Quantitative brain MRI morphology in severe and attenuated forms of mucopolysaccharidosis type I

Abstract

Objective: To assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition.

Methods: Brain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4-25 years, enrolled under the study protocol NCT01870375, were compared to 98 healthy controls.

Results: Cortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC. Thicker cortex, lower white matter and corpus callosum volumes were already present at the youngest MPS I participants aged 4-5 years. Age-related differences were observed in both MPS I groups, but most markedly in MPS IH, particularly in cortical gray matter metrics. IQ scores were inversely associated with ventricular volume in both MPS I groups and were positively associated with cortical thickness only in MPS IA.

Conclusions: Quantitatively-derived MRI measures distinguished MPS I participants from HC as well as severe from attenuated forms. Age-related neurodevelopmental trajectories in both MPS I forms differed from HC. The extent to which brain structure is altered by disease, potentially spared by treatment, and how it relates to neurocognitive dysfunction needs further exploration.

Keywords: Brain MRI; Cortex; Hurler Scheie syndrome; Mucopolysaccharidosis; Quantitative brain volumetry; Ventricle.

Copyright © 2022 Elsevier Inc. All rights reserved.

Figures

Figure 1

Corrections of automated brain MRI segmentation in MPS I participants. Coronal T1-weighted images. Pial surface – red line, cerebral white matter surface – yellow line. A. White and gray matter segmentation of the left temporal lobe with the placement of control points (green cross) in the under-segmented white matter (arrows). Edited scans before and after an iteration of automated segmentation. Relatively small parts of mesiotemporal structures may remain unsegmented (dashed arrow) due to the low gray/white matter contrast. B. Brain mislabeling at the level of lateral ventricles (purple label) due to the prominent ventricular enlargement (arrows). Scans are shown before and after an iteration of automated segmentation with -bigventricles flag. Color-coded labels overlaid on T1-weighted image correspond to specific brain regions.

Figure 2

Brain MRI measure vs. age for MPS IA and MPS IH participants and healthy controls. Age in years on the x-axis, brain MRI measure on the y-axis.HC healthy control, MPS IA attenuated form of mucopolysaccharidosis type I, MPS IH severe form of mucopolysaccharidosis type I, CSF cerebrospinal fluid, corresponds to total ventricular volume.

Figure 3

Cortical thickness and ventricular volume (CSF) vs. IQ for MPS IA and MPS IH participants and healthy controls. Brain measure on the x-axis, IQ score on the y-axis. HChealthy control, MPS IA attenuated form of mucopolysaccharidosis type I, MPS IH severe form of mucopolysaccharidosis type I,CSF cerebrospinal fluid, corresponds to total ventricular volume.