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

The imaging techniques magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) provide valuable tools for studying brain structure and neurochemistry in fetal alcohol spectrum disorders (FASD). Although the application of magnetic resonance-based methodologies to the study of FASD in animal models is in its infancy, it already has provided new clinically relevant insights and holds significant promise to further extend our understanding of alcohol's effects on the developing fetus. KEY WORDS: Prenatal alcohol exposure; fetal alcohol spectrum disorders; fetus; brain; birth defects; magnetic resonance imaging; magnetic resonance spectroscopy; diffusion tensor imaging; animal models; animal studies

Animal studies using magnetic resonance (MR)based imaging technologies, including MR imaging (MRI), diffusion tensor imaging (DTI), andMR 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 alcoholmediated 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., Xrays). 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 activestaining 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 ofMR scans that are isotropic (i.e., the volume elements [voxels] are uniform in all directions) allows these highresolution images to be readily realigned and visualized in all planes simultaneously, thus facilitating accurate segmentation, threedimensional reconstruction, and volumetric assessments of selected brain regions (see figure 1). It currently takes 2 to 3 hours to acquire highresolution isotropic images of a mouse fetus, though technological advances promise to greatly reduce the amount of time (and expense) required.

Studies of AlcoholInduced 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 MRIbased analyses of alcoholinduced 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 highresolution MRI (also known as MR microscopy) to an established mouse FASD model, the authors have initiated a series of investigations aimed at identifying doseand developmental stage-dependent patterns of alcoholinduced abnormalities. …

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