, Volume 56, Issue 7, pp 561–567 | Cite as

Regional apparent diffusion coefficient values in 3rd trimester fetal brain

  • Chen Hoffmann
  • Boaz Weisz
  • Shlomo Lipitz
  • Gal Yaniv
  • Eldad Katorza
  • Dafi Bergman
  • Anat Biegon
Paediatric Neuroradiology



Apparent diffusion coefficient (ADC) values in the developing fetus can be used in the diagnosis and prognosis of prenatal brain pathologies. To this end, we measured regional ADC in a relatively large cohort of normal fetal brains in utero.


Diffusion-weighted imaging (DWI) was performed in 48 non-sedated 3rd trimester fetuses with normal structural MR imaging results. ADC was measured in white matter (frontal, parietal, temporal, and occipital lobes), basal ganglia, thalamus, pons, and cerebellum. Regional ADC values were compared by one-way ANOVA with gestational age as covariate. Regression analysis was used to examine gestational age-related changes in regional ADC. Four other cases of CMV infection were also examined.


Median gestational age was 32 weeks (range, 26–33 weeks). There was a highly significant effect of region on ADC, whereby ADC values were highest in white matter, with significantly lower values in basal ganglia and cerebellum and the lowest values in thalamus and pons. ADC did not significantly change with gestational age in any of the regions tested. In the four cases with fetal CMV infection, ADC value was associated with a global decrease.


ADC values in normal fetal brain are relatively stable during the third trimester, show consistent regional variation, and can make an important contribution to the early diagnosis and possibly prognosis of fetal brain pathologies.


Fetus Brain MRI DWI ADC 


Ethical standards and patient consent

We declare that all human and animal studies have been approved by the Institutional Review Board and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that patient consent was waived in this study.

Conflict of interest

We declare that we have no conflict of interest.


  1. 1.
    Righini A, Bianchini E, Parazzini C, Gementi P, Ramenghi L, Baldoli C, Nicolini U, Mosca F, Triulzi F (2003) Apparent diffusion coefficient determination in normal fetal brain: a prenatal MR imaging study. AJNR Am J Neuroradiol 24(5):799–804PubMedGoogle Scholar
  2. 2.
    Schneider JF, Confort-Gouny S, Le Fur Y, Viout P, Bennathan M, Chapon F, Fogliarini C, Cozzone P, Girard N (2007) Diffusion-weighted imaging in normal fetal brain maturation. Eur Radiol 17(9):2422–2429. doi: 10.1007/s00330-007-0634-x PubMedCrossRefGoogle Scholar
  3. 3.
    Cannie M, De Keyzer F, Meersschaert J, Jani J, Lewi L, Deprest J, Dymarkowski S, Demaerel P (2007) A diffusion-weighted template for gestational age-related apparent diffusion coefficient values in the developing fetal brain. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 30(3):318–324. doi: 10.1002/uog.4078 CrossRefGoogle Scholar
  4. 4.
    Manganaro L, Perrone A, Savelli S, Di Maurizio M, Maggi C, Ballesio L, Porfiri LM, De Felice C, Marinoni E, Marini M (2007) Evaluation of normal brain development by prenatal MR imaging. Radiol Med 112(3):444–455. doi: 10.1007/s11547-007-0153-5 PubMedCrossRefGoogle Scholar
  5. 5.
    Huppi PS, Maier SE, Peled S, Zientara GP, Barnes PD, Jolesz FA, Volpe JJ (1998) Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging. Pediatr Res 44(4):584–590. doi: 10.1203/00006450-199810000-00019 PubMedCrossRefGoogle Scholar
  6. 6.
    Neil JJ, Shiran SI, McKinstry RC, Schefft GL, Snyder AZ, Almli CR, Akbudak E, Aronovitz JA, Miller JP, Lee BC, Conturo TE (1998) Normal brain in human newborns: apparent diffusion coefficient and diffusion anisotropy measured by using diffusion tensor MR imaging. Radiology 209(1):57–66. doi: 10.1148/radiology.209.1.9769812 PubMedCrossRefGoogle Scholar
  7. 7.
    Tanner SF, Ramenghi LA, Ridgway JP, Berry E, Saysell MA, Martinez D, Arthur RJ, Smith MA, Levene MI (2000) Quantitative comparison of intrabrain diffusion in adults and preterm and term neonates and infants. AJR Am J Roentgenol 174(6):1643–1649. doi: 10.2214/ajr.174.6.1741643 PubMedCrossRefGoogle Scholar
  8. 8.
    Miller SP, Vigneron DB, Henry RG, Bohland MA, Ceppi-Cozzio C, Hoffman C, Newton N, Partridge JC, Ferriero DM, Barkovich AJ (2002) Serial quantitative diffusion tensor MRI of the premature brain: development in newborns with and without injury. J Magn Reson Imaging JMRI 16(6):621–632. doi: 10.1002/jmri.10205 CrossRefGoogle Scholar
  9. 9.
    Hoffmann C, Grossman R, Bokov I, Lipitz S, Biegon A (2010) Effect of cytomegalovirus infection on temporal lobe development in utero: quantitative MRI studies. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol 20(12):848–854. doi: 10.1016/j.euroneuro.2010.08.006 CrossRefGoogle Scholar
  10. 10.
    Mailath-Pokorny M, Kasprian G, Mitter C, Schopf V, Nemec U, Prayer D (2012) Magnetic resonance methods in fetal neurology. Semin Fetal Neonatal Med 17(5):278–284. doi: 10.1016/j.siny.2012.06.002 PubMedCrossRefGoogle Scholar
  11. 11.
    Maas LC, Mukherjee P, Carballido-Gamio J, Veeraraghavan S, Miller SP, Partridge SC, Henry RG, Barkovich AJ, Vigneron DB (2004) Early laminar organization of the human cerebrum demonstrated with diffusion tensor imaging in extremely premature infants. NeuroImage 22(3):1134–1140. doi: 10.1016/j.neuroimage.2004.02.035 PubMedCrossRefGoogle Scholar
  12. 12.
    Boyer AC, Goncalves LF, Lee W, Shetty A, Holman A, Yeo L, Romero R (2013) Magnetic resonance diffusion-weighted imaging: reproducibility of regional apparent diffusion coefficients for the normal fetal brain. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 41(2):190–197. doi: 10.1002/uog.11219 CrossRefGoogle Scholar
  13. 13.
    Vasung L, Huang H, Jovanov-Milosevic N, Pletikos M, Mori S, Kostovic I (2010) Development of axonal pathways in the human fetal fronto-limbic brain: histochemical characterization and diffusion tensor imaging. J Anat 217(4):400–417. doi: 10.1111/j.1469-7580.2010.01260.x PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Schneider MM, Berman JI, Baumer FM, Glass HC, Jeng S, Jeremy RJ, Esch M, Biran V, Barkovich AJ, Studholme C, Xu D, Glenn OA (2009) Normative apparent diffusion coefficient values in the developing fetal brain. AJNR Am J Neuroradiol 30(9):1799–1803. doi: 10.3174/ajnr.A1661 PubMedCrossRefGoogle Scholar
  15. 15.
    Ramenghi LA, Martinelli A, De Carli A, Brusati V, Mandia L, Fumagalli M, Triulzi F, Mosca F, Cetin I (2011) Cerebral maturation in IUGR and appropriate for gestational age preterm babies. Reprod Sci 18(5):469–475. doi: 10.1177/1933719110388847 PubMedCrossRefGoogle Scholar
  16. 16.
    Weidenheim KM, Epshteyn I, Rashbaum WK, Lyman WD (1993) Neuroanatomical localization of myelin basic protein in the late first and early second trimester human foetal spinal cord and brainstem. J Neurocytol 22(7):507–516PubMedCrossRefGoogle Scholar
  17. 17.
    Weidenheim KM, Bodhireddy SR, Rashbaum WK, Lyman WD (1996) Temporal and spatial expression of major myelin proteins in the human fetal spinal cord during the second trimester. J Neuropathol Exp Neurol 55(6):734–745PubMedCrossRefGoogle Scholar
  18. 18.
    Huppi PS, Dubois J (2006) Diffusion tensor imaging of brain development. Semin Fetal Neonatal Med 11(6):489–497. doi: 10.1016/j.siny.2006.07.006 PubMedCrossRefGoogle Scholar
  19. 19.
    Marks MP, de Crespigny A, Lentz D, Enzmann DR, Albers GW, Moseley ME (1996) Acute and chronic stroke: navigated spin-echo diffusion-weighted MR imaging. Radiology 199(2):403–408. doi: 10.1148/radiology.199.2.8668785 PubMedCrossRefGoogle Scholar
  20. 20.
    Desai V, Shen Q, Duong TQ (2012) Incorporating ADC temporal profiles to predict ischemic tissue fate in acute stroke. Brain Res 1458:86–92. doi: 10.1016/j.brainres.2012.04.004 PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Kralik SF, Taha A, Kamer AP, Cardinal JS, Seltman TA, Ho CY (2013) Diffusion imaging for tumor grading of supratentorial brain tumors in the first year of life. AJNR Am J Neuroradiol. doi: 10.3174/ajnr.A3757 PubMedGoogle Scholar
  22. 22.
    Barajas RF Jr, Rubenstein JL, Chang JS, Hwang J, Cha S (2010) Diffusion-weighted MR imaging derived apparent diffusion coefficient is predictive of clinical outcome in primary central nervous system lymphoma. AJNR Am J Neuroradiol 31(1):60–66. doi: 10.3174/ajnr.A1750 PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Viola A, Confort-Gouny S, Schneider JF, Le Fur Y, Viout P, Chapon F, Pineau S, Cozzone PJ, Girard N (2011) Is brain maturation comparable in fetuses and premature neonates at term equivalent age? AJNR Am J Neuroradiol 32(8):1451–1458. doi: 10.3174/ajnr.A2555 PubMedCrossRefGoogle Scholar
  24. 24.
    Carson MJ, Thrash JC, Walter B (2006) The cellular response in neuroinflammation: the role of leukocytes, microglia and astrocytes in neuronal death and survival. Clin Neurosci Res 6(5):237–245. doi: 10.1016/j.cnr.2006.09.004 PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    van der Voorn JP, Pouwels PJ, Vermeulen RJ, Barkhof F, van der Knaap MS (2009) Quantitative MR imaging and spectroscopy in congenital cytomegalovirus infection and periventricular leukomalacia suggests a comparable neuropathological substrate of the cerebral white matter lesions. Neuropediatrics 40(4):168–173. doi: 10.1055/s-0029-1243228 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Chen Hoffmann
    • 1
    • 4
  • Boaz Weisz
    • 2
  • Shlomo Lipitz
    • 2
  • Gal Yaniv
    • 1
  • Eldad Katorza
    • 2
  • Dafi Bergman
    • 1
  • Anat Biegon
    • 3
  1. 1.Department of Radiology, Sheba Medical Center, Tel Hashomer (affiliated to the Sackler School of Medicine)Tel Aviv UniversityTel AvivIsrael
  2. 2.Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer (affiliated to the Sackler School of Medicine)Tel Aviv UniversityTel AvivIsrael
  3. 3.Department of NeurologyStony Brook University School of MedicineStony BrookUSA
  4. 4.Diagnostic ImagingSheba Medical CenterTel HashomerIsrael

Personalised recommendations