14800-DvRappard

125 Diffusion tensor imaging in metachromatic leukodystrophy 8 INTRODUCTION Metachromatic leukodystrophy (MLD, OMIM 250100) is an autosomal recessive lysosomal disorder caused by mutations in ARSA . This results in deficiency of the enzyme arylsulfatase A (ASA), essential for sulfatide metabolism. 1 Sulfatides are major myelin lipids; their accumulation, mainly in membranes, leads to demyelination and subsequently storage in macrophages that cannot digest them. 1 MLD is a devastating disease: without treatment, eventually all acquired skills are lost and patients die. MLD has three clinical subtypes, based on age of onset. The late-infantile form starts before 30 months, usually presenting with motor deterioration. The juvenile form presents with a combination of motor and cognitive decline before 16 years. The adult form begins with cognitive decline and psychiatric symptoms thereafter. 2 When performed early, hematopoietic cell therapy (HCT) has promising results, especially for juvenile and adult patients. 3,4 Brain magnetic resonance imaging (MRI) in MLD is characterized by bilateral symmetric T2 signal hyperintensities, starting in the corpus callosum and subsequently involving the periventricular white matter (WM), followed by projection fibers and cerebellar WM.(5) Thalamic volume and signal intensity on T2-weighted images in the thalamus are decreased already at diagnosis. 6,7 Typical for MLD are stripes of low signal intensity throughout the hyperintense signal on T2-weighted images in the cerebral WM, related both to the accumulation of macrophages bursting with undigested lipids and to better preserved perivascular myelin. 8 Brain diffusion tensor imaging (DTI) is based on the motion of water molecules, which is more restricted perpendicular to than along WM fibers, a feature termed diffusion anisotropy. 9 Magnitude and direction of diffusivity are determined by molecules, membranes and microtubules, and provide information about tissue composition and microstructure and its architectural organization. 10,11 The tensor model is a relatively simple model using diffusion weighted images (DWI) obtainedwith one b-value. It results in axial diffusivity (AD), radial diffusivity (RD) and the derived fractional anisotropy (FA) and mean diffusivity (MD).(11) Often, RD is thought to be correlated to myelin degradation and AD to axonal degeneration or inflammation and gliosis, 12-17 but it is difficult to unequivocally associate the interpretation of diffusivity variations with specific biophysical changes. 18