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Diffusion Tensor Imaging in Boys With Adrenoleukodystrophy: Identification of Cerebral Disease and Association With
Elizabeth I Pierpont1, René Labounek1, Ashish Gupta1
1From the Departments of Pediatrics (E.I.P., R.L., A.G., T.L., P.J.O., W.B.D., M.B., A.P., I.N.), Neurology (A.M.), Psychiatry & Behavioral Sciences (J.R.W., B.A.M.), and Radiology (D.N.), University of Minnesota Medical School, Minneapolis; Biostatistical Design and Analysis Center (R.S.), Clinical and Translational Science Institute, University of Minnesota, Minneapolis; and Independent Neuroradiologist-Consultant (D.L.), Minneapolis, MN.
Insights
Diffusion tensor imaging (DTI) detects early signs of childhood cerebral adrenoleukodystrophy (C-ALD) and correlates with neurocognitive outcomes after treatment. DTI metrics quantify C-ALD severity, aiding timely intervention to prevent brain injury.
Area of Science:
- Neuroimaging
- Neurology
- Pediatric Medicine
Background:
- Childhood cerebral adrenoleukodystrophy (C-ALD) is a severe inflammatory demyelinating disease requiring early intervention to prevent neurocognitive decline.
- Current detection relies on anatomical MRI, potentially missing early disease stages.
- Hematopoietic cell therapy (HCT) is a primary treatment for C-ALD.
Purpose of the Study:
- To evaluate the sensitivity of diffusion tensor imaging (DTI) in detecting C-ALD lesions and assessing their severity.
- To investigate the association between DTI metrics and neurocognitive outcomes post-HCT.
- To determine if DTI can identify C-ALD at early stages.
Main Methods:
- Retrospective analysis of anatomical MRI, DTI, and neurocognitive data from boys with C-ALD undergoing HCT.
- Comparison of DTI metrics (FA, AD, RD, MD) in regions of interest (corpus callosum, corticospinal tract, white matter) between C-ALD patients and a control group (ALD with no lesions).
- Statistical analysis (ANCOVA) to compare baseline and longitudinal DTI differences, accounting for age, Loes score, and lesion location.
Main Results:
- Patients with early C-ALD lesions showed significantly lower fractional anisotropy (FA) and higher diffusivities (AD, RD, MD) in key white matter tracts compared to controls.
- Longitudinal DTI metrics, particularly in the corpus callosum splenium, demonstrated high sensitivity and specificity for differentiating early C-ALD from no lesion ALD.
- Baseline DTI metrics and Loes scores correlated significantly with post-HCT neurocognitive functions, including processing speed and visual-motor integration.
Conclusions:
- Diffusion tensor imaging is sensitive to the presence and severity of C-ALD lesions.
- DTI metrics correlate with clinical neurocognitive effects and can quantify C-ALD even in early stages.
- DTI shows promise as a valuable tool for early C-ALD detection and monitoring treatment response.
Background And Objectives:
Childhood cerebral adrenoleukodystrophy (C-ALD) is a severe inflammatory demyelinating disease that must be treated at an early stage to prevent permanent brain injury and neurocognitive decline. In standard clinical practice, C-ALD lesions are detected and characterized by a neuroradiologist reviewing anatomical MRI scans. We aimed to assess whether diffusion tensor imaging (DTI) is sensitive to the presence and severity of C-ALD lesions and to investigate associations with neurocognitive outcomes after hematopoietic cell therapy (HCT).
Methods:
In this retrospective cohort study, we analyzed high-resolution anatomical MRI, DTI, and neurocognitive assessments from boys with C-ALD undergoing HCT at the University of Minnesota between 2011 and 2021. Longitudinal DTI data were compared with an age-matched group of boys with ALD and no lesion (NL-ALD). DTI metrics were obtained for atlas-based regions of interest (ROIs) within 3 subdivisions of the corpus callosum (CC), corticospinal tract (CST), and total white matter (WM). Between-group baseline and slope differences in fractional anisotropy (FA) and axial (AD), radial (RD), and mean (MD) diffusivities were compared using analysis of covariance accounting for age, MRI severity (Loes score), and lesion location.
Results:
Among patients with NL-ALD (n = 14), stable or increasing FA, stable AD, and stable or decreasing RD and MD were generally observed during the 1-year study period across all ROIs. In comparison, patients with mild posterior lesions (Loes 1-2; n = 13) demonstrated lower baseline FA in the CC splenium (C-ALD 0.50 ± 0.08 vs NL-ALD 0.58 ± 0.04; pBH = 0.022 adjusted Benjamini-Hochberg p-value), lower baseline AD across ROIs (e.g., C-ALD 1.34 ± 0.03 ×10-9 m2/s in total WM vs NL-ALD 1.38 ± 0.04 ×10-9 m2/s; pBH = 0.005), lower baseline RD in CC body and CST, and lower baseline MD across ROIs except CC splenium. Longitudinal slopes in CC splenium showed high sensitivity and specificity in differentiating early C-ALD from NL-ALD. Among all patients with C-ALD (n = 38), baseline Loes scores and DTI metrics were associated with post-HCT neurocognitive functions, including processing speed (e.g., FA WM Spearman correlation coefficient R = 0.64) and visual-motor integration (e.g., FA WM R = 0.71).
Discussion:
DTI was sensitive to lesion presence and severity as well as clinical neurocognitive effects of C-ALD. DTI metrics quantify C-ALD even at an early stage.
