Limits...
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.

Show MeSH

Related in: MedlinePlus

Reconstructed brains of a control fetal mouse at gestational age 17 (A) along with the brains of ethanol-exposed fetuses having mid-facial abnormality (B and C). Segmented magnetic resonance microscopy scans of control (A) and ethanol-exposed (B and C) fetuses were reconstructed to yield whole brain (frontal view). Although the affected fetus in (B) had a normal-appearing face (figure not shown here), a slight widening of the space between the cerebral hemispheres (as evidenced by visibility of the septal region and diencephalon) can be seen as compared with control (A). Missing olfactory bulb and rostral union of the cerebral hemispheres can be seen in fetus (C).NOTE: Figure adapted from (Godin et al. 2010).
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4476603&req=5

f3-arcr-37-1-39: Reconstructed brains of a control fetal mouse at gestational age 17 (A) along with the brains of ethanol-exposed fetuses having mid-facial abnormality (B and C). Segmented magnetic resonance microscopy scans of control (A) and ethanol-exposed (B and C) fetuses were reconstructed to yield whole brain (frontal view). Although the affected fetus in (B) had a normal-appearing face (figure not shown here), a slight widening of the space between the cerebral hemispheres (as evidenced by visibility of the septal region and diencephalon) can be seen as compared with control (A). Missing olfactory bulb and rostral union of the cerebral hemispheres can be seen in fetus (C).NOTE: Figure adapted from (Godin et al. 2010).

Mentions: In a series of mouse FASD studies, researchers used ex vivo MRI to examine the effect of acute ethanol insult on GD 7, 8, 9, and 10, a time range that corresponds to human GWs 3 to 4 (Godin et al. 2010; O’Leary-Moore et al. 2010; Parnell et al. 2009, 2013). To characterize ethanol-induced structural brain abnormalities, they analyzed high-resolution MR images of each fetus dissected on GD 17 (see figure 2). They measured key growth metrics such as brain width, mid-sagittal brain length, and third ventricle width in a single image plane (see figure 2A). They also segmented and then reconstructed regional brain structures (e.g. cerebral cortex, ventricles, cerebellum, etc.) to quantify their volume and morphology in three dimension (see figure 2B and C). In the fetuses exposed to ethanol in utero, the researchers found notable volume reductions across various brain regions, which were accompanied by increased ventricular sizes. They also observed regional brain morphology changes including holoprosencephaly, or the absence of midline cerebral structures, and widened space between cerebral hemispheres (see figure 3B and C). These results demonstrate that an acute maternal alcohol insult on GD 7 to 10 leads to a spectrum of forebrain deficiencies in mouse fetuses. Importantly, some animals that exhibited CNS malformations did not have facial dysmorphology. This series of studies employing an acute, high-dose maternal ethanol treatment paradigm helped titrate sensitive periods for a variety of malformations and extended our knowledge of the dependency of ethanol teratogenesis on the timing of exposure during gestation.


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

Wang X, Kroenke CD - Alcohol Res (2015)

Reconstructed brains of a control fetal mouse at gestational age 17 (A) along with the brains of ethanol-exposed fetuses having mid-facial abnormality (B and C). Segmented magnetic resonance microscopy scans of control (A) and ethanol-exposed (B and C) fetuses were reconstructed to yield whole brain (frontal view). Although the affected fetus in (B) had a normal-appearing face (figure not shown here), a slight widening of the space between the cerebral hemispheres (as evidenced by visibility of the septal region and diencephalon) can be seen as compared with control (A). Missing olfactory bulb and rostral union of the cerebral hemispheres can be seen in fetus (C).NOTE: Figure adapted from (Godin et al. 2010).
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f3-arcr-37-1-39: Reconstructed brains of a control fetal mouse at gestational age 17 (A) along with the brains of ethanol-exposed fetuses having mid-facial abnormality (B and C). Segmented magnetic resonance microscopy scans of control (A) and ethanol-exposed (B and C) fetuses were reconstructed to yield whole brain (frontal view). Although the affected fetus in (B) had a normal-appearing face (figure not shown here), a slight widening of the space between the cerebral hemispheres (as evidenced by visibility of the septal region and diencephalon) can be seen as compared with control (A). Missing olfactory bulb and rostral union of the cerebral hemispheres can be seen in fetus (C).NOTE: Figure adapted from (Godin et al. 2010).
Mentions: In a series of mouse FASD studies, researchers used ex vivo MRI to examine the effect of acute ethanol insult on GD 7, 8, 9, and 10, a time range that corresponds to human GWs 3 to 4 (Godin et al. 2010; O’Leary-Moore et al. 2010; Parnell et al. 2009, 2013). To characterize ethanol-induced structural brain abnormalities, they analyzed high-resolution MR images of each fetus dissected on GD 17 (see figure 2). They measured key growth metrics such as brain width, mid-sagittal brain length, and third ventricle width in a single image plane (see figure 2A). They also segmented and then reconstructed regional brain structures (e.g. cerebral cortex, ventricles, cerebellum, etc.) to quantify their volume and morphology in three dimension (see figure 2B and C). In the fetuses exposed to ethanol in utero, the researchers found notable volume reductions across various brain regions, which were accompanied by increased ventricular sizes. They also observed regional brain morphology changes including holoprosencephaly, or the absence of midline cerebral structures, and widened space between cerebral hemispheres (see figure 3B and C). These results demonstrate that an acute maternal alcohol insult on GD 7 to 10 leads to a spectrum of forebrain deficiencies in mouse fetuses. Importantly, some animals that exhibited CNS malformations did not have facial dysmorphology. This series of studies employing an acute, high-dose maternal ethanol treatment paradigm helped titrate sensitive periods for a variety of malformations and extended our knowledge of the dependency of ethanol teratogenesis on the timing of exposure during gestation.

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