Background Metachromatic leukodystrophy (MLD) is a lysosomal enzyme deficiency disorder leading to progressive demyelination and, consecutively, to cognitive and motor decline. Brain magnetic resonance imaging (MRI) can detect affected white matter as T2 hyperintense areas but cannot quantify the gradual microstructural process of demyelination more accurately. Our study aimed to investigate the value of routine MR diffusion tensor imaging in assessing disease progression.

Methods MR diffusion parameters (apparent diffusion coefficient [ADC] and fractional anisotropy [FA]) were in the frontal white matter, central region (CR), and posterior limb of the internal capsule in 111 MR datasets from a natural history study of 83 patients (age: 0.5–39.9 years; 35 late-infantile, 45 juvenile, 3 adult, with clinical diffusion sequences of different scanner manufacturers) as well as 120 controls. Results were correlated with clinical parameters reflecting motor and cognitive function.

Results ADC values increase and FA values decrease depending on disease stage/severity. They show region-specific correlations with clinical parameters of motor and cognitive symptoms, respectively. Higher ADC levels in CR at diagnosis predicted a disease course with more rapid motor deterioration in juvenile MLD patients. In highly organized tissues such as the corticospinal tract, in particular, diffusion MR parameters were highly sensitive to MLD-associated changes and did not correlate with the visual quantification of T2 hyperintensities.

Conclusion Our results show that diffusion MRI can deliver valuable, robust, clinically meaningful, and easily obtainable/accessible/available parameters in the assessment of prognosis and progression of MLD. Therefore, it provides additional quantifiable information to established methods such as T2 hyperintensity.

背景 异染性脑白质营养不良 (MLD) 是一种溶酶体酶缺乏症，导致进行性脱髓鞘，进而导致认知和运动能力下降。脑磁共振成像 (MRI) 可以将受影响的白质检测为 T2 高信号区域，但无法更准确地量化脱髓鞘的渐进微观结构过程。我们的研究旨在探讨常规磁共振扩散张量成像在评估疾病进展中的价值。

方法 MR 扩散参数（表观扩散系数 [ADC] 和分数各向异性 [FA]）位于额叶白质、中央区域 (CR) 和内囊后肢，来自 83 名患者的自然病史研究的 111 个 MR 数据集中（年龄：0.5-39.9 岁；35 名晚期婴儿，45 名青少年，3 名成人，具有不同扫描仪制造商的临床扩散序列）以及 120 名对照。结果与反映运动和认知功能的临床参数相关。

结果 ADC 值增加而 FA 值降低，具体取决于疾病阶段/严重程度。它们分别显示出与运动和认知症状的临床参数的区域特异性相关性。诊断时 CR 中较高的 ADC 水平预示着青少年 MLD 患者的病程会出现更快的运动恶化。特别是在皮质脊髓束等高度组织化的组织中，扩散 MR 参数对 MLD 相关的变化高度敏感，并且与 T2 高信号的视觉量化不相关。

结论 我们的结果表明，在评估 MLD 的预后和进展时，扩散 MRI 可以提供有价值、稳健、有临床意义且易于获得/可获取/可用的参数。因此，它为 T2 高信号等既定方法提供了额外的可量化信息。