Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Maindy Road, Cardiff, CF 24 4HQ, UK.
Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Maindy Road, Cardiff, CF 24 4HQ, UK.
Neuroimage Clin. 2021;30:102658. doi: 10.1016/j.nicl.2021.102658. Epub 2021 Apr 5.
White matter (WM) alterations have been identified as a relevant pathological feature of Huntington's disease (HD). Increasing evidence suggests that WM changes in this disorder are due to alterations in myelin-associated biological processes. Multi-compartmental analysis of the complex gradient-echo MRI signal evolution in WM has been shown to quantify myelin in vivo, therefore pointing to the potential of this technique for the study of WM myelin changes in health and disease. This study first characterized the reproducibility of metrics derived from the complex multi-echo gradient-recalled echo (mGRE) signal across the corpus callosum in healthy participants, finding highest reproducibility in the posterior callosal segment. Subsequently, the same analysis pipeline was applied in this callosal region in a sample of premanifest HD patients (n = 19) and age, sex and education matched healthy controls (n = 21). In particular, we focused on two myelin-associated derivatives: i. the myelin water signal fraction (f), a parameter dependent on myelin content; and ii. The difference in frequency between myelin and intra-axonal water pools (Δω), a parameter dependent on the ratio between the inner and the outer axonal radii. f was found to be lower in HD patients (β = -0.13, p = 0.03), while Δω did not show a group effect. Performance in tests of working memory, executive function, social cognition and movement was also assessed, and a greater age-related decline in executive function was detected in HD patients (β = -0.06, p = 0.006), replicating previous evidence of executive dysfunction in HD. Finally, the correlation between f, executive function, and proximity to disease onset was explored in patients, and a positive correlation between executive function and f was detected (r = 0.542; p = 0.02). This study emphasises the potential of complex mGRE signal analysis for aiding understanding of HD pathogenesis and progression. Moreover, expanding on evidence from pathology and animal studies, it provides novel in vivo evidence supporting myelin breakdown as an early feature of HD.
脑白质（WM）改变已被确定为亨廷顿病（HD）的一个重要病理特征。越来越多的证据表明，这种疾病中的 WM 变化是由于髓鞘相关生物过程的改变。对 WM 中复杂梯度回波 MRI 信号演化的多腔室分析已被证明可在体内定量测量髓鞘，因此指出该技术在研究健康和疾病中的 WM 髓鞘变化方面具有潜力。本研究首先描述了在健康参与者的胼胝体中，从复杂的多回波梯度回波（mGRE）信号中得出的指标的可重复性，在后胼胝体段的可重复性最高。随后，将相同的分析管道应用于该胼胝体区域的一组前表现 HD 患者（n=19）和年龄、性别和教育程度匹配的健康对照者（n=21）。特别是，我们集中研究了两个与髓鞘相关的衍生物：i. 髓鞘水信号分数（f），一个依赖于髓鞘含量的参数；ii. 髓鞘和轴内水池之间的频率差（Δω），一个依赖于内轴和外轴半径比的参数。f 在 HD 患者中较低（β=-0.13，p=0.03），而 Δω 未显示组间差异。还评估了工作记忆、执行功能、社会认知和运动的测试表现，并且在 HD 患者中检测到执行功能的年龄相关性下降更大（β=-0.06，p=0.006），复制了 HD 中执行功能障碍的先前证据。最后，在患者中探讨了 f、执行功能和与疾病发作的接近程度之间的相关性，并且检测到执行功能与 f 之间存在正相关（r=0.542；p=0.02）。这项研究强调了复杂 mGRE 信号分析在辅助理解 HD 发病机制和进展方面的潜力。此外，它扩展了病理学和动物研究的证据，提供了新的体内证据支持髓鞘破坏作为 HD 的早期特征。
