Academic journal article Alcohol Research

Focus On: Magnetic Resonance-Based Studies of Fetal Alcohol Spectrum Disorders in Animal Models

Academic journal article Alcohol Research

Focus On: Magnetic Resonance-Based Studies of Fetal Alcohol Spectrum Disorders in Animal Models

Article excerpt

Animal studies using magnetic resonance (MR)-based imaging technologies, including MR imaging (MRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS) provide important insight into alcohol's early effects on the fetal brain. This article reviews how these valuable tools have been applied to the study of fetal alcohol spectrum disorders (FASD) in animal models. Compared with clinical studies of the effects of alcohol on development, using animal models allows greater control over dose, duration, and pattern of alcohol exposure. For example, research examining the effects of alcohol at different developmental stages and at various doses has helped highlight the vulnerability of the prenatal brain to very early alcohol-mediated damage. This research has important implications for clinical practice and ongoing research.

MRI

MRI is a noninvasive imaging technique that relies on powerful magnetic fields, radiofrequency pulses, and computer analysis to produce detailed pictures of organs, soft tissues, bone, and virtually all other internal body structures. This is in contrast to other imaging techniques that use ionizing radiation (e.g., X-rays). The application of MRI to the study of small animals has been facilitated by the development and availability of high--field strength MR systems (7 to 14 Tesla); custom radiofrequency coils (i.e., coils made specifically for imaging small animals); and the use of active-staining contrast agents, which are used to enhance the contrast of structures being viewed (reviewed by Petiet et al. 2007; Turnbull and Mori 2007). Advances in technology have allowed researchers to generate MR images with high spatial resolution, which is the ability to distinguish between two points, and sufficient contrast to allow delineation of the brain structures beneath the cerebral cortex, even in fetal mice (Petiet et al. 2008). The generation of MR scans that are isotropic (i.e., the volume elements [voxels] are uniform in all directions) allows these high-resolution images to be readily realigned and visualized in all planes simultaneously, thus facilitating accurate segmentation, three-dimensional reconstruction, and volumetric assessments of selected brain regions (see figure 1). It currently takes 2 to 3 hours to acquire high-resolution isotropic images of a mouse fetus, though technological advances promise to greatly reduce the amount of time (and expense) required.

STUDIES OF ALCOHOL-INDUCED DAMAGE

In addition to providing a broad perspective on normal development, MRI also has tremendous potential to aid in explaining abnormal tissue formation. To date, in the few published reports describing MRI-based analyses of alcohol-induced defects in animal models, the brain has been the region most studied (Astley et al. 1995; Godin et al. 2010; Miller et al. 1999; Parnell et al. 2009). Future application of this technology to the study of alcohol's effects on abnormal development in other organ systems (e.g., the heart and kidney) is also promising (e.g., Petiet et al. 2008).

Applying high-resolution MRI (also known as MR microscopy) to an established mouse FASD model, the authors have initiated a series of investigations aimed at identifying dose- and developmental stage--dependent patterns of alcohol-induced abnormalities. With the goal of identifying both mild and severe structural brain defects, and recognizing that defects at the severe end of the spectrum may not be compatible with postnatal viability in mice, the researchers selected a late prenatal stage (i.e., gestational day [GD] 17) for initial end point analyses. To date, results have been published from MRI-based analysis of defects following acute high-dose alcohol exposure (i.e., peak blood alcohol concentrations ranging from 350 to 440 mg/dl or 0.35 to 0.40 percent) on GD 7 and GD 8 (corresponding, respectively, to late in week 3 and early in week 4 of human prenatal development) (Godin et al. …

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