Quantitative in vivo imaging of embryonic development: Opportunities and challenges

Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
Differentiation (Impact Factor: 3.44). 06/2012; 84(1):149-62. DOI: 10.1016/j.diff.2012.05.003
Source: PubMed


Animal models are critically important for a mechanistic understanding of embryonic morphogenesis. For decades, visualizing these rapid and complex multidimensional events has relied on projection images and thin section reconstructions. While much insight has been gained, fixed tissue specimens offer limited information on dynamic processes that are essential for tissue assembly and organ patterning. Quantitative imaging is required to unlock the important basic science and clinically relevant secrets that remain hidden. Recent advances in live imaging technology have enabled quantitative longitudinal analysis of embryonic morphogenesis at multiple length and time scales. Four different imaging modalities are currently being used to monitor embryonic morphogenesis: optical, ultrasound, magnetic resonance imaging (MRI), and micro-computed tomography (micro-CT). Each has its advantages and limitations with respect to spatial resolution, depth of field, scanning speed, and tissue contrast. In addition, new processing tools have been developed to enhance live imaging capabilities. In this review, we analyze each type of imaging source and its use in quantitative study of embryonic morphogenesis in small animal models. We describe the physics behind their function, identify some examples in which the modality has revealed new quantitative insights, and then conclude with a discussion of new research directions with live imaging.

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Available from: Jonathan T Butcher
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    • "In vivo embryonic imaging has become widely used to understand embryonic CV morphogenesis both qualitatively and quantitatively. Various modalities are currently employed, summarized in Table 2 (Gregg and Butcher, 2012). The fluorescent stereomicroscope remains a prominent tool for experiments and observation, including assessment of CV dimensions and tracking intracardiac flow patterns (Faber et al., 1974; Keller et al., 1990, 1996; Hogers et al., 1995; Al Naieb et al., 2012; Kowalski et al., 2014). "
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    ABSTRACT: Innovative research on the interactions between biomechanical load and cardiovascular (CV) morphogenesis by multiple investigators over the past 3 decades, including the application of bioengineering approaches, has shown that the embryonic heart adapts both structure and function in order to maintain cardiac output to the rapidly growing embryo. Acute adaptive hemodynamic mechanisms in the embryo include the redistribution of blood flow within the heart, dynamic adjustments in heart rate and developed pressure, and beat to beat variations in blood flow and vascular resistance. These biomechanically relevant events occur coincident with adaptive changes in gene expression and trigger adaptive mechanisms that include alterations in myocardial cell growth and death, regional and global changes in myocardial architecture, and alterations in central vascular morphogenesis and remodeling. These adaptive mechanisms allow the embryo to survive these biomechanical stresses (environmental, maternal) and to compensate for developmental errors (genetic). Recent work from numerous laboratories shows that a subset of these adaptive mechanisms is present in every developing multicellular organism with a "heart" equivalent structure. This chapter will provide the reader with an overview of some of the approaches used to quantify embryonic CV functional maturation and performance, provide several illustrations of experimental interventions that explore the role of biomechanics in the regulation of CV morphogenesis including the role of computational modeling, and identify several critical areas for future investigation as available experimental models and methods expand.
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    • "Differences in the efficacy of sample staining can cause variability in the quality and imaging resolution achieved (Cheng et al., 2011; Hiraiwa et al., 2013). Micro-CT systems currently available are used mostly to examine postmortem fixed tissue samples, as the imaging cannot be acquired in real-time (Tobita et al., 2010; Gregg and Butcher, 2012). We have found micro-CT scanning of developing mouse fetus and newborn animals fixed and stained with iodine provides high resolution images suitable for cardiovas- cular phenotyping. "
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    ABSTRACT: Mouse model is ideal for investigating the genetic and developmental etiology of congenital heart disease. However, cardiovascular phenotyping for the precise diagnosis of structural heart defects in mice remain challenging. With rapid advances in imaging techniques, there are now high throughput phenotyping tools available for the diagnosis of structural heart defects. In this review, we discuss the efficacy of four different imaging modalities for congenital heart disease diagnosis in fetal/neonatal mice, including noninvasive fetal echocardiography, micro-computed tomography (micro-CT), micro-magnetic resonance imaging (micro-MRI), and episcopic fluorescence image capture (EFIC) histopathology. The experience we have gained in the use of these imaging modalities in a large-scale mouse mutagenesis screen have validated their efficacy for congenital heart defect diagnosis in the tiny hearts of fetal and newborn mice. These cutting edge phenotyping tools will be invaluable for furthering our understanding of the developmental etiology of congenital heart disease. Birth Defects Research (Part C) 99:93-105, 2013. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Jun 2013 · Birth Defects Research Part C Embryo Today Reviews

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