Pediatric diffusion tensor imaging: Normal database and observation of the white matter maturation in early childhood
Introduction
MRI plays a crucial role in the radiological diagnosis of pediatric brain pathologies. However, anatomical evaluation of the brain in the early phases of development is challenging. In the first 24 months after birth, the brain undergoes considerable anatomical changes, which significantly influence MR relaxation parameters. In newborn brains, the T1 and T2 of the cell-dense gray matter are shorter than those of white matter, but, after myelination, the contrast inverts (Barkovich et al., 1988). During this contrast transition period, MRI may even fail to differentiate between gray and white matter.
Recently, it has been shown that DTI, in which the contrast is based on structural alignment, provides more stable anatomical contrasts in pediatric brains (Baratti et al., 1999, Dubois et al., 2004, Huppi and Inder, 2001, Maas et al., 2004, McKinstry et al., 2002a, Mori et al., 2001, Mukherjee et al., 2002, Neil et al., 1998, Partridge et al., 2004, Schneider et al., 2004). DTI can differentiate not only gray and white matter but can also reveal the anatomy of the white matter tracts in newborn brains (Berman et al., 2004). DTI has already shown promising results in the study of various developmental brain diseases, such as periventricular leukomalacia (Hoon et al., 2002, Huppi et al., 2001), holoprosencephaly (Albayram et al., 2002), callosal dysgenesis (Lee et al., 2004b), focal cortical dysplasia (Lee et al., 2004a), perinatal brain injury (Huppi et al., 2001, McKinstry et al., 2002b), tumor (Gauvain et al., 2001), and developmental delay (Filippi et al., 2003). While the potential of DTI as a new diagnostic tool for pediatric brain imaging is undoubtedly high, it is also true that pediatric DTI studies have a unique shortcoming, namely, the lack of normal data.
Because of its high sensitivity to motion, DTI of children under 4 years of age requires sedation, which is not permitted in healthy volunteers in most countries. Whereas newborns (0 month) can be scanned while sleeping, this becomes increasingly difficult as children get older and more alert. As a result, normal DTI data for the pediatric brain are scarce, although such data are essential for neuroradiologists to differentiate normal from abnormal cases.
The goal of this study is to provide the radiological, neurological, and pediatric communities with a standard of reference for the clinical interpretation of pediatric DTI images. This collection of normal data was made possible by a multi-institutional collaboration, in which a common DTI protocol was established, tested, and used at three participating sites. To increase the accessibility of this database, a web site has been created at which the DTI images can be visualized and from which they can be downloaded.
Section snippets
Subjects
Seven healthy pediatric volunteers and 23 pediatric patients referred for a clinical MR examination were included in the study (17 boys, 13 girls; mean age: 16 ± 16 months; age range: 0–54 months; Fig. 1). The clinical indications were pathologies related to the internal ear (n = 6), the orbits (n = 3), the spine (n = 3), fit (n = 6), trauma (n = 1), infectious disease (n = 1), genetic disease (n = 1), and vascular/cisternal malformation (n = 2). There were 24 children classified as white and 6
Overview of developing brains
The evolution of the DTI color maps is depicted in Fig. 2. Because the most significant changes occur during the first year of life, representative color maps are shown every 3 months during this period and every year in older children. The two last columns are an adult reference. Throughout the entire age range (0–54 months), high-quality color maps could be obtained. Almost all prominent white matter tracts could be identified from birth, although they appeared thinner and the FA was lower.
Potential of DTI for anatomical imaging in infants and the need for normal databases
Although MRI has been an essential tool for studying the pathology of pediatric brains, the amount of anatomical information it can offer has often been limited due to rapid contrast changes in the early phases of development. In pre-myelinated brains or during the myelination process, gray and white matter often have similar T1 and T2 relaxation times, which leads to poor anatomical contrast. As previously reported by Miller et al. (2003) and also as seen in Fig. 2, DTI, even at birth, can
Conclusions
In conclusion, the reference images presented in this paper and the online database can pave the way for the use of diffusion tensor imaging in the diagnosis of pediatric pathologies, most notably developmental abnormalities, tumors, and white matter diseases. In the past, there were several factors that hindered the application of DTI to pediatric studies, including the long scanning time, a low SNR that precluded the high resolution imaging required for small brains, and the scarcity of
Acknowledgments
This study was supported by NIH grants RO1 AG20012, P41 RR15241, and R21-EB000991. Dr. van Zijl is a paid lecturer for Philips Medical Systems. This arrangement has been approved by Johns Hopkins University in accordance with its conflict of interest policies.
References (44)
- et al.
Estimation of the effective self-diffusion tensor from the NMR spin echo
J. Magn. Reson., Ser. B
(1994) - et al.
Magnetic resonance techniques in the evaluation of the perinatal brain: recent advances and future directions
Semin. Neonatol.
(2001) - et al.
Diffusion tensor MRI visualizes decreased subcortical fiber connectivity in focal cortical dysplasia
NeuroImage
(2004) - et al.
Early laminar organization of the human cerebrum demonstrated with diffusion tensor imaging in extremely premature infants
NeuroImage
(2004) - et al.
Diffusion tensor imaging: serial quantitation of white matter tract maturity in premature newborns
NeuroImage
(2004) - et al.
Maturation of white matter in the human brain: a review of magnetic resonance studies
Brain Res. Bull.
(2001) - et al.
Three-dimensional anatomical characterization of the developing mouse brain by diffusion tensor microimaging
NeuroImage
(2003) - et al.
Holoprosencephaly in children: diffusion tensor MR imaging of white matter tracts of the brainstem—Initial experience
Radiology
(2002) - et al.
Analysis of partial volume effects in diffusion-tensor MRI
Magn. Reson. Med.
(2001) - et al.
Improved diffusion-weighted single-shot echo-planar imaging (EPI) in stroke using sensitivity encoding (SENSE)
Magn. Reson. Med.
(2001)
Comparative MR imaging study of brain maturation in kittens with T1, T2, and the trace of the diffusion tensor
Radiology
Normal maturation of the neonatal and infant brain: MR imaging at 1.5 T
Radiology
The basis of anisotropic water diffusion in the nervous system—A technical review
NMR Biomed.
Determinants of anisotropic water diffusion in nerves
Magn. Reson. Med.
Quantitative DTI fiber tracking of white matter pathways in premature newborns
Proc. Int. Soc. Mag. Reson. Med.
Sequence of central nervous system myelination in human infancy. I. An autopsy study of myelination
J. Neuropathol. Exp. Neurol.
Tracking healthy babies' white matter fibers despite low anisotropy: a feasibility study
Proc. Int. Soc. Mag. Reson. Med.
Diffusion-tensor MR imaging in children with developmental delay: preliminary findings
Radiology
Evaluating pediatric brain tumor cellularity with diffusion-tensor imaging
Am. J. Roentgenol.
Diffusion tensor imaging of periventricular leukomalacia shows affected sensory cortex white matter pathways
Neurology
Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging
Pediatrics
Cited by (354)
Diffusion tensor imaging in pediatric patients with dystonia
2024, NeuroImageMapping the evolution of regional brain network efficiency and its association with cognitive abilities during the first twenty-eight months of life
2023, Developmental Cognitive NeuroscienceMusic impacts brain cortical microstructural maturation in very preterm infants: A longitudinal diffusion MR imaging study
2023, Developmental Cognitive NeuroscienceProtracted development of motor cortex constrains rich interpretations of infant cognition
2023, Trends in Cognitive Sciences