, Volume 10, Issue 2, pp 173–180 | Cite as

Optimizing Hippocampal Segmentation in Infants Utilizing MRI Post-Acquisition Processing

  • Deanne K. Thompson
  • Zohra M. Ahmadzai
  • Stephen J. Wood
  • Terrie E. Inder
  • Simon K. Warfield
  • Lex W. Doyle
  • Gary F. Egan
Original Article


This study aims to determine the most reliable method for infant hippocampal segmentation by comparing magnetic resonance (MR) imaging post-acquisition processing techniques: contrast to noise ratio (CNR) enhancement, or reformatting to standard orientation. MR scans were performed with a 1.5 T GE scanner to obtain dual echo T2 and proton density (PD) images at term equivalent (38–42 weeks’ gestational age). 15 hippocampi were manually traced four times on ten infant images by 2 independent raters on the original T2 image, as well as images processed by: a) combining T2 and PD images (T2-PD) to enhance CNR; then b) reformatting T2-PD images perpendicular to the long axis of the left hippocampus. CNRs and intraclass correlation coefficients (ICC) were calculated. T2-PD images had 17% higher CNR (15.2) than T2 images (12.6). Original T2 volumes’ ICC was 0.87 for rater 1 and 0.84 for rater 2, whereas T2-PD images’ ICC was 0.95 for rater 1 and 0.87 for rater 2. Reliability of hippocampal segmentation on T2-PD images was not improved by reformatting images (rater 1 ICC = 0.88, rater 2 ICC = 0.66). Post-acquisition processing can improve CNR and hence reliability of hippocampal segmentation in neonate MR scans when tissue contrast is poor. These findings may be applied to enhance boundary definition in infant segmentation for various brain structures or in any volumetric study where image contrast is sub-optimal, enabling hippocampal structure-function relationships to be explored.


Neonate Preterm Magnetic resonance imaging Volume Hippocampus Brain 



The authors gratefully thank Merilyn Bear, Michael Kean, Katherine Lee, Gregory A. Lodygensky, Hong X. Wang, Michael J.Farrell, Peter J. Anderson, and Rodney W. Hunt, the VIBeS and Developmental Imaging teams at the Murdoch Childrens Research Institute, as well as the families and infants who participated in this study.

Grant sponsors

National Medical and Health Research Council of Australia; Grant number: 237117; Grant sponsor: NIH; Grant number: R01 RR021885, R01 GM074068, R01 EB008015, P30 HD018655; Grant sponsor: NHMRC Research Fellowship; Grant number: 400317; Grant sponsors: United Cerebral Palsy Foundation (USA), Mather Foundation (USA), Brown Foundation (USA), NHMRC Clinical Career Development Award, NARSAD Young Investigator Award, Victorian Government’s Operational Infrastructure Support Program.


  1. Abernethy, L. J., Palaniappan, M., & Cooke, R. W. (2002). Quantitative magnetic resonance imaging of the brain in survivors of very low birth weight. Archives of Disease in Childhood, 87(4), 279–283.PubMedCrossRefGoogle Scholar
  2. Abernethy, L. J., Cooke, R. W. I., & Foulder-Hughes, L. (2004). Caudate and hippocampal volumes, intelligence, and motor impairment in 7-year-old children who were born preterm. Pediatric Research, 55(5), 884–893.PubMedCrossRefGoogle Scholar
  3. Bartzokis, G., Altshuler, L. L., Greider, T., Curran, J., Keen, B., & Dixon, W. J. (1998). Reliability of medial temporal lobe volume measurements using reformatted 3D images. Psychiatry Research, 82(1), 11–24.PubMedCrossRefGoogle Scholar
  4. Bergouignan, L., Chupin, M., Czechowska, Y., Kinkingnehun, S., Lemogne, C., Le Bastard, G., et al. (2009). Can voxel based morphometry, manual segmentation and automated segmentation equally detect hippocampal volume differences in acute depression? NeuroImage, 45(1), 29–37.PubMedCrossRefGoogle Scholar
  5. Bridle, N., Pantelis, C., Wood, S. J., Coppola, R., Velakoulis, D., McStephen, M., et al. (2002). Thalamic and caudate volumes in monozygotic twins discordant for schizophrenia. Australian and New Zealand Journal of Psychiatry, 36(3), 347–354.PubMedCrossRefGoogle Scholar
  6. Conklin, J., Winter, J. D., Thompson, R. T., & Gelman, N. (2008). High-contrast 3D neonatal brain imaging with combined T1- and T2-weighted MP-RAGE. Magnetic Resonance in Medicine, 59(5), 1190–1196.PubMedCrossRefGoogle Scholar
  7. Duvernoy, H. M. (1988). The human Hippocampus. An atlas of applied anatomy. Munchen: J. F. Bergmann Verlag.Google Scholar
  8. Geuze, E., Vermetten, E., & Bremner, J. D. (2005a). MR-based in vivo hippocampal volumetrics: 1. Review of methodologies currently employed. Molecular Psychiatry, 10(2), 147–159.Google Scholar
  9. Geuze, E., Vermetten, E., & Bremner, J. D. (2005b). MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Molecular Psychiatry, 10(2), 160–184.CrossRefGoogle Scholar
  10. Hasboun, D., Chantome, M., Zouaoui, A., Sahel, M., Deladoeuille, M., Sourour, N., et al. (1996). MR determination of hippocampal volume: Comparison of three methods. American Journal of Neuroradiology, 17(6), 1091–1098.PubMedGoogle Scholar
  11. Jack, C., Jr., Bentley, M., Twomey, C., & Zinsmeister, A. (1990). MR imaging-based volume measurements of the hippocampal formation and anterior temporal lobe: validation studies. Radiology, 176(1), 205–209.PubMedGoogle Scholar
  12. Jack, C. R., Jr., Theodore, W. H., Cook, M., & McCarthy, G. (1995). MRI-based hippocampal volumetrics: data acquisition, normal ranges, and optimal protocol. Magnetic Resonance Imaging, 13(8), 1057–1064.PubMedCrossRefGoogle Scholar
  13. Jeukens, C. R., Vlooswijk, M. C., Majoie, H. J., de Krom, M. C., Aldenkamp, A. P., Hofman, P. A., et al. (2009). Hippocampal MRI volumetry at 3 Tesla: reliability and practical guidance. Investigative Radiology, 44(9), 509–517.PubMedCrossRefGoogle Scholar
  14. Klauschen, F., Goldman, A., Barra, V., Meyer-Lindenberg, A., & Lundervold, A. (2009). Evaluation of automated brain MR image segmentation and volumetry methods. Human Brain Mapping, 30(4), 1310–1327.PubMedCrossRefGoogle Scholar
  15. Konrad, C., Ukas, T., Nebel, C., Arolt, V., Toga, A. W., & Narr, K. L. (2009). Defining the human hippocampus in cerebral magnetic resonance images–an overview of current segmentation protocols. NeuroImage, 47(4), 1185–1195.PubMedCrossRefGoogle Scholar
  16. Kretschmann, H. J., Kammradt, G., Krauthausen, I., Sauer, B., & Wingert, F. (1986). Growth of the hippocampal formation in man. Bibliotheca Anatomica, 28, 27–52.PubMedGoogle Scholar
  17. Lim, K. O., & Pfefferbaum, A. (1989). Segmentation of MR brain images into cerebrospinal fluid spaces, white and grey matter. Journal of Computer Assisted Tomography, 13, 588–593.PubMedCrossRefGoogle Scholar
  18. Lodygensky, G. A., Rademaker, K., Zimine, S., Gex-Fabry, M., Lieftink, A. F., Lazeyras, F., et al. (2005). Structural and functional brain development after hydrocortisone treatment for neonatal chronic lung disease. Pediatrics, 116(1), 1–7.PubMedCrossRefGoogle Scholar
  19. Lodygensky, G. A., Seghier, M. L., Warfield, S. K., Tolsa, C. B., Sizonenko, S., Lazeyras, F., et al. (2008). Intrauterine growth restriction affects the preterm infant’s hippocampus. Pediatric Research, 63(4), 438–443.PubMedCrossRefGoogle Scholar
  20. Mai, J. K., Assheuer, J., & Paxinos, G. (1997). Atlas of the human brain. San Diego: Academic.Google Scholar
  21. Malykhin, N. V., Bouchard, T. P., Ogilvie, C. J., Coupland, N. J., Seres, P., & Camicioli, R. (2007). Three-dimensional volumetric analysis and reconstruction of amygdala and hippocampal head, body and tail. Psychiatry Research, 155(2), 155–165.PubMedCrossRefGoogle Scholar
  22. Naidich, T. P., Daniels, D. L., Haughton, V. M., Williams, A., Pojunas, K., & Palacios, E. (1987). Hippocampal formation and related structures of the limbic lobe: anatomic-MR correlation. Part I. Surface features and coronal sections. Radiology, 162(3), 747–754.PubMedGoogle Scholar
  23. Obenaus, A., Yong-Hing, C. J., Tong, K. A., & Sarty, G. E. (2001). A reliable method for measurement and normalization of pediatric hippocampal volumes. Pediatric Research, 50(1), 124–132.PubMedCrossRefGoogle Scholar
  24. Pantel, J., O’Leary, D. S., Cretsinger, K., Bockholt, H. J., Keefe, H., Magnotta, V. A., et al. (2000). A new method for the in vivo volumetric measurement of the human hippocampus with high neuroanatomical accuracy. Hippocampus, 10(6), 752–758.PubMedCrossRefGoogle Scholar
  25. Patwardhan, A. J., Eliez, S., Warsofsky, I. S., Glover, G. H., White, C. D., Giedd, J. N., et al. (2001). Effects of image orientation on the comparability of pediatric brain volumes using three-dimensional MR data. Journal of Computer Assisted Tomography, 25(3), 452–457.PubMedCrossRefGoogle Scholar
  26. Peterson, B. S., Vohr, B., Staib, L. H., Cannistraci, C. J., Dolberg, A., Schneider, K. C., et al. (2000). Regional brain volume abnormalities and long-term cognitive outcome in preterm infants. Journal of the American Medical Association, 284(15), 1939–1947.PubMedCrossRefGoogle Scholar
  27. Saitoh, O., Karns, C. M., & Courchesne, E. (2001). Development of the hippocampal formation from 2 to 42 years: MRI evidence of smaller area dentata in autism. Brain, 124(Pt 7), 1317–1324.PubMedCrossRefGoogle Scholar
  28. Schuff, N., Woerner, N., Boreta, L., Kornfield, T., Shaw, L. M., Trojanowski, J. Q., et al. (2009). MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype and biomarkers. Brain, 132(Pt 4), 1067–1077.PubMedGoogle Scholar
  29. Thompson, D. K., Wood, S. J., Doyle, L. W., Warfield, S. K., Lodygensky, G. A., Anderson, P. J., et al. (2008). Neonate hippocampal volumes: Prematurity, perinatal predictors, and 2-year outcome. Annals of Neurology, 63(5), 642–651.PubMedCrossRefGoogle Scholar
  30. Thompson, D. K., Wood, S. J., Doyle, L. W., Warfield, S. K., Egan, G. F., & Inder, T. E. (2009). MR-determined hippocampal asymmetry in full-term and preterm neonates. Hippocampus, 19(2), 118–123.PubMedCrossRefGoogle Scholar
  31. Vannier, M. W., Butterfield, R. L., Jordan, D., Murphy, W. A., Levitt, R. G., & Gado, M. (1985). Multispectral analysis of magnetic resonance images. Radiology, 154(1), 221–224.PubMedGoogle Scholar
  32. Watson, C., Andermann, F., Gloor, P., Jonesgotman, M., Peters, T., Evans, A., et al. (1992). Anatomic Basis of Amygdaloid and Hippocampal Volume Measurement by Magnetic-Resonance-Imaging. Neurology, 42(9), 1743–1750.PubMedGoogle Scholar
  33. Wieshmann, U. C., Free, S. L., Stevens, J. M., & Shorvon, S. D. (1998). Image contrast and hippocampal volumetric measurements. Magnetic Resonance Imaging, 16(1), 13–17.PubMedCrossRefGoogle Scholar
  34. Williams, L. A., Gelman, N., Picot, P. A., Lee, D. S., Ewing, J. R., Han, V. K., et al. (2005). Neonatal brain: regional variability of in vivo MR imaging relaxation rates at 3.0T–initial experience. Radiology, 235(2), 595–603.PubMedCrossRefGoogle Scholar
  35. Williams, L. A., DeVito, T. J., Winter, J. D., Orr, T. N., Thompson, R. T., & Gelman, N. (2007). Optimization of 3D MP-RAGE for neonatal brain imaging at 3.0T. Magnetic Resonance Imaging, 25(8), 1162–1170.PubMedCrossRefGoogle Scholar
  36. Wu, W. C., Huang, C. C., Chung, H. W., Liou, M., Hsueh, C. J., Lee, C. S., et al. (2005). Hippocampal alterations in children with temporal lobe epilepsy with or without a history of febrile convulsions: evaluations with MR volumetry and proton MR spectroscopy. American Journal of Neuroradiology, 26(5), 1270–1275.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Deanne K. Thompson
    • 1
    • 2
  • Zohra M. Ahmadzai
    • 1
  • Stephen J. Wood
    • 3
    • 4
  • Terrie E. Inder
    • 1
    • 5
  • Simon K. Warfield
    • 6
  • Lex W. Doyle
    • 1
    • 7
  • Gary F. Egan
    • 2
    • 8
  1. 1.Critical Care and NeurosciencesMurdoch Childrens Research Institute, Royal Children’s HospitalMelbourneAustralia
  2. 2.Centre for NeuroscienceFlorey Neuroscience Institutes, University of MelbourneMelbourneAustralia
  3. 3.Department of PsychiatryMelbourne Neuropsychiatry Centre and Melbourne Health, University of MelbourneMelbourneAustralia
  4. 4.School of PsychologyUniversity of BirminghamBirminghamUK
  5. 5.Department of PediatricsSt Louis Children’s Hospital, Washington University in St LouisSt LouisUSA
  6. 6.Department of RadiologyChildren’s Hospital, Harvard Medical SchoolBostonUSA
  7. 7.Department of Obstetrics and GynecologyRoyal Women’s Hospital, University of MelbourneMelbourneAustralia
  8. 8.Monash Biomedical ImagingMonash UniversityMelbourneAustralia

Personalised recommendations