetic Resonance Imaging in Research Involving Animal Models of Fetal Alcohol Spectrum Disorders.

Wang X, Kroenke CD - Alcohol Res (2015)

Bottom Line: Using MRI-based modalities, the FASD animal models have demonstrated decreased brain volume and abnormal brain shape, disrupted cellular morphology differentiation, altered neurochemistry, and blood perfusion.These animal studies have facilitated characterization of the direct effects of ethanol; in many cases identifying specific sequelae related to the timing and dose of exposure.Further, as a result of the ability to perform traditional (such as histological) analyses on animal brains following neuroimaging experiments, this work leads to improvements in the accuracy of our interpretations of neuroimaging findings in human studies.

View Article: PubMed Central - PubMed

Affiliation: Division of Neuroscience, Oregon National Primate Center, Oregon Health and Science University, Portland, Oregon.

ABSTRACT
It is well recognized that fetal alcohol exposure can profoundly damage the developing brain. The term fetal alcohol spectrum disorder (FASD) describes the range of deficits that result from prenatal alcohol exposure. Over the past two decades, researchers have used magnetic resonance imaging (MRI) as a noninvasive technique to characterize anatomical, physiological, and metabolic changes in the human brain that are part of FASD. As using animal models can circumvent many of the complications inherent to human studies, researchers have established and explored a number of models involving a range of species. Using MRI-based modalities, the FASD animal models have demonstrated decreased brain volume and abnormal brain shape, disrupted cellular morphology differentiation, altered neurochemistry, and blood perfusion. These animal studies have facilitated characterization of the direct effects of ethanol; in many cases identifying specific sequelae related to the timing and dose of exposure. Further, as a result of the ability to perform traditional (such as histological) analyses on animal brains following neuroimaging experiments, this work leads to improvements in the accuracy of our interpretations of neuroimaging findings in human studies.

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Effect of prenatal ethanol exposure on cerebral cortical fractional anisotropy. The two middle columns of images are laterally facing mid-cortical surface models of one rat at PD 0, PD 3, and PD 6 right hemisphere for each treatment group (ethanol) and maltose/dextrin (M/D), on which cortical fractional anisotropy (FA) at each mid-cortical surface node is projected. The outer columns represent mid-coronal FA maps for the right hemisphere of the same subjects depicted in the middle columns. Cortical FA decreased significantly with age. Additionally, cortical FA was largest, and isocortical volume smallest, in the ethanol group compared with the M/D group. This group difference is most visible in the outer layers of the cortex.NOTE: Scale bar is 4 mm. D = dorsal, V = ventral, M = medial, L = lateral, Cd = caudal, R = rostral. Figure adapted from Leigland et al. 2013b.
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f5-arcr-37-1-39: Effect of prenatal ethanol exposure on cerebral cortical fractional anisotropy. The two middle columns of images are laterally facing mid-cortical surface models of one rat at PD 0, PD 3, and PD 6 right hemisphere for each treatment group (ethanol) and maltose/dextrin (M/D), on which cortical fractional anisotropy (FA) at each mid-cortical surface node is projected. The outer columns represent mid-coronal FA maps for the right hemisphere of the same subjects depicted in the middle columns. Cortical FA decreased significantly with age. Additionally, cortical FA was largest, and isocortical volume smallest, in the ethanol group compared with the M/D group. This group difference is most visible in the outer layers of the cortex.NOTE: Scale bar is 4 mm. D = dorsal, V = ventral, M = medial, L = lateral, Cd = caudal, R = rostral. Figure adapted from Leigland et al. 2013b.

Mentions: Although a majority of neuroimaging research on early cerebral cortical development has focused on gross volume change and dysmorphology, one study used ex vivo DTI on rats to characterize prenatal ethanol exposure’s effect on cortical neuron morphological differentiation (Leigland et al. 2013b). Rats exposed to daily ethanol throughout gestation exhibited a higher diffusion fractional anisotropy (FA) in their cerebral cortex compared with age-matched M/D controls at ages PD 0, PD 3, and PD 6, indicating a higher preference for water to diffuse radially rather than parallel to the pial surface (figure 5) (see sidebar “Magnetic Resonance Imaging Techniques” for explanation of the technique). The researchers validated this finding with quantitative histological analyses of the same brains. They found that higher FA reflected a more simple and coherent cortical cellular structure, which has previously been shown with traditional invasive anatomical measurement methods (Cui et al. 2010; Davies and Smith 1981; Fabregues et al. 1985; Hammer and Scheibel 1981) to result from ethanol-induced disruption in neuronal differentiation. The framework proposed in this study in which cellular-level microstructure can be inferred by DTI-derived FA provides a novel strategy for characterizing the effects of ethanol exposure on cerebral cortical gray matter.


Utilization of Magnetic Resonance Imaging in Research Involving Animal Models of Fetal Alcohol Spectrum Disorders.

Wang X, Kroenke CD - Alcohol Res (2015)

Effect of prenatal ethanol exposure on cerebral cortical fractional anisotropy. The two middle columns of images are laterally facing mid-cortical surface models of one rat at PD 0, PD 3, and PD 6 right hemisphere for each treatment group (ethanol) and maltose/dextrin (M/D), on which cortical fractional anisotropy (FA) at each mid-cortical surface node is projected. The outer columns represent mid-coronal FA maps for the right hemisphere of the same subjects depicted in the middle columns. Cortical FA decreased significantly with age. Additionally, cortical FA was largest, and isocortical volume smallest, in the ethanol group compared with the M/D group. This group difference is most visible in the outer layers of the cortex.NOTE: Scale bar is 4 mm. D = dorsal, V = ventral, M = medial, L = lateral, Cd = caudal, R = rostral. Figure adapted from Leigland et al. 2013b.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476603&req=5

f5-arcr-37-1-39: Effect of prenatal ethanol exposure on cerebral cortical fractional anisotropy. The two middle columns of images are laterally facing mid-cortical surface models of one rat at PD 0, PD 3, and PD 6 right hemisphere for each treatment group (ethanol) and maltose/dextrin (M/D), on which cortical fractional anisotropy (FA) at each mid-cortical surface node is projected. The outer columns represent mid-coronal FA maps for the right hemisphere of the same subjects depicted in the middle columns. Cortical FA decreased significantly with age. Additionally, cortical FA was largest, and isocortical volume smallest, in the ethanol group compared with the M/D group. This group difference is most visible in the outer layers of the cortex.NOTE: Scale bar is 4 mm. D = dorsal, V = ventral, M = medial, L = lateral, Cd = caudal, R = rostral. Figure adapted from Leigland et al. 2013b.
Mentions: Although a majority of neuroimaging research on early cerebral cortical development has focused on gross volume change and dysmorphology, one study used ex vivo DTI on rats to characterize prenatal ethanol exposure’s effect on cortical neuron morphological differentiation (Leigland et al. 2013b). Rats exposed to daily ethanol throughout gestation exhibited a higher diffusion fractional anisotropy (FA) in their cerebral cortex compared with age-matched M/D controls at ages PD 0, PD 3, and PD 6, indicating a higher preference for water to diffuse radially rather than parallel to the pial surface (figure 5) (see sidebar “Magnetic Resonance Imaging Techniques” for explanation of the technique). The researchers validated this finding with quantitative histological analyses of the same brains. They found that higher FA reflected a more simple and coherent cortical cellular structure, which has previously been shown with traditional invasive anatomical measurement methods (Cui et al. 2010; Davies and Smith 1981; Fabregues et al. 1985; Hammer and Scheibel 1981) to result from ethanol-induced disruption in neuronal differentiation. The framework proposed in this study in which cellular-level microstructure can be inferred by DTI-derived FA provides a novel strategy for characterizing the effects of ethanol exposure on cerebral cortical gray matter.

Bottom Line: Using MRI-based modalities, the FASD animal models have demonstrated decreased brain volume and abnormal brain shape, disrupted cellular morphology differentiation, altered neurochemistry, and blood perfusion.These animal studies have facilitated characterization of the direct effects of ethanol; in many cases identifying specific sequelae related to the timing and dose of exposure.Further, as a result of the ability to perform traditional (such as histological) analyses on animal brains following neuroimaging experiments, this work leads to improvements in the accuracy of our interpretations of neuroimaging findings in human studies.

View Article: PubMed Central - PubMed

Affiliation: Division of Neuroscience, Oregon National Primate Center, Oregon Health and Science University, Portland, Oregon.

ABSTRACT
It is well recognized that fetal alcohol exposure can profoundly damage the developing brain. The term fetal alcohol spectrum disorder (FASD) describes the range of deficits that result from prenatal alcohol exposure. Over the past two decades, researchers have used magnetic resonance imaging (MRI) as a noninvasive technique to characterize anatomical, physiological, and metabolic changes in the human brain that are part of FASD. As using animal models can circumvent many of the complications inherent to human studies, researchers have established and explored a number of models involving a range of species. Using MRI-based modalities, the FASD animal models have demonstrated decreased brain volume and abnormal brain shape, disrupted cellular morphology differentiation, altered neurochemistry, and blood perfusion. These animal studies have facilitated characterization of the direct effects of ethanol; in many cases identifying specific sequelae related to the timing and dose of exposure. Further, as a result of the ability to perform traditional (such as histological) analyses on animal brains following neuroimaging experiments, this work leads to improvements in the accuracy of our interpretations of neuroimaging findings in human studies.

Show MeSH
Related in: MedlinePlus