Hypoperfusion predicts lesion progression in cerebral X-linked adrenoleukodystrophy

Abstract

Magnetic resonance imaging sequences such as diffusion and spectroscopy have been well studied in X-linked adrenoleukodystrophy, but no data exist on magnetic resonance perfusion imaging. Since inflammation is known to modulate the microcirculation, we investigated the hypothesis that changes in the local perfusion might be one of the earliest signs of lesion development. Twenty patients with different phenotypes of adrenoleukodystrophy and seven age-matched controls were evaluated between 2006 and 2011. Fluid attenuated inversion recovery, post-contrast T(1)-weighted and normalized dynamic susceptibility contrast magnetic resonance perfusion cerebral blood volume maps were co-registered, segmented when cerebral lesion was present, and normalized cerebral blood volume values were analysed using a Food and Drug Association approved magnetic resonance perfusion software (NordicICE). Clinical and imaging data were reviewed to determine phenotype and status of progression. All eight patients with cerebral adrenoleukodystrophy had an average 80% decrease in normalized cerebral blood volume at the core of the lesion (P < 0.0001). Beyond the leading edge of contrast enhancement cerebral perfusion varied, patients with progressive lesions showed an average 60% decrease in normalized cerebral blood volume (adults P < 0.05; children P < 0.001), while one child with arrested progression normalized cerebral blood volume in this region. In six of seven patients with cerebral adrenoleukodystrophy lesions and follow-up imaging (2-24 month interval period), we found progression of contrast enhancement into the formerly hypoperfused perilesional zone. Asymptomatic, adrenomyeloneuropathy and female heterozygote patients had no significant changes in cerebral perfusion. Our data indicate that decreased brain magnetic resonance perfusion precedes leakage of the blood-brain barrier as demonstrated by contrast enhancement in cerebral adrenoleukodystrophy and is an early sign of lesion progression.

Figure 1

Nine-year-old male patient with childhood cerebral adrenoleukodystrophy (ALD). Top: FLAIR, post-contrast axial T₁-weighted (T1-POST), and normalized cerebral blood volume (nCBV) map. Bottom: Co-registered images with regions of interest (ROIs). Five different zones of involvement are distinguished in the white matter (Zones A–E; see main text). In patients with non-cerebral disease (adrenomyeloneuropathy, female heterozygotes, asymptomatic males and controls) representative regions of normal-appearing white matter were assessed.

Figure 2

Normalized cerebral blood volume (nCBV) measured by dynamic susceptibility contrast magnetic resonance perfusion imaging was significantly decreased in zones A, C and D in patients with cerebral adrenoleukodystrophy (CALD) but not in patients without lesions (non-cerebral). In the core of the lesion (Zone A), normalized cerebral blood volume was 80% lower than that in corresponding white matter of control brain. Beyond the region of contrast enhancement (Zones C and D), normalized cerebral blood volume was up to 60% lower in patients with cerebral adrenoleukodystrophy compared with controls. ACALD = adult cerebral adrenoleukodystrophy; CCALD = childhood cerebral adrenoleukodystrophy; HSCT = haematopoetic stem cell transplantation; ROIs = regions of interest.

Figure 3

Decreased brain magnetic resonance perfusion in cerebral adrenoleukodystrophy precedes lesion progression. Top: T₂, T₁ post-contrast weighted and T₁-post contrast images co-registered with normalized cerebral blood volume images of a 9-year-old child with progressive cerebral adrenoleukodystrophy shows decreased magnetic resonance perfusion beyond the contrast enhancing region (empty arrows; Zone D). Follow-up T₁-post contrast weighted imaging after 12 months shows lesion extension and advancement of contrast material (solid arrows) into prior hypoperfused region. Bottom: T₂, T₁ post-contrast weighted and T₁-post contrast images co-registered with normalized cerebral blood volume images of a 12-year-old child with cerebral adrenoleukodystrophy (CCALD) shows normal normalized cerebral blood volume beyond the contrast enhancing region (empty arrows; Zone D) 9 months after the engraftment of haematopoietic stem cell transplantation (HSCT). No lesion progression was observed up to 14 months post-transplant. Contrast material (solid arrows) has not advanced.