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Review
. 2023:38:103427.
doi: 10.1016/j.nicl.2023.103427. Epub 2023 May 3.

Quantitative MRI in leukodystrophies

Menno D Stellingwerff  1 , Petra J W Pouwels  2 , Stefan D Roosendaal  3 , Frederik Barkhof  4 , Marjo S van der Knaap  5
Affiliations
Review

Quantitative MRI in leukodystrophies

Menno D Stellingwerff et al. Neuroimage Clin. 2023.

Abstract

Leukodystrophies constitute a large and heterogeneous group of genetic diseases primarily affecting the white matter of the central nervous system. Different disorders target different white matter structural components. Leukodystrophies are most often progressive and fatal. In recent years, novel therapies are emerging and for an increasing number of leukodystrophies trials are being developed. Objective and quantitative metrics are needed to serve as outcome measures in trials. Quantitative MRI yields information on microstructural properties, such as myelin or axonal content and condition, and on the chemical composition of white matter, in a noninvasive fashion. By providing information on white matter microstructural involvement, quantitative MRI may contribute to the evaluation and monitoring of leukodystrophies. Many distinct MR techniques are available at different stages of development. While some are already clinically applicable, others are less far developed and have only or mainly been applied in healthy subjects. In this review, we explore the background, current status, potential and challenges of available quantitative MR techniques in the context of leukodystrophies.

Keywords: Leukodystrophies; Myelin imaging; Quantitative MRI; White matter disorders.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Heterogeneous neuropathology of leukodystrophies. A) Metachromatic leukodystrophy (MLD) is characterized by loss of myelin (Klüver-periodic acid-Schiff (PAS), blue) and accumulation of myelin debris in macrophages (pink). Dense astrogliosis is present (inset in A, GFAP staining). B) Megalencephalic Leukodystrophy with subcortical Cysts is characterized by white matter vacuolization (haematoxylin and eosin (HE)) without lack of myelin (inset in B, toluidine blue). C) Vanishing White Matter is characterized by loss of virtually all white matter components (HE) and a profound lack of astrogliosis (inset in C, GFAP staining). Magnification of all staining is 400x.\
Fig. 2
Fig. 2
A) T2-weighted FLAIR and B) ultrashort TE subtraction images in a 45-year-old woman with MS, indicating a lower signal intensity in the UTE image in lesions that appear hyperintense on FLAIR. Adapted with permission from Ma et al., 2020.
Fig. 3
Fig. 3
A) Normal magnetization transfer (MT) findings in an 11-year-old healthy control. B) Decreased MT ratios are visible in the cerebral white matter of a 13-year-old subject with the leukodystrophy Hypomyelination and Atrophy of Basal ganglia and Cerebellum, while the T1-weighted image still shows a relatively normal hyperintense T1-signal. Adapted with permission from Dreha-Kulaczewski et al., 2012.
Fig. 4
Fig. 4
Myelin water fraction maps from a healthy subject with GRASE (A) and mcDESPOT (B). The two maps are shown with the same color bar (with values ranging from 0 to 0.3). The maps show higher MWF in white matter than in gray matter, but values differ between both techniques. Adapted with permission from Zhang et al., 2015.
Fig. 5
Fig. 5
A) Postmortem myelin water map and corresponding Luxol fast blue-staining of the temporal lobe region of a multiple sclerosis (MS) patient. B) T2-weighted image and corresponding multi-echo spin echo (MESE) sequence derived myelin water fraction-map of an MS patient, showing a reduced myelin water fraction in the MS lesions (arrows). A) Adapted with permission from Laule et al., 2008; B)
Fig. 6
Fig. 6
T2-weighted FLAIR and corresponding SyMRI myelin map in 4 subjects. A) A 56-year-old healthy control. B) A 53-year-old patient with primary progressive multiple sclerosis (MS). C) A 39-year-old patient with relapsing–remitting MS. D) A 40-year-old patient with secondary progressive MS. The myelin map shows the lowest values in the patient with secondary progressive MS, and the highest values in the healthy control. Adapted with permission from Ouellette et al., 2020.
Fig. 7
Fig. 7
Healthy control (upper row) and a patient with metachromatic leukodystrophy (MLD, lower row) with normal T2-weighted signal intensity in cerebral white matter, which was T2-hyperintense in previously obtained MR scans. Besides DTI-parameters such as MD and FA, NODDI can model the neurite density index (NDI) and the free water fraction. The neurite density is clearly reduced in the normal looking white matter in the MLD patient, confirming pseudo-normalization.
Fig. 8
Fig. 8
MR spectra of two patients with metachromatic leukodystrophy (MLD). A) Juvenile MLD with a poor outcome. N-acetylaspartate (NAA) concentration is highly decreased, while lactate (Lac) is increased. B) Juvenile MLD with good outcome. NAA concentration is normal and no Lac is detected.
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