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Item Computed tomography assessment of peripubertal craniofacial morphology in a sheep model of binge alcohol drinking in the first trimester(Elsevier, 2015-11) Birch, Sharla M.; Lenox, Mark W.; Kornegay, Joe N.; Shen, Li; Ai, Huisi; Ren, Xiaowei; Goodlett, Charles R.; Cudd, Tim A.; Washburn, Shannon E.; Department of Medical & Molecular Genetics, IU School of MedicineIdentification of facial dysmorphology is essential for the diagnosis of fetal alcohol syndrome (FAS); however, most children with fetal alcohol spectrum disorders (FASD) do not meet the dysmorphology criterion. Additional objective indicators are needed to help identify the broader spectrum of children affected by prenatal alcohol exposure. Computed tomography (CT) was used in a sheep model of prenatal binge alcohol exposure to test the hypothesis that quantitative measures of craniofacial bone volumes and linear distances could identify alcohol-exposed lambs. Pregnant sheep were randomly assigned to four groups: heavy binge alcohol, 2.5 g/kg/day (HBA); binge alcohol, 1.75 g/kg/day (BA); saline control (SC); and normal control (NC). Intravenous alcohol (BA; HBA) or saline (SC) infusions were given three consecutive days per week from gestation day 4-41, and a CT scan was performed on postnatal day 182. The volumes of eight skull bones, cranial circumference, and 19 linear measures of the face and skull were compared among treatment groups. Lambs from both alcohol groups showed significant reduction in seven of the eight skull bones and total skull bone volume, as well as cranial circumference. Alcohol exposure also decreased four of the 19 craniofacial measures. Discriminant analysis showed that alcohol-exposed and control lambs could be classified with high accuracy based on total skull bone volume, frontal, parietal, or mandibular bone volumes, cranial circumference, or interorbital distance. Total skull volume was significantly more sensitive than cranial circumference in identifying the alcohol-exposed lambs when alcohol-exposed lambs were classified using the typical FAS diagnostic cutoff of ≤10th percentile. This first demonstration of the usefulness of CT-derived craniofacial measures in a sheep model of FASD following binge-like alcohol exposure during the first trimester suggests that volumetric measurement of cranial bones may be a novel biomarker for binge alcohol exposure during the first trimester to help identify non-dysmorphic children with FASD.Item HEAD CIRCUMFERENCE AS PREDICTED BY FACIAL MEASURES IN MOUSE MODEL OF FASD(Office of the Vice Chancellor for Research, 2012-04-13) Timm, Floyd A.; Ward, Richard E.; Wetherill, Leah; Ai, Huisi; Shen, Li; Anthony, Bruce; Zhou, Feng C.Intrauterine exposure to ethanol produces a myriad of anomalies, many tied to the developing brain. Both dose and duration of exposure are suggested to have cumulative effects on brain growth; however, brain volume is difficult to obtain directly, so a commonly used indirect measure of brain volume has been the occipital frontal circumference (OFC) in humans (Malina and Bouchard). In this study, we investigated the relationship of craniofacial measurements and exposure histories against skull circumference in C57BL/6J (Jackson Laboratory) mice. Three alcohol treatment groups were used, which differed in dose of alcohol administered and/or the duration of treatment during gestation. All pups were surrogated at birth with normal dams and received microCT at postnatal day (P) 21. Individual measurement comparisons were made between treatment groups, a control sample of chow fed, and matching groups of pair-fed (isocalorically linked liquid diet). Linear craniofacial measurements were derived from micro-CT images, and a measure of head circumference was constructed using the MxView software (Philips). A multiple linear regression was used to evaluate the facial measurements that best predicted circumference. Variables explored were facial measurements as well as treatment and gender. The model, using a constant, mid facial depth, inner orbital width, and bigonial width predicted 68.8% of variance in circumference (N=164, R2=.688, p=.006). In conclusion, a small set of facial measurements can moderately predict circumference in mice. However, in a small exploratory study, there is an indication that alcohol exposure is a significant factor in the degree to which circumference relates to total brain volume. 2Department of Anthropology Indiana University Purdue University Indianapolis, Indianapolis, Indiana, 46202 3Medical and Molecular Genetics, Indiana University School of Medicine Indianapolis, Indiana, 46202 4Department of Radiology and Imaging Sciences Indiana University School of Medicine, Indianapolis, IN 46202 5Stark Neuroscience Research Institute, Indiana University School of Medicine Indianapolis, Indiana, 46202