PEDIATRICS Vol. 122 No. 3 September 2008, pp. 656-657 (doi:10.1542/peds.2008-1604)
COMMENTARY |
Diffusion Tensor Imaging of White Matter and Developmental Outcome
Departments of Neurology, Pediatrics, and Physical Medicine and Rehabilitation, Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, Maryland
Abbreviations: CP, cerebral palsy • DTI, diffusion tensor imaging • FA, fractional anisotropy • ADC, apparent diffusion coefficient
MRI of the brain has become a valuable tool for determining the cause of cerebral palsy (CP) in patients as well as for research on the diverse mechanisms that are responsible for its pathogenesis.1 MRI is far superior to other forms of brain imaging, such as computerized axial tomography (CAT) scanning, for evaluating patients with CP, because it dramatically enhances the contrast between white and gray matter. The multicenter European Cerebral Palsy Study reported that 88% of 351 children with CP imaged at a mean age of 38 months had lesions that appeared on MRI.2 These included 43% with white matter damage associated with immaturity, 13% with basal ganglia damage, 9% with malformations, 9% with cortical damage, and 7% with focal infarcts. MRI evidence of white matter injury was strongly associated with spastic diplegia or quadriplegia, whereas lesions in the basal ganglia or focal infarcts were associated with the dystonic or hemiplegic forms of CP, respectively. Eighty percent of the children with white matter injury were born prematurely before 34 weeks' gestation. Although the rest of the children with white matter injury were born later in gestation, most had prenatal risk factors such as infection that suggested that their injury had also occurred before 34 weeks.1 These data underline the importance of understanding the pathogenesis of this diverse group of pathologies, especially disorders of developing white matter.
Recent advances in a magnetic-resonance technique called diffusion tensor imaging (DTI) are making it possible to evaluate lesions in specific white matter tracts in the brain and provide quantitative data on their physical integrity.3 DTI uses diffusion-weighted sequences that are sensitive to the movement of protons in brain water, similar to those used clinically for the rapid diagnosis of stroke and edema. Because axons and their myelin coverings in white matter run lengthwise next to each other like wires in a cable, water molecules diffuse easily in the direction parallel to their length but are unable to diffuse freely at right angles to them. The imaging sequences used in DTI can detect the diffusion of water in 6 to 32 directions in each voxel (cube) of tissue, many more than used in conventional diffusion-weighted imaging, which makes it possible to resolve small changes in the direction of fibers and create detailed maps through a process called tractography. DTI data can also be used to calculate numerical variables that describe water diffusion in each voxel within individual white matter pathways. The degree to which water is restricted in its movement by anatomic structures is described by the term fractional anisotropy (FA), which has values ranging from 0 to 1. A value of 0 indicates free movement of water in all directions in the shape of a sphere (isotropic diffusion), and a value of 1 describes the state in which diffusion is restricted within the shape of a cylinder (anisotropic diffusion). FA values close to 1 in white matter pathways indicate predominant movement of water in an ellipsoid space parallel to axons. These high values suggest greater integrity or organization within the white matter, whereas low FA values suggest damage or immaturity of white matter. The average freedom of diffusion of water molecules in each voxel can also be calculated as the apparent diffusion coefficient (ADC) or the directionally averaged mean diffusivity (Dav). These methods have been used to examine normal white matter development4 and assess abnormalities in preterm infants5 and older patients with CP.6
In their article in this issue of Pediatrics, Murakami et al7 used these DTI fiber-tracking methods to measure FA in the corticospinal tract in a group of 10 infants aged 9 to 41 months. These children were born preterm with documented episodes of hypoxia, and all had imaging findings consistent with periventricular leukomalacia. However, when evaluations of motor function were performed at 15 to 63 months of age, 5 were judged to have spastic diplegia or quadriplegia, and half did not have CP. The children with CP tended to have FA values of <0.5, whereas those with less disability had values of >0.5, suggesting that a cutoff value for FA of <0.5 may be useful for predicting periventricular leukomalacia that is severe enough to produce a severe motor disability. They found that estimation of FA using the fiber-tracking method to identify the corticospinal tract was more sensitive to differences in motor outcome than using a region of interest based on anatomic landmarks. Although the study was based on a small group of patients, its results suggest that DTI with tractography might be useful for determining prognosis and need for early intervention. The data are consistent with several other recent reports on the relationship between early DTI data and outcome. For example, Arzoumanian et al8 and Drobyshevsky et al9 reported that low FA and high ADC values in white matter using region-of-interest measurements was associated with motor impairment in a group of premature infants at 2 years of age. Yung et al10 also found that whole-brain white matter volume and reduced FA values were associated with impaired cognitive outcome. Krishnan et al11 found that there was a negative correlation between mean ADC in white matter of preterm infants and developmental quotient at 2 years' corrected age. These results suggest that DTI of white matter will be useful for developmental follow-up studies as the methodology becomes more widely available for routine use.
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FOOTNOTES |
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Accepted Jun 3, 2008.
Address correspondence to Michael V. Johnston, MD, Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Departments of Neurology, Pediatrics, and Physical Medicine and Rehabilitation, 707 N Broadway, Baltimore, MD 21205. E-mail: johnston{at}kennedykrieger.org
The author has indicated he has no financial relationships relevant to this article to disclose.
Opinions expressed in these commentaries are those of the author and not necessarily those of the American Academy of Pediatrics or its Committees.
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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
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