T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodyst
- PDF / 1,228,612 Bytes
- 12 Pages / 612.419 x 808.052 pts Page_size
- 50 Downloads / 160 Views
ORIGINAL ARTICLE
T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodystrophy Pascal Martin1 · Gisela E. Hagberg2,3 · Thomas Schultz4 · Klaus Harzer5 · Uwe Klose6 · Benjamin Bender6 · Thomas Nägele6 · Klaus Scheffler2,3 · Ingeborg Krägeloh-Mann5 · Samuel Groeschel5 Received: 27 August 2020 / Accepted: 27 October 2020 © The Author(s) 2020
Abstract Purpose T2-weighted signal hyperintensities in white matter (WM) are a diagnostic finding in brain magnetic resonance imaging (MRI) of patients with metachromatic leukodystrophy (MLD). In our systematic investigation of the evolution of T2-hyperintensities in patients with the late-infantile form, we describe and characterize T2-pseudonormalization in the advanced stage of the natural disease course. Methods The volume of T2-hyperintensities was quantified in 34 MRIs of 27 children with late-infantile MLD (median age 2.25 years, range 0.5–5.2 years). In three children with the most advanced clinical course (age >4 years) and for whom the T2-pseudonormalization was the most pronounced, WM microstructure was investigated using a multimodal MRI protocol, including diffusion-weighted imaging, MR spectroscopy (MRS), myelin water fraction (MWF), magnetization transfer ratio (MTR), T1-mapping and quantitative susceptibility mapping. Results T2-hyperintensities in cerebral WM returned to normal in large areas of 3 patients in the advanced disease stage. Multimodal assessment of WM microstructure in areas with T2-pseudonormalization revealed highly decreased values for NAA, neurite density, isotropic water, mean and radial kurtosis, MWF and MTR, as well as increased radial diffusivity. Conclusion In late-infantile MLD patients, we found T2-pseudonormalization in WM tissue with highly abnormal microstructure characterizing the most advanced disease stage. Pathological hallmarks might be a loss of myelin, but also neuronal loss as well as increased tissue density due to gliosis and accumulated storage material. These results suggest that a multimodal MRI protocol using more specific microstructural parameters than T2-weighted sequences should be used when evaluating the effect of treatment trials in MLD.
Keywords NODDI · Myelin water imaging · Diffusion kurtosis imaging · Magnetization transfer ratio
Abbreviations AD Axial diffusion AK Axial kurtosis Cho/Cr Quotient of choline/creatine peak CS Centrum semiovale DTI Diffusion tensor imaging Consent to participate The authors gave consent to participate in this manuscript.
DWI FA ICVF ISO MD
2
High Field Magnetic Resonance, Max-Planck Institute for Biological Cybernetics, Tübingen, Germany
3
Biomedical Magnetic Resonance, University Hospital, Tübingen, Germany
4
B-IT and Institute of Computer Science, University of Bonn, Bonn, Germany
5
Department of Neuropediatrics, University Children’s Hospital, Tübingen, Germany
6
Department of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Tübingen, Germany
Consent for publication The auth
Data Loading...
