David J. Arpin, S. H. Subramony, the READISCA Consortium, David E. Vaillancourt, Tetsuo Ashizawa, Alexandra Durr, Thomas Mareci, Thomas Klockgether, Jennifer Faber, Henry L. Paulson, Gülin Öz, Matthew R. Burns
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This study aimed to identify white matter differences in the brains of preataxic and early-stage SCA1 and SCA3 mutation carriers using diffusion magnetic resonance imaging data from a multisite trial setting.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Fixel-based analysis was used to estimate microscopic fiber density, macroscopic fiber-bundle cross-section, and a combined fiber density and fiber-bundle cross-section measure within 45 cerebral and cerebellar tracts. Multivariate ANOVAs compared controls (<i>n</i> = 16), pre-ataxic (<i>n</i> = 10 SCA1, <i>n</i> = 24 SCA3), and ataxic patients (<i>n</i> = 14 SCA1, <i>n</i> = 36 SCA3). 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The receiver operating characteristic analyses revealed that cerebellar tracts resulted in greater area under the curve than cortico-spinal and transcallosal tracts.</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>These results demonstrate that fixel metrics offer sensitive disease-specific measures of early SCA disease state that correlate with standard clinical measures.</p>\n </section>\n \n <section>\n \n <h3> Trial Registration</h3>\n \n <p>Clinical Trial Readiness for SCA1 and SCA3 (READISCA), NCT03487367. https://clinicaltrials.gov/ct2/show/NCT03487367.</p>\n </section>\n </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1846-1857"},"PeriodicalIF":3.9000,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70116","citationCount":"0","resultStr":"{\"title\":\"Fixel-Based Analysis of Diffusion Imaging as a Quantitative Marker of Disease State in Spinocerebellar Ataxia\",\"authors\":\"David J. 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引用次数: 0
摘要
目的：脊髓小脑共济失调（SCAs）是一组遗传异质性的神经退行性疾病，可导致进行性恶化和生活质量下降。由于缺乏敏感的解剖、功能或基于扩散成像的生物标志物，治疗进展受到限制。本研究旨在利用来自多地点试验的扩散磁共振成像数据，确定失联前和早期SCA1和SCA3突变携带者大脑中的白质差异。方法：采用基于固定点的分析方法估计45个脑小脑束的微观纤维密度、宏观纤维束截面以及纤维密度和纤维束截面相结合的测量。多变量方差分析比较了对照组（n = 16）、共济失调前患者（n = 10 SCA1, n = 24 SCA3）和共济失调患者（n = 14 SCA1, n = 36 SCA3）。临床变量与固定指标相关，受试者操作特征分析发现白质束对区分对照与共济失调前SCA1和SCA3敏感。结果：我们发现，与对照组相比，在共济失调前和共济失调患者中，纤维密度、纤维束横截面和综合测量均存在广泛的白质缺陷，所有这些都与共济失调严重程度的临床测量相关。我们还发现，小脑束纤维密度和纤维束横截面的联合测量对SCA1（受者工作特征曲线下面积= 0.96）和SCA3（曲线下面积= 0.97）具有高灵敏度和特异性，可将对照与失调前区分开。受者操作特征分析显示，小脑束比皮质脊髓束和经胼胝体束产生更大的曲线下面积。解释：这些结果表明，固定指标提供了与标准临床指标相关的早期SCA疾病状态的敏感疾病特异性指标。试验注册：SCA1和SCA3临床试验准备（READISCA）， NCT03487367。https://clinicaltrials.gov/ct2/show/NCT03487367。
Fixel-Based Analysis of Diffusion Imaging as a Quantitative Marker of Disease State in Spinocerebellar Ataxia
Objective
Spinocerebellar ataxias (SCAs) are a group of genetically heterogeneous neurodegenerative diseases causing progressive deterioration and reduced quality of life. Therapeutic advances have been limited by a lack of sensitive anatomic, functional, or diffusion imaging-based biomarkers. This study aimed to identify white matter differences in the brains of preataxic and early-stage SCA1 and SCA3 mutation carriers using diffusion magnetic resonance imaging data from a multisite trial setting.
Methods
Fixel-based analysis was used to estimate microscopic fiber density, macroscopic fiber-bundle cross-section, and a combined fiber density and fiber-bundle cross-section measure within 45 cerebral and cerebellar tracts. Multivariate ANOVAs compared controls (n = 16), pre-ataxic (n = 10 SCA1, n = 24 SCA3), and ataxic patients (n = 14 SCA1, n = 36 SCA3). Clinical variables were correlated with fixel metrics and receiver operating characteristic analyses identified white matter tracts sensitive to distinguishing controls from pre-ataxic SCA1 and SCA3.
Results
We found widespread white matter deficits in pre-ataxic and ataxic patients compared to controls with regard to fiber density, fiber-bundle cross-section, and combined measures, all of which were associated with clinical measures of ataxia severity. We also found the combined fiber density and fiber-bundle cross-section measure from cerebellar tracts distinguished controls from pre-ataxia with high sensitivity and specificity for both SCA1 (receiver operating characteristic area under the curve = 0.96) and SCA3 (area under the curve = 0.97). The receiver operating characteristic analyses revealed that cerebellar tracts resulted in greater area under the curve than cortico-spinal and transcallosal tracts.
Interpretation
These results demonstrate that fixel metrics offer sensitive disease-specific measures of early SCA disease state that correlate with standard clinical measures.
Trial Registration
Clinical Trial Readiness for SCA1 and SCA3 (READISCA), NCT03487367. https://clinicaltrials.gov/ct2/show/NCT03487367.
期刊介绍：
Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.
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