Assessing disease severity in late infantile neuronal ceroid lipofuscinosis using quantitative MR diffusion-weighted imaging

Abstract

Background and purpose: Late infantile neuronal ceroid lipofuscinosis (LINCL), a form of Batten disease, is a fatal neurodegenerative genetic disorder, diagnosed via DNA testing, that affects approximately 200 children in the United States at any one time. This study was conducted to evaluate whether quantitative data derived by diffusion-weighted MR imaging (DWI) techniques can supplement clinical disability scale information to provide a quantitative estimate of neurodegeneration, as well as disease progression and severity.

Materials and methods: This study prospectively analyzed 32 DWI examinations from 18 patients having confirmed LINCL at various stages of disease. A whole-brain apparent diffusion coefficient (ADC) histogram was fitted with a dual Gaussian function combined with a function designed to model voxels containing a partial volume fraction of brain parenchyma versus CSF. Previously published whole-brain ADC values of age-matched control subjects were compared with those of the LINCL patients. Correlations were tested between the peak ADC of the fitted histogram and patient age, disease severity, and a CNS disability scale adapted for LINCL.

Results: ADC values assigned to brain parenchyma were higher than published ADC values for age-matched control subjects. ADC values between patients and control subjects began to differ at 5 years of age based on 95% confidence intervals. ADC values had a nearly equal correlation with patient age (R2=0.71) and disease duration (R2=0.68), whereas the correlation with the central nervous system disability scale (R2=0.27) was much weaker.

Conclusion: This study indicates that brain ADC values acquired using DWI may be used as an independent measure of disease severity and duration in LINCL.

Fig 1.

A, A diffusion-weighted image (b = 1000 s/mm²) and an image acquired without diffusion weighting (B) show enlarged sulci and dilated ventricles consistent with atrophic changes from a representative patient with LINCL.

Fig 2.

A whole-brain ADC histogram from a representative patient with LINCL shows the dual Gaussian and partial volume functions that were used to fit the whole brain, partial volume, and CSF compartments.

Fig 3.

Voxels associated with specific ranges of ADC values provide visual confirmation that compartments identified as whole brain, partial volume, and CSF correspond with specific regions as shown from a representative section of a patient with LINCL. ADC ranges displayed are described below. A, 1.0 ± 0.2 × 10⁻³ mm²/s. B, 1.5 ± 0.2 × 10⁻³ mm²/s. C, 2.0 ± 0.2 × 10⁻³ mm²/s. D, 2.5 ± 0.2 × 10⁻³ mm²/s. E, 3.0 ± 0.2 × 10⁻³ mm²/s. F, 3.5 ± 0.2 × 10⁻³ mm²/s.

Fig 4.

The whole-brain ADC value is plotted versus age for all of the patients showing an increasing trend over time. Serial studies are connected by lines, and the CNS disability scale is shown in the legend. Previously published whole-brain ADC values from age-matched control subjects are plotted for comparison.