PMC

MRM scans and reconstructions illustrate additional dysmorphic features of the fetus pictured in . Coronal scans made at the level of the eyes illustrate clefting of the secondary palate (black arrow in b), no apparent tongue, and this fetus’s very narrow mandible (white arrow in b). A posterior view of the reconstructed mesencephalic and fourth ventricle show stenosis (narrowing) at the level of the aqueductal isthmus (arrow in d). Shown in (a & c) are comparable views of a control fetus.

Additional light micrographs along with coronal MRM scans and reconstructions and histological sections of the fetus pictured in illustrate its dysmorphic features as compared to control (a, c, e, g, i) Included are anophthalmia and snout foreshortening (evident in b), short nasal septum and small nasal cavity (arrow in d) [scan made at the level of the line in (b)], third ventricular enlargement (arrow in f), pituitary agenesis (h; compare to control, arrow in g), and apparent absence of the corpus callosum (j; compare to control, arrow in i). Bar in i = 0.5 mm

MRM and routine histology illustrate olfactory nerve abnormality in a holoprosencephalic fetus. As compared to an MRM image of a normal coronal scan (a; arrow indicates olfactory bulb) that from an ethanol-exposed fetus (b; fetus also shown in ), reveals absence of the olfactory bulbs and the presence of an aberrant intracranial median mass that is located dorsal to the nasal septum (boxed area). Subsequent examination of histological sections through this region revealed that the tissue is continuous, through the cribriform plate, with the nasal epithelium (arrow in d). Bar in c = 0.5 mm, in d = 0.2 mm

Horizontal MRM scans at 2 different levels through a control (a. d) and 2 affected fetuses (b, e with semilobar HPE & c, f with alobar HPE; shown in , respectively) illustrate rostro-median tissue loss. The septal region (long arrow), which is apparent in the rostral midline of the control, is absent in the affected fetuses. In the more mildly affected fetus (b, e), the striatal tissue (short arrow) can be defined and, in the absence of the septal region, is united across the midline. In the more severely affected fetus (c, f), MRM does not allow clear identification of the striatal boundaries. Notable in both affected fetuses is the vastly enlarged and rostro-medially fused lateral ventricles (✯).

Ethanol-induces volume changes in selected regions of GD 17 fetal mouse brains following acute GD 7 exposure. Data is expressed to illustrate the broad range of insult. Mean values from 7 control fetuses are indicated by a black dot, with a bar indicating the 95% confidence interval of the control mean. Values for the 5 ethanol-exposed animals with overt HPE are expressed as x’s; and for all of the other ethanol-exposed animals (n=14) a grey circle is employed. Please note differing scales on the right and left, as needed to facilitate representation of the data.

Shown are the face and reconstructed brain of a control GD 17 fetal mouse along with the faces and brains of ethanol-exposed fetuses having semilobar and alobar holoprosencephaly (HPE). As compared to the control face (a), those fetuses with HPE (b–f) have varying degrees of midfacial abnormality; each presenting with a long (from nose to mouth) upper lip, a small nose with closely-set nostrils, and micrognathia (narrow, pointed chin), the latter of which is severe in the specimens shown in (b) and (f). Segmented MRM scans of control (g, m, s) and ethanol-exposed fetuses (h–l, n–r, t–x) were reconstructed to yield whole brain (frontal view, g–l; dorsal view, m–r) and ventricular system (s–x) images. Notable forebrain abnormalities include varying degrees of olfactory bulb deficiency and rostral union of the cerebral hemispheres, accompanied by dysmorphic lateral ventricles. From a dorsal view, the mid- and hindbrain and their ventricles appear relatively normal in all of the affected fetuses. Color codes for the segmented brain regions are shown at the bottom of the Figure.

MRM scans of GD 17 mouse fetuses allow for linear measurements, regional segmentation, and 3D reconstruction. Illustrated in (a) is a horizontal scan with lines depicting sites of linear measurement as follows: brain width (biparietal distance), line 1; bulbothalamic distance, line 2; mid-sagittal brain length, line 3; frontothalamic distance, line 4; third ventricle width, line 5. [Cerebellar width (transverse cerebellar distance, not included) was measured at its greatest dimension.] Manual segmentation, as depicted by the color-coded regions in (b) allowed for subsequent 3D reconstruction (c) and analyses of selected brain regions. In (c), the upper right quadrant of the brain has been removed to allow for visualization of the interior structures. Color-codes for the segmented brain regions shown are at the bottom of the Figure. Other regions that were also examined for each of the animals in this study, but are not shown in this illustration, are the pituitary and the ocular globe and lens of each eye. (modified from Figs. 1 & 2, )

Shown are the face, brain reconstruction, and histological sections of a control and 4 dysmorphic GD 17 fetal mice. A common feature among the ethanol-exposed animals is cortical dysplasia/heterotopia in the absence of overt HPE. As compared to the control (a), the affected fetuses have faces that appear relatively normal (b), or that present with a long upper lip along with severe micrognathia (c), or foreshortening (d; also note ) or median cleft of the snout (e). As viewed from the front, reconstructed MRM scans illustrate a slight widening of the space between the cerebral hemispheres (as evidenced by visibility of the septal region and diencephalon) in the affected fetuses (g–j) as compared to control (f). (Color codes for the segmented brain regions are shown beneath the 3D reconstructions.) Also evident in (g) and (j) are irregularities on the cerebral cortical surface (arrows). Subsequent histological analyses of these and the other 2 fetuses shown in this Figure identified these structures as cortical dysplasia/heterotopias (arrows in l–o, 4X; q–t, 10X). Bar in k = 0.5mm, in p = 0.2 mm