Hypoperfusion predicts lesion progression in cerebral X-linked adrenoleukodystrophy

Area of Science:

• Neuroimaging
• Neurology
• Medical Physics

Background:

• X-linked adrenoleukodystrophy (X-ALD) affects the adrenal glands, testes, and white matter of the central nervous system.
• While diffusion and spectroscopy MRI are established for X-ALD, perfusion imaging data are lacking.
• Inflammation in X-ALD is known to affect microcirculation, suggesting perfusion changes may precede lesion development.

Purpose of the Study:

• To investigate the hypothesis that altered local perfusion is an early indicator of lesion development in X-linked adrenoleukodystrophy.
• To evaluate the utility of magnetic resonance (MR) perfusion imaging in characterizing X-ALD lesions.
• To compare perfusion changes in different X-ALD phenotypes and disease progression stages.

Main Methods:

• Utilized normalized dynamic susceptibility contrast (DSC) MR perfusion imaging to assess cerebral blood volume (CBV).
• Co-registered DSC-CBV maps with Fluid Attenuated Inversion Recovery (FLAIR) and post-contrast T1-weighted images.
• Analyzed CBV values using FDA-approved NordicICE software in 20 X-ALD patients and 7 controls.

Main Results:

• Patients with cerebral X-ALD showed an 80% average decrease in normalized CBV at the lesion core (P < 0.0001).
• Progressive lesions exhibited a 60% average decrease in perilesional normalized CBV (children P < 0.001, adults P < 0.05).
• Decreased brain MR perfusion was observed before contrast enhancement, indicating blood-brain barrier leakage, and preceded lesion progression.

Conclusions:

• Reduced brain MR perfusion is an early sign of lesion progression in X-linked adrenoleukodystrophy.
• Perfusion deficits precede blood-brain barrier breakdown, offering a potential early diagnostic marker.
• Asymptomatic, adrenomyeloneuropathy, and female heterozygote X-ALD patients showed no significant changes in cerebral perfusion.