Stellingwerff Menno D, Al-Saady Murtadha L, Chan Kwok-Shing, Dvorak Adam, Marques José P, Kolind Shannon, Schoenmakers Daphne H, van Voorst Romy, Roosendaal Stefan D, Barkhof Frederik, Wolf Nicole I, Berkhof Johannes, Pouwels Petra J W, van der Knaap Marjo S
Amsterdam Leukodystrophy Center, Department of Child Neurology, Emma Children's Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Cellular & Molecular Mechanisms, Vrije Universiteit, Amsterdam, The Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Eur Radiol. 2025 Apr;35(4):1845-1857. doi: 10.1007/s00330-024-11089-5. Epub 2024 Sep 25.
The leukodystrophy "vanishing white matter" (VWM) and "metachromatic leukodystrophy" (MLD) affect the brain's white matter, but have very different underlying pathology. We aim to determine whether quantitative MRI reflects known neuropathological differences and correlates with clinical scores in these leukodystrophies.
VWM and MLD patients and controls were prospectively included between 2020 and 2023. Clinical scores were recorded. MRI at 3 T included multi-compartment relaxometry diffusion-informed myelin water imaging (MCR-DIMWI) and multi-echo T2-relaxation imaging with compressed sensing (METRICS) to determine myelin water fractions (MWF). Multi-shell diffusion-weighted data were used for diffusion tensor imaging measures and neurite orientation dispersion and density imaging (NODDI) analysis, which estimates neurite density index, orientation dispersion index, and free water fraction. As quantitative MRI measures are age-dependent, ratios between actual and age-expected MRI measures were calculated. We performed the multilevel analysis with subsequent post-hoc and correlation tests to assess differences between groups and clinico-radiological correlations.
Sixteen control (age range: 2.3-61.3 years, 8 male), 37 VWM (2.4-56.5 years, 20 male), and 14 MLD (2.2-41.7 years, 6 male) subjects were included. Neurite density index and MWF were lower in patients than in controls (p < 0.001). Free water fraction was highest in VWM (p = 0.01), but similar to controls in MLD (p = 0.99). Changes in diffusion tensor imaging measures relative to controls were generally more pronounced in VWM than in MLD. In both patient groups, MCR-DIMWI MWF correlated strongest with clinical measures.
Quantitative MRI correlates to clinical measures and yields differential profiles in VWM and MLD, in line with differences in neuropathology.
Question Can quantitative MRI reflect known neuropathological differences and correlate with clinical scores for these leukodystrophies? Finding Quantitative MRI measures, e.g., MWF, neurite density index, and free water fraction differ between leukodystrophies and controls, in correspondence to known histological differences. Clinical relevance MRI techniques producing quantitative, biologically-specific, measures regarding the health of myelin and axons deliver more comprehensive information regarding pathological changes in leukodystrophies than current approaches, and are thus viable tools for monitoring patients and providing clinical trial outcome measures.
脑白质营养不良“消失性白质病”（VWM）和“异染性脑白质营养不良”（MLD）会影响大脑白质，但潜在病理机制截然不同。我们旨在确定定量MRI是否能反映已知的神经病理学差异，并与这些脑白质营养不良的临床评分相关。
前瞻性纳入2020年至2023年间的VWM和MLD患者及对照组。记录临床评分。3T MRI包括多成分弛豫测量扩散知情髓鞘水成像（MCR-DIMWI）和压缩感知多回波T2弛豫成像（METRICS）以确定髓鞘水分数（MWF）。多壳扩散加权数据用于扩散张量成像测量和神经突方向离散度与密度成像（NODDI）分析，后者可估计神经突密度指数、方向离散度指数和自由水分数。由于定量MRI测量值与年龄相关，因此计算实际测量值与年龄预期测量值之间的比率。我们进行了多水平分析，随后进行事后检验和相关性检验，以评估组间差异和临床-放射学相关性。
纳入了16名对照组（年龄范围：2.3 - 61.3岁，8名男性）、37名VWM患者（2.4 - 56.5岁，20名男性）和14名MLD患者（2.2 - 41.7岁，6名男性）。患者的神经突密度指数和MWF低于对照组（p < 0.001）。自由水分数在VWM中最高（p = 0.01），但在MLD中与对照组相似（p = 0.99）。相对于对照组，扩散张量成像测量值的变化在VWM中通常比在MLD中更明显。在两个患者组中，MCR-DIMWI MWF与临床指标的相关性最强。
定量MRI与临床指标相关，并在VWM和MLD中产生不同的特征，与神经病理学差异一致。
问题 定量MRI能否反映已知的神经病理学差异，并与这些脑白质营养不良的临床评分相关？发现 定量MRI测量值，如MWF、神经突密度指数和自由水分数，在脑白质营养不良患者和对照组之间存在差异，与已知的组织学差异相符。临床意义 与当前方法相比，能产生关于髓鞘和轴突健康的定量、生物学特异性测量值的MRI技术，可提供关于脑白质营养不良病理变化的更全面信息，因此是监测患者和提供临床试验结果测量值的可行工具。
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