Department of Advanced Biomedical Sciences, University of Naples "Federico II", Naples, Italy.
Department of Computer Science, Diffusion Imaging and Connectivity Estimation (DICE) Lab, University of Verona, Verona, Italy.
Ann Clin Transl Neurol. 2024 Jul;11(7):1691-1702. doi: 10.1002/acn3.52048. Epub 2024 Jul 1.
The dentato-thalamo-cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach.
MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross-sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison.
Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted.
Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex.
齿状核-丘脑-皮质束（DTT）是小脑的主要传出通路。DTT 的退化是弗里德里希共济失调（FRDA）的核心特征。然而，DTT 的破坏是否具有空间特异性，即某些节段比其他节段受影响更大，目前仍不清楚。本研究旨在使用基于轮廓的扩散 MRI（dMRI）方法研究 FRDA 中 DTT 的微观结构完整性。
本横断面多中心研究纳入了 45 名 FRDA 患者（平均年龄：33.2±13.2，男/女：26/19）和 37 名健康对照者（平均年龄：36.5±12.7，男/女：18/19）的 MRI 数据。通过首先使用轨迹追踪来定义 DTT，即将齿状核连接到对侧运动皮质的白质通路，从而在 dMRI 数据上进行轮廓分析。将束分为 100 个节段，并比较组间每个节段的微观结构完整性（各向异性分数、平均弥散度和径向弥散度）的 dMRI 指标。该过程在弓状束上进行复制以作比较。
在所有扩散指标中，FRDA 患者的 DTT 中连接齿状核和丘脑的区域比丘脑到皮质的下游脑区更受影响。弓状束受影响最小。
本研究进一步扩展了 FRDA 中大脑受累的现有知识，表明 DTT 内的微观结构异常主要集中在束的早期节段（即上小脑脚）。这些发现与 DTT 发生顺行性退化的假说一致，即退化始于齿状核，向初级运动皮质发展。
