Tang Jingyi, Xing Wu, Wang Dongcui, Qin Yan, Li Junfeng, Zhang Youming, Yang Fangxue, Zhou Gaofeng, Jiang Hong, Liao Weihua
Department of Radiology, Xiangya Hospital of Central South University, Changsha, 410008, China.
Department of Radiology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, 046000, China.
Neuroscience. 2025 Feb 16;567:77-85. doi: 10.1016/j.neuroscience.2024.12.055. Epub 2024 Dec 31.
Widespread white matter (WM) microstructural abnormalities have been reported in patients with spinocerebellar ataxia type 3 (SCA3) using diffusion tensor imaging (DTI), whereas the ability of DTI to detect WM degeneration over short-term period remains insufficiently explored. Additionally, WM dysfunction remains entirely unknown in this disease. This study aims to investigate WM structural and functional alterations in SCA3, and provide promising progression biomarkers for short-term clinical trials. DTI and resting-state functional magnetic resonance imaging data of 52 SCA3 patients and 56 healthy controls (HCs) were collected at baseline. After a mean follow-up of 1 year, MRI scans were performed on a subset of 28 SCA3 patients. Compared with HCs, widespread WM structural and functional abnormalities were observed in patients with SCA3. Between-group differences of both structural and functional MR metrics showed remarkable similarities, with large differences located in pons and corticospinal tracts, involving cerebellar WM, cerebellar and cerebral peduncles, medial lemniscus and bilateral posterior limb of internal capsule (PLIC). The longitudinal analysis further showed decreased ALFF in the right PLIC and increased mean diffusivity in the left inferior cerebellar peduncle and right medial lemniscus over time in SCA3 patients. These findings emphasized that pons and the CST were the most vulnerable WM areas in SCA3, and have the potential to become therapeutic targets of SCA3 for upcoming interventional trials. In addition, both DT metrics and WM ALFF were efficient progression biomarkers for SCA3 even in short-term period.
使用扩散张量成像（DTI）技术，已报道脊髓小脑共济失调3型（SCA3）患者存在广泛的白质（WM）微观结构异常，然而DTI在短期内检测WM退变的能力仍未得到充分探索。此外，该疾病中WM功能障碍仍完全未知。本研究旨在调查SCA3患者的WM结构和功能改变，并为短期临床试验提供有前景的病情进展生物标志物。在基线时收集了52例SCA3患者和56例健康对照（HCs）的DTI和静息态功能磁共振成像数据。平均随访1年后，对28例SCA3患者的一个子集进行了MRI扫描。与HCs相比，SCA3患者中观察到广泛的WM结构和功能异常。结构和功能磁共振指标的组间差异显示出显著的相似性，差异较大的部位位于脑桥和皮质脊髓束，涉及小脑WM、小脑和大脑脚、内侧丘系以及双侧内囊后肢（PLIC）。纵向分析进一步显示，SCA3患者随时间推移，右侧PLIC的低频振幅（ALFF）降低，左侧小脑下脚和右侧内侧丘系的平均扩散率增加。这些发现强调脑桥和皮质脊髓束是SCA3中最易受损的WM区域，并且有可能成为即将进行的干预试验中SCA3的治疗靶点。此外，即使在短期内，DT指标和WM的ALFF都是SCA3有效的病情进展生物标志物。
