Diffusion tensor imaging detects abnormalities in the corticospinal tracts of neonates with infantile Krabbe disease

Abstract

Background and purpose: It is not possible to determine if neonates diagnosed with Krabbe disease through statewide neonate screening programs will develop the disease as infants, juveniles, or adults. The only available treatment for this fatal neurodegenerative condition is unrelated umbilical cord transplantation, but this treatment is only effective before clinical symptoms appear. Therefore, a marker of disease progression is needed. The purpose of this study was to evaluate the use of diffusion tensor imaging (DTI) with fiber tracking in identifying early changes in major motor tracts of asymptomatic neonates with infantile Krabbe disease.

Materials and methods: Six neonates with infantile Krabbe disease identified because of family history underwent brain MR imaging within the first 4 weeks of life. Six-direction DTI and quantitative tractography of the corticospinal tracts were performed. Hypothesis tests, 1 for each hemisphere, were used to determine whether the fractional anisotropy (FA) ratio of the neonates with infantile Krabbe disease was significantly different from that of 45 age- and sex-matched controls.

Results: The average FA ratio for patients with Krabbe disease was 0.89 and 0.87 for left and right tracts, respectively (P = .002 and < .001). After adjusting for gestational age, gestational age at birth, birth weight, sex, and race, the 6 patients with Krabbe disease had significantly lower FA values than the controls (P < .001).

Conclusions: DTI with quantitative tractography detected significant differences in the corticospinal tracts of asymptomatic neonates who had the early-onset form of Krabbe disease. Once standardized and validated, this tool has the potential to be used as a marker of disease progression in neonates diagnosed through statewide neonate screening programs.

Figures

Fig 1.

Visualization of DTI fiber tracts through the right hemispheric internal capsule with FA coloring of the fibers from a lateral viewpoint. Top row: 5 representative control subjects. Bottom row: 4 selected Krabbe subjects. Visually, all Krabbe subjects show lower FA values along most of the fiber bundle than any of the controls.

Fig 2.

Raw FA mean values for patients with infantile Krabbe disease and controls. Each point represents a child's mean FA across the central portion of the corticospinal tract. The red triangles represent the 6 patients with Krabbe disease, whereas the blue diamonds show the typical controls. The red and blue lines represent the linear trend related to corrected age at the time of the MR imaging.

Fig 3.

Normalized FA ratios for patients with infantile Krabbe disease and controls. The FA ratio is the observed FA divided by the expected FA. given the child's gestational age at birth, corrected age at scanning, birth weight, and sex. The red triangles represent the 6 patients with Krabbe disease, whereas the blue diamonds show the typical controls. The horizontal black lines represent the SDs based on the controls.