White and gray matter development in human fetal, newborn and pediatric brains Hao Huang, a Jiangyang Zhang, a Setsu Wakana, a,b Weihong Zhang, a,b Tianbo Ren, c Linda J. Richards, d Paul Yarowsky, e Pamela Donohue, f Ernest Graham, g Peter C.M. van Zijl, a,b and Susumu Mori, a,b, ⁎ a Department of Radiology, Johns Hopkins University School of Medicine 720 Rutland Avenue, Baltimore, MD 21205, USA b F.M. Kirby Center for Functional Magnetic Resonance Imaging, Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205, USA c Department of Anatomy and Neurobiology, University of Maryland, 655 West Baltimore Street, Baltimore, MD 21201, USA d Department of Anatomy and Developmental Biology, The University of Queensland, St Lucia, Queensland, 4072, Australia e Department of Pharmacology and Experimental Therapeutics, University of Maryland, 655 West Baltimore Street, Baltimore, MD 21201, USA f Department of Pediatrics, Johns Hopkins University School of Medicine 720 Rutland Avenue, Baltimore, MD 21205, USA g Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine 720 Rutland Avenue, Baltimore, MD 21205, USA Received 29 March 2006; revised 29 May 2006; accepted 6 June 2006 Available online 14 August 2006 Brain anatomy is characterized by dramatic growth from the end of the second trimester through the neonatal stage. The characterization of normal axonal growth of the white matter tracts has not been well- documented to date and could provide important clues to understanding the extensive inhomogeneity of white matter injuries in cerebral palsy (CP) patients. However, anatomical studies of human brain develop- ment during this period are surprisingly scarce and histology-based atlases have become available only recently. Diffusion tensor magnetic resonance imaging (DTMRI) can reveal detailed anatomy of white matter. We acquired diffusion tensor images (DTI) of postmortem fetal brain samples and in vivo neonates and children. Neural structures were annotated in two-dimensional (2D) slices, segmented, measured, and reconstructed three-dimensionally (3D). The growth status of various white matter tracts was evaluated on cross-sections at 19–20 gestational weeks, and compared with 0-month-old neonates and 5- to 6-year-old children. Limbic, commissural, association, and projection white matter tracts and gray matter structures were illustrated in 3D and quanti- tatively characterized to assess their dynamic changes. The overall pattern of the time courses for the development of different white matter is that limbic fibers develop first and association fibers last and commis- sural and projection fibers are forming from anterior to posterior part of the brain. The resultant DTMRI-based 3D human brain data will be a valuable resource for human brain developmental study and will provide reference standards for diagnostic radiology of premature newborns. © 2006 Elsevier Inc. All rights reserved. Keywords: DTI; Brain development; Atlas; Neonate; PVL Introduction It has been shown that diffusion tensor magnetic resonance imaging (DTMRI) can reveal the detailed anatomy of human brain white matter (Basser et al., 1994; Pierpaoli and Basser, 1996; Makris et al., 1997; Stieltjes et al., 2001; Catani et al., 2002; Wakana et al., 2004, Mori et al., 2005). The contrast, which is based on structural alignment, provides unique information about axonal tracts and is difficult to obtain by any other non-invasive technique. This infor- mation is especially useful to delineate the anatomy of premature brain that is not myelinated and for which relaxation-based contrast is inadequate (Huppi et al., 1998; Neil et al., 1998; Mori et al., 2001; McKinstry et al., 2002; Mukherjee et al., 2002; Maas et al., 2004; Partridge et al., 2004; Schneider et al., 2004; Hermoye et al., 2006). The technique can delineate injuries in specific white matter tracts as well as demonstrate the rearrangement of tracts (Huppi and Inderc, 2001; Hoon et al., 2002; Miller et al., 2002; Lee et al., 2005; Thomas et al., 2005). As DTI becomes widely available in clinical scanners, it is likely that DTI will be an important diagnostic tool in this field in the future. Among pediatric cases, imaging of pre- or full-term infants for clinical indications is of great interest. Routinely used diagnostic methods, such as electronic monitoring and ultrasound, often have poor sensitivity to significant abnormalities in neonate brains. A new imaging modality that can precisely delineate anatomical and physiological abnormalities is urgently needed. Furthermore, it has been demonstrated that various injuries, due to perinatal risks, often lead to damage in selective white matter. Precise delineation of the status of specific white matter tracts may provide more accurate diagnosis. Because of the advances in the critical care of pre-term infants, the survival rate of premature infants has increased dramatically in recent years. Identification of abnorm- alities in the early phase of injuries, identification of perinatal risk www.elsevier.com/locate/ynimg NeuroImage 33 (2006) 27 – 38 Abbreviations: CP, cerebral palsy; DT, diffusion tensor; MRI, magnetic resonance imaging; 2D/3D, two/three dimensional. ⁎ Corresponding author. Johns Hopkins University School of Medicine, Department of Radiology, 217 Traylor Building, 720 Rutland Avenue, Baltimore, MD 21205, USA. Fax: +1 410 614 1948. E-mail address: Susumu@mri.jhu.edu (S. Mori). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2006.06.009