Functional Imaging of the Prenatal Brain


In utero magnetic resonance imaging (MRI) has significantly increased our knowledge on early fetal brain development. Especially the possibility to expand standard clinical applications of imaging structure to functional imaging has increased the opportunities but also introduced major challenges in the field regarding motion artifacts, group analysis, and generating structural templates. This chapter gives an overview on fetal functional imaging from stimulation to resting-state studies and discusses critical challenges in data analysis. Fetal functional MRI is a powerful approach investigating brain development in utero and has the potential of generating biomarkers for developmental prognosis in the future.


Diffusion Tensor Imaging Blood Oxygen Level Dependent Hemodynamic Response Function Fetal MRIImagingMagnetic Resonance Imaging Image Functional Magnetic Resonance Imaging 
These keywords were added by machine and not by the authors.


  1. Behzadi, Y., Restom, K., Liau, J., & Liu, T. T. (2007). A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. NeuroImage, 37(1), 90–101. doi: 10.1016/j.neuroimage.2007.04.042.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Biswal, B. B. (2012). Resting state fMRI: A personal history. NeuroImage, 62(2), 938–944. doi: 10.1016/j.neuroimage.2012.01.090.CrossRefPubMedGoogle Scholar
  3. Brewerton, L. J., Chari, R. S., Liang, Y., & Bhargava, R. (2005). Fetal lung-to-liver signal intensity ratio at MR imaging: Development of a normal scale and possible role in predicting pulmonary hypoplasia in utero. Radiology, 235(3), 1005–1010.CrossRefPubMedGoogle Scholar
  4. Brugger, P. C., Stuhr, F., Lindner, C., & Prayer, D. (2006). Methods of fetal MR: Beyond T2-weighted imaging. European Journal of Radiology, 57(2), 172–181.CrossRefPubMedGoogle Scholar
  5. Chen, Q., & Levine, D. (2001). Fast fetal magnetic resonance imaging techniques. Topics in Magnetic Resonance Imaging, 12(1), 67–79.CrossRefPubMedGoogle Scholar
  6. De Vries, J. I. P., Visser, G. H. A., & Prechtl, H. F. R. (1982). The emergence of fetal behaviour. I. Qualitative aspects. Early Human Development, 7(4), 301–322. doi: 10.1016/0378-3782(82)90033-0.CrossRefPubMedGoogle Scholar
  7. Derntl, B., Krajnik, J., Kollndorfer, K., Bijak, M., Nemec, U., Leithner, K., …, Schöpf, V. (2015). Stress matters! Psychophysiological and emotional loadings of pregnant women undergoing fetal magnetic resonance imaging. BMC Pregnancy and Childbirth, 15, 25.Google Scholar
  8. Dittrich, E., Kasprian, G., Prayer, D., & Langs, G. (2011). Atlas learning in fetal brain development. Topics in Magnetic Resonance Imaging, 22(3), 107–111.CrossRefPubMedGoogle Scholar
  9. Dittrich, E., Riklin Raviv, T., Kasprian, G., Donner, R., Brugger, P. C., Prayer, D., et al. (2014). A spatio-temporal latent atlas for semi-supervised learning of fetal brain segmentations and morphological age estimation. Medical Image Analysis, 18(1), 9–21. doi: 10.1016/ Scholar
  10. Evans, A. C., Collins, D. L., Mills, S. R., Brown, E. D., Kelly, R. L., & Peters, T. M. (1993). 3D statistical neuroanatomical models from 305 MRI volumes. In 1993 IEEE Conference Record Nuclear Science Symposium and Medical Imaging Conference (pp. 1813–1817). IEEE. doi:10.1109/NSSMIC.1993.373602.Google Scholar
  11. Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., …, Dale, A. M. (2002). Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain. Neuron, 33(3), 341–355.Google Scholar
  12. Friston, K. J., Williams, S., Howard, R., Frackowiak, R. S., & Turner, R. (1996). Movement-related effects in fMRI time-series. Magnetic Resonance in Medicine, 35(3), 346–355.CrossRefPubMedGoogle Scholar
  13. Fulford, J., Vadeyar, S. H., Dodampahala, S. H., Moore, R. J., Young, P., Baker, P. N., …, Gowland, P. A. (2003). Fetal brain activity in response to a visual stimulus. Human Brain Mapping, 20(4), 239–245.Google Scholar
  14. Fulford, J., Vadeyar, S. H., Dodampahala, S. H., Ong, S., Moore, R. J., Baker, P. N., …, Gowland, P. (2004). Fetal brain activity and hemodynamic response to a vibroacoustic stimulus. Human Brain Mapping, 22(2), 116–121.Google Scholar
  15. Glover, P., Hykin, J., Gowland, P., Wright, J., Johnson, I., & Mansfield, P. (1995). An assessment of the intrauterine sound intensity level during obstetric echo-planar magnetic resonance imaging. British Journal of Radiology, 68(814), 1090–1094.CrossRefPubMedGoogle Scholar
  16. Gorgolewski, K., Burns, C. D., Madison, C., Clark, D., Halchenko, Y. O., Waskom, M. L., et al. (2011). Nipype: A flexible, lightweight and extensible neuroimaging data processing framework in python. Frontiers in Neuroinformatics, 5, 13. doi: 10.3389/fninf.2011.00013.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Habas, P. A., Kim, K., Corbett-Detig, J. M., Rousseau, F., Glenn, O. A., Barkovich, A. J., et al. (2010). A spatiotemporal atlas of MR intensity, tissue probability and shape of the fetal brain with application to segmentation. NeuroImage, 53(2), 460–470. doi: 10.1016/j.neuroimage.2010.06.054.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Hykin, J., Moore, R., Duncan, K., Clare, S., Baker, P., Johnson, I., …, Gowland, P. (1999). Fetal brain activity demonstrated by functional magnetic resonance imaging. Lancet, 354(9179), 645–646.Google Scholar
  19. Jardri, R., Houfflin-Debarge, V., Delion, P., Pruvo, J.-P., Thomas, P., & Pins, D. (2012). Assessing fetal response to maternal speech using a noninvasive functional brain imaging technique. International Journal of Developmental Neuroscience, 30(2), 159–161. doi: 10.1016/j.ijdevneu.2011.11.002.CrossRefPubMedGoogle Scholar
  20. Jardri, R., Pins, D., Houfflin-Debarge, V., Chaffiotte, C., Rocourt, N., Pruvo, J.-P., …, Thomas, P. (2008). Fetal cortical activation to sound at 33 weeks of gestation: A functional MRI study. Neuroimage, 42(1), 10–18.Google Scholar
  21. Jenkinson, M., Bannister, P., Brady, M., & Smith, S. (2002). Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage, 17(2), 825–841.CrossRefPubMedGoogle Scholar
  22. Jenkinson, M., Beckmann, C. F., Behrens, T. E. J., Woolrich, M. W., & Smith, S. M. (2012). FSL. NeuroImage, 62(2), 782–790. doi: 10.1016/j.neuroimage.2011.09.015.CrossRefPubMedGoogle Scholar
  23. Kanal, E., Gillen, J., Evans, J. A., Savitz, D. A., & Shellock, F. G. (1993). Survey of reproductive health among female MR workers. Radiology, 187(2), 395–399.CrossRefPubMedGoogle Scholar
  24. Kim, K., Habas, P. A., Rousseau, F., Glenn, O. A., Barkovich, A. J., & Studholme, C. (2010). Intersection based motion correction of multislice MRI for 3-D in utero fetal brain image formation. IEEE Transactions on Medical Imaging, 29(1), 146–158. doi: 10.1109/TMI.2009.2030679.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Kok, R. D., de Vries, M. M., Heerschap, A., & van den Berg, P. P. (2004). Absence of harmful effects of magnetic resonance exposure at 1.5 T in utero during the third trimester of pregnancy: A follow-up study. Magnetic Resonance Imaging, 22(6), 851–854.CrossRefPubMedGoogle Scholar
  26. Krüger, G., & Glover, G. H. (2001). Physiological noise in oxygenation-sensitive magnetic resonance imaging. Magnetic Resonance in Medicine, 46(4), 631–637.CrossRefPubMedGoogle Scholar
  27. Kuklisova-Murgasova, M., Aljabar, P., Srinivasan, L., Counsell, S. J., Doria, V., Serag, A., …, Rueckert, D. (2011). A dynamic 4D probabilistic atlas of the developing brain. NeuroImage, 54(4), 2750–2763. doi:10.1016/j.neuroimage.2010.10.019.Google Scholar
  28. Lan, L. M., Yamashita, Y., Tang, Y., Sugahara, T., Takahashi, M., Ohba, T., et al. (2000). Normal fetal brain development: MR imaging with a half-Fourier rapid acquisition with relaxation enhancement sequence. Radiology, 215(1), 205–210.CrossRefPubMedGoogle Scholar
  29. Lowe, M. J. (2012). The emergence of doing “nothing” as a viable paradigm design. NeuroImage, 62(2), 1146–1151. doi: 10.1016/j.neuroimage.2012.01.014.CrossRefPubMedGoogle Scholar
  30. Mailath-Pokorny, M., Kasprian, G., Mitter, C., Schöpf, V., Nemec, U., & Prayer, D. (2012). Magnetic resonance methods in fetal neurology. Seminars in Fetal & Neonatal Medicine, 17(5), 278–284. doi: 10.1016/j.siny.2012.06.002.CrossRefGoogle Scholar
  31. Moore, R. J., Vadeyar, S., Fulford, J., Tyler, D. J., Gribben, C., Baker, P. N., …, Gowland, P. A. (2001). Antenatal determination of fetal brain activity in response to an acoustic stimulus using functional magnetic resonance imaging. Human Brain Mapping, 12(2), 94–99.Google Scholar
  32. Ogawa, S., Lee, T. M., Kay, A. R., & Tank, D. W. (1990). Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proceedings of the National Academy of Sciences of the United States of America, 87(24), 9868–9872.CrossRefPubMedPubMedCentralGoogle Scholar
  33. Ogawa, S., Tank, D. W., & Menon, R. (1992). Intrinsic signal changes accompanying sensory stimulation: Functional brain mapping resonance imaging. Proceedings of the National Academy of Sciences, 89, 5951–5955.CrossRefGoogle Scholar
  34. Raichle, M. E., & Snyder, A. Z. (2007). A default mode of brain function: A brief history of an evolving idea. NeuroImage, 37(4), 1083–1090. doi: 10.1016/j.neuroimage.2007.02.041. discussion 1097–9.CrossRefPubMedGoogle Scholar
  35. Riklin-Raviv, T., Van Leemput, K., Menze, B. H., Wells, W. M., & Golland, P. (2010). Segmentation of image ensembles via latent atlases. Medical Image Analysis, 14(5), 654–665. doi: 10.1016/ Scholar
  36. Roche, A. (2011). A four-dimensional registration algorithm with application to joint correction of motion and slice timing in fMRI. IEEE Transactions on Medical Imaging, 30(8), 1546–1554. doi: 10.1109/TMI.2011.2131152.CrossRefPubMedGoogle Scholar
  37. Rosazza, C., Minati, L., Ghielmetti, F., Mandelli, M. L., & Bruzzone, M. G. (2012). Functional connectivity during resting-state functional MR imaging: Study of the correspondence between independent component analysis and region-of-interest-based methods. AJNR. American Journal of Neuroradiology, 33(1), 180–187. doi: 10.3174/ajnr.A2733.CrossRefPubMedGoogle Scholar
  38. Rousseau, F., Oubel, E., Pontabry, J., Schweitzer, M., Studholme, C., Koob, M., et al. (2013). BTK: An open-source toolkit for fetal brain MR image processing. Computer Methods and Programs in Biomedicine, 109(1), 65–73. doi: 10.1016/j.cmpb.2012.08.007.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Salimi-Khorshidi, G., Douaud, G., Beckmann, C. F., Glasser, M. F., Griffanti, L., & Smith, S. M. (2014). Automatic denoising of functional MRI data: Combining independent component analysis and hierarchical fusion of classifiers. NeuroImage, 90, 449–468. doi: 10.1016/j.neuroimage.2013.11.046.CrossRefPubMedPubMedCentralGoogle Scholar
  40. Schöpf, V., Dittrich, E., Berger-Kulemann, V., Kasprian, G., Kollndorfer, K., & Prayer, D. (2013). Advanced MRI techniques of the fetal brain. Der Radiologe, 53(2), 136–140. doi: 10.1007/s00117-012-2401-5.CrossRefPubMedGoogle Scholar
  41. Schöpf, V., Kasprian, G., Brugger, P., & Prayer, D. (2012). Watching the fetal brain at “rest”. International Journal of Developmental Neuroscience, 30(1), 11–17.CrossRefPubMedGoogle Scholar
  42. Schöpf, V., Kasprian, G., Schwindt, J., Kollndorfer, K., & Prayer, D. (2012). Visualization of resting-state networks in utero. Ultrasound in Obstetrics and Gynecology, 39, 487–488.CrossRefPubMedGoogle Scholar
  43. Schwartz, J. L., & Crooks, L. E. (1982). NMR imaging produces no observable mutations or cytotoxicity in mammalian cells. AJR. American Journal of Roentgenology, 139(3), 583–585.CrossRefPubMedGoogle Scholar
  44. Serag, A., Aljabar, P., Ball, G., Counsell, S., Boardman, J., Hajnal, J., & Rueckert, D. (2010). Developmental signal intensity changes in subcortical structures of the perinatal brain detected using multi-modal MRI. In MICCAI 2010 Workshop STIA’10 (pp. 1–8).Google Scholar
  45. Seshamani, S., Fogtmann, M., Cheng, X., Thomason, M., Gatenby, C., & Studholme, C. (2013). Cascaded slice to volume registration for moving fetal FMRI. In 2013 IEEE 10th International Symposium on Biomedical Imaging (pp. 796–799). IEEE. doi:10.1109/ISBI.2013.6556595.Google Scholar
  46. Shellock, F. G., & Crues, J. V. (2004). MR procedures: Biologic effects, safety, and patient care. Radiology, 232(3), 635–652. doi: 10.1148/radiol.2323030830.CrossRefPubMedGoogle Scholar
  47. Shellock, F. G., & Kanal, E. (1991). Policies, guidelines, and recommendations for MR imaging safety and patient management. SMRI Safety Committee. Journal of Magnetic Resonance Imaging, 1(1), 97–101.CrossRefPubMedGoogle Scholar
  48. Smith, F. W., Adam, A. H., & Phillips, W. D. (1983). NMR imaging in pregnancy. Lancet, 1(8314-5), 61–62.CrossRefPubMedGoogle Scholar
  49. Snyder, A. Z., & Raichle, M. E. (2012). A brief history of the resting state: The Washington University perspective. NeuroImage, 62(2), 902–910. doi: 10.1016/j.neuroimage.2012.01.044.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Supino, R., Bottone, M. G., Pellicciari, C., Caserini, C., Bottiroli, G., Belleri, M., et al. (2001). Sinusoidal 50 Hz magnetic fields do not affect structural morphology and proliferation of human cells in vitro. Histology and Histopathology, 16, 719–726.PubMedGoogle Scholar
  51. Talairach, J., & Tournoux, P. (1988). Co-planar stereotaxic Atlas of the human brain: 3-D proportional system: An approach to cerebral imaging. Stuttgart: Thieme Publishers.Google Scholar
  52. Thomason, M. E., Dassanayake, M. T., Shen, S., Katkuri, Y., Alexis, M., Anderson, A. L., …, Romero, R. (2013). Cross-hemispheric functional connectivity in the human fetal brain. Science Translational Medicine, 5(173), 173ra24–173ra24. doi:10.1126/scitranslmed.3004978.Google Scholar
  53. Yamashita, Y., Namimoto, T., Abe, Y., Takahashi, M., Iwamasa, J., Miyazaki, K., et al. (1997). MR imaging of the fetus by a HASTE sequence. AJR. American Journal of Roentgenology, 168(2), 513–519.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Institute of PsychologyUniversity of GrazGrazAustria
  2. 2.Computational Imaging Research Lab (CIR), Department of Biomedical Imaging and Image-Guided TherapyMedical University of ViennaViennaAustria

Personalised recommendations