BackgroundThe dentate nuclei of the cerebellum are key sites of neuropathology in Friedreich ataxia (FRDA). Reduced dentate nucleus volume and increased mean magnetic susceptibility, a proxy of iron concentration, have been reported by magnetic resonance imaging studies in people with FRDA. Here, we investigate whether these changes are regionally heterogeneous.MethodsQuantitative susceptibility mapping data were acquired from 49 people with FRDA and 46 healthy controls. The dentate nuclei were manually segmented and analyzed using three dimensional vertex‐based shape modeling and voxel‐based assessments to identify regional changes in morphometry and susceptibility, respectively.ResultsIndividuals with FRDA, relative to healthy controls, showed significant bilateral surface contraction most strongly at the rostral and caudal boundaries of the dentate nuclei. The magnitude of this surface contraction correlated with disease duration, and to a lesser extent, ataxia severity. Significantly greater susceptibility was also evident in the FRDA cohort relative to controls, but was instead localized to bilateral dorsomedial areas, and also correlated with disease duration and ataxia severity.ConclusionsChanges in the structure of the dentate nuclei in FRDA are not spatially uniform. Atrophy is greatest in areas with high gray matter density, whereas increases in susceptibility—reflecting iron concentration, demyelination, and/or gliosis—predominate in the medial white matter. These findings converge with established histological reports and indicate that regional measures of dentate nucleus substructure are more sensitive measures of disease expression than full‐structure averages. Biomarker development and therapeutic strategies that directly target the dentate nuclei, such as gene therapies, may be optimized by targeting these areas of maximal pathology. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

中文翻译：

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Friedreich 共济失调齿状核形状和磁化率的局部变化

背景小脑齿状核是弗里德赖希共济失调 (FRDA) 神经病理学的关键部位。 FRDA 患者的磁共振成像研究报告称，齿状核体积减少，平均磁化率（铁浓度的代表）增加。在这里，我们调查这些变化是否具有区域异质性。方法从 49 名 FRDA 患者和 46 名健康对照者中获取定量敏感性图谱数据。使用基于三维顶点的形状建模和基于体素的评估对齿状核进行手动分割和分析，以分别识别形态测量和敏感性的区域变化。结果相对于健康对照，患有 FRDA 的个体在齿状核的头侧和尾侧边界。这种表面收缩的幅度与疾病持续时间相关，并且在较小程度上与共济失调的严重程度相关。与对照组相比，FRDA 队列中的易感性也明显更高，但局限于双侧背内侧区域，并且还与疾病持续时间和共济失调严重程度相关。 结论 FRDA 中齿状核结构的变化在空间上并不均匀。灰质密度高的区域萎缩最严重，而易感性增加（反映铁浓度、脱髓鞘和/或神经胶质增生）主要发生在内侧白质。这些发现与已建立的组织学报告一致，表明齿状核亚结构的区域测量是比全结构平均值更敏感的疾病表达测量。直接针对齿状核的生物标志物开发和治疗策略（例如基因疗法）可以通过针对这些最大病理学区域来优化。 © 2024 作者。运动障碍由 Wiley periodicals LLC 代表国际帕金森和运动障碍协会出版。