Myelin-water imaging and multi-shell diffusion-weighted imaging in adults with adrenoleukodystrophy

Area of Science:

• Neuroimaging
• Neurology
• Biomedical Engineering

Background:

• X-linked adrenoleukodystrophy (ALD) pathophysiology remains unclear.
• Quantitative MRI (qMRI) techniques like MWI and DWI offer non-invasive insights into brain microstructural changes.
• ALD affects white matter, with cerebral ALD (cALD) being a severe form.

Purpose of the Study:

• To investigate white matter microstructural abnormalities in cALD lesions and normal-appearing white matter (NAWM) using advanced qMRI.
• To compare qMRI measures between ALD patients (with and without cALD) and healthy controls.
• To assess the potential of qMRI for clinical applications in ALD.

Main Methods:

• Adult participants underwent 3T MRI scans.
• Diffusion tensor imaging (DTI) measured fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD).
• Neurite orientation dispersion and density imaging (NODDI) determined the neurite density index (NDI).
• Myelin water fractions (MWF) were assessed using MCR-DIMWI and METRICS techniques.
• Measures were analyzed in 10 regions of interest (ROIs) in 81 ALD participants (17 with cALD) and 21 controls.

Main Results:

• Lesions in cALD patients showed significantly lower FA, NDI, MWF_METRICS, and MWF_MCR-DIMWI compared to controls.
• NAWM in male ALD patients differed from controls in FA, NDI, and MWF_METRICS, but not in females.
• FA and NDI demonstrated the largest effect sizes in males.
• NAWM showed increased RD with largely unaffected AD.
• Some NAWM regions differed between males with and without cALD.

Conclusions:

• The NAWM in males with ALD exhibits microstructural abnormalities.
• ALD pathophysiology impacts myelin and myelinated axons.
• Advanced qMRI techniques show promise for clinical use in ALD diagnosis and monitoring.