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High-resolution, high-throughput magnetic resonance imaging of mouse embryonic anatomy using a fast gradient-echo sequence

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Abstract

Embryonic development in normal and genetically modified mice is commonly analysed by histological sectioning. This procedure is time-consuming, prone to artefact, and results in the loss of three-dimensional (3D) information. Magnetic resonance imaging (MRI) of embryos has the potential of non-invasively acquiring a complete 3D data set. Published methods have used spin-echo techniques with inherently high signal-to-noise ratio (SNR); however, they required either perfusion of the embryo with a contrast agent, or prolonged acquisition times to improve contrast and resolution. Here, we show that a standard preparation (i.e. paraformaldehyde fixation) of 15.5 days post-coitum embryos followed by MRI using a fast gradient-echo sequence with T1-weighting achieves high resolution and high throughput for investigating mouse embryonic anatomy. 3D data sets were acquired in overnight experiments (<9 h) with an experimental resolution of approximately 25 µm3. This spatial resolution is twofold higher than the values reported previously for comparable paraformaldehyde-fixed embryos, and it was obtained in less than a quarter of the time with sufficient SNR. Our approach combines speed, high resolution and contrast with a simple preparation technique and minimal operator time (<1 h). It allows rapid routine 3D characterisation of normal and abnormal mouse embryonic anatomy.

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References

  1. Chien KR (1996) Genes and physiology: molecular physiology in genetically engineered animals. J Clin Invest 97:901–909

    Google Scholar 

  2. Gardner-Medwin D (1986) Developmental abnormalities of the nervous system. Oxford textbook of medicine. Oxford University Press, Oxford, pp 21190–21206

  3. Clark EB (2001) Etiology of congenital cardiac malformations: epidemiology and genetics. In: Driscoll DJ (ed). Moss and Adams' heart disease in infants, children and adolescents. Lippincott Williams and Wilkins, Philadelphia pp 64–79

  4. Juriloff DM, Harris MJ (2000) Mouse models for neural tube closure defects. Hum Mol Genet 9:993–1000

    Google Scholar 

  5. Smith BR, Linney E, Huff DS, Johnson GA (1996) Magnetic resonance microscopy of embryos. Comput Med Imaging Graph 20:483–490

    Google Scholar 

  6. Toga AW (1998) Brain warping. Academic , New York

  7. Toga AW, Ambach KL, Quinn B, Shankar K, Schluender S (1996) Post mortem anatomy. In: Toga AW, Mazziotta JC (eds). Brain mapping: the methods. Academic, New York, pp 169–190

  8. Toh MY, Falk RB, Main JS (1996) Interactive brain atlas with the Visible Human Project data: development methods and techniques. Radiographics 16:1201–1206

    Google Scholar 

  9. Brune RM, Bard JB, Dubreuil C, Guest E, Hill W, Kaufman M, Stark M, Davidson D, Baldock RA (1999) A three-dimensional model of the mouse at embryonic day 9. Dev Biol 216:457–468

    Google Scholar 

  10. Kaufman MH, Brune RM, Davidson DR, Baldock RA (1998) Computer-generated three-dimensional reconstructions of serially sectioned mouse embryos. J Anat 193:323–336

    Google Scholar 

  11. Smith BR (2001) Magnetic resonance microscopy in cardiac development. Microsc Res Tech 52:323–330

    Google Scholar 

  12. Smith BR (2000) Magnetic resonance imaging analysis of embryos. In: Tuan R, Lo CW (eds) Developmental biology protocols. Humana, Totawa, New Jersey pp 211–216

  13. Smith BR, Johnson GA, Groman EV, Linney E (1994) Magnetic resonance microscopy of mouse embryos. Proc Natl Acad Sci USA 91:3530–3353

    Google Scholar 

  14. Huang GY, Wessels A, Smith BR, Linask KK, Ewart JL, Lo CW (1998) Alteration in connexin 43 gap junction gene dosage impairs conotruncal heart development. Dev Biol 198:32–44

    Google Scholar 

  15. Engelhardt RT, Johnson GA (1996) T1 rho relaxation and its application to MR histology. Magn Reson Med 35:781–786

    Google Scholar 

  16. Jacobs RE, Ahrens ET, Dickinson ME, Laidlaw D (1999) Towards a microMRI atlas of mouse development. Comput Med Imaging Graph 23:15–24

    Google Scholar 

  17. Dhenain M, Ruffins SW, Jacobs RE (2001) Three-dimensional digital mouse atlas using high-resolution MRI. Dev Biol 232:458–470

    Google Scholar 

  18. Gonzalez RC, Wintz P (1983) Digital image processing. Addison-Wesley, Reading Massachusetts

  19. Kaufman MH (1994) The atlas of mouse development. Academic, London

  20. Mansfield P, Morris PK (1982) NMR imaging in biomedicine. Academic, New York

  21. Callaghan PT (2001) Principles of magnetic resonance microscopy. Oxford University Press, Oxford

  22. Manning WJ, Wei JY, Katz SE, Litwin SE, Douglas PS (1994) In vivo assessment of LV mass in mice using high-frequency cardiac ultrasound: necropsy validation. Am J Physiol 266:H1672–H1675

    Google Scholar 

  23. Chen CN, Hoult DI, Sank VJ (1983) Quadrature detection coils—a further √2 improvement in sensitivity. J Magn Reson 54:324–327

    Google Scholar 

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Acknowledgements

This work was supported by the British Heart Foundation and the Wellcome Trust. We thank Dr Graeme Waddington for helpful discussions.

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Correspondence to Jürgen E. Schneider.

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Schneider, J.E., Bamforth, S.D., Grieve, S.M. et al. High-resolution, high-throughput magnetic resonance imaging of mouse embryonic anatomy using a fast gradient-echo sequence. MAGMA 16, 43–51 (2003). https://doi.org/10.1007/s10334-003-0002-z

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  • DOI: https://doi.org/10.1007/s10334-003-0002-z

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