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• W1427837033 abstract "OBJECTIVE AND BACKGROUND: Cerebral X-linked adrenoleukodystrophy is a neurodegenerative disorder that results from mutations in the ABCD1 gene and manifests as progressive inflammatory demyelination, neurological dysfunction, and death within few years. We set out to assess changes in perfusion and permeability of white matter microvessels in relation to concurrent tissue oxygen extraction.METHODS: Six patients with adrenoleukodystrophy were evaluated between 2006 and 2014. Based on lesion segmentation of white matter (WM) from conventional imaging, capillary transit time heterogeneity (CTH), maximum oxygen extraction fraction (OEFmax), permeability constant (K2), mean transit time (MTT), cerebral blood flow (CBF) and cerebral blood volume (CBV) were estimated from dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Leakage corrected perfusion maps were obtained using flow-diffusion equation algorithms as described by Ostergaard. Regions of interest were drawn in co-registered maps (A: non-enhancing FLAIR hyperintense core, B: T1-post contrast enhancing rim, and C: FLAIR hyperintense perilesional WM).RESULTS: In patients with cerebral ALD we found an increase in capillary contrast permeability at the core of the demyelinating lesion (Zone A) and the contrast enhancing rim (Zone B). The CTH and MTT were elevated in Zone A consistent with heterogeneous oxygen extraction throughout the capillary bed and likely blood pooling. Moreover, OEFmax was elevated in all areas of FLAIR hyperintensity. As previously published, we found CBV to be markedly decreased within zones A and C and relatively preserved in zone B. In heterozygote and adrenomyeloneuropathy patients no abnormalities were seen within different regions of the WM.CONCLUSION: Zonal abnormalities of brain MR microvascular perfusion were found in patients with cerebral ALD but not AMN or heterozygote. Our analysis provides the first description of abnormal vascular permeability beyond areas of T1-postcontrast enhancement and presents a tool to assess the microvasculature of WM during demyelination. Disclosure: Dr. Musolino has nothing to disclose. Dr. Lauer has nothing to disclose. Dr. Bo Hansen has nothing to disclose. Dr. Kalpathy-Cramer has nothing to disclose. Dr. Mouridsen has nothing to disclose. Dr. Rosen has received personal compensation for activities with Novartis. Dr. Eichler has received personal compensation for activities with Retrophin, Inc." @default.
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• W1427837033 date "2015-04-06" @default.
• W1427837033 modified "2023-10-18" @default.
• W1427837033 title "Oxygen Extraction Fraction and Microvascular Permeability in X-linked Adrenoleukodystrophy (S52.006)" @default.
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