Altered Iron and Microstructure in Huntington's Disease Subcortical Nuclei: Insight From 7T MRI.
Altered Iron and Microstructure in Huntington's Disease Subcortical Nuclei: Insight From 7T MRI.
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DOI：
10.1002/jmri.29195
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发表时间：
2024-01
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通讯作者：
Jingwen Yao;Melanie A. Morrison;A. Jakary;Sivakami Avadiappan;Paul Rowley;Julia Glueck;Theresa Driscoll;Michael Geschwind;Alexandra Nelson;Kathrine L Possin;Duan Xu;C. Hess;J. Lupo
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作者：
Jingwen Yao;Melanie A. Morrison;A. Jakary;Sivakami Avadiappan;Paul Rowley;Julia Glueck;Theresa Driscoll;Michael Geschwind;Alexandra Nelson;Kathrine L Possin;Duan Xu;C. Hess;J. Lupo
背景亨廷顿病（HD）的病理生理学变化可先于症状发作数十年。需要稳健的成像生物标志物来监测HD进展，特别是在临床发作之前。目的探讨脑白质营养不良患者皮质下铁代谢紊乱和微结构改变作为脑白质营养不良影像学标志物的意义，并将其与运动和认知功能障碍联系起来。研究类型前瞻性。人群：14名表现前HD患者（38.0 ± 11.0岁，9名女性;远发型N = 6，近发型N = 8）、21名表现HD患者（49.1 ± 12.1岁，11名女性）和33名年龄匹配的健康对照（43.9 ± 12.2岁，17名女性）。场强/SEQUENCE 7 T、T1加权成像、定量磁化率标测和扩散张量成像。评估在各组之间比较皮质下脑结构内的体积、敏感性、各向异性分数（FA）和平均扩散率（MD），用于建立HD分类模型，并与临床测量和认知评估相关。广义线性模型、多变量逻辑回归、受试者操作特征与曲线下面积（AUC）、将体积模型与还包括易感性和扩散度量的模型进行比较的似然比检验、Wilcoxon配对符号秩检验和Pearson相关性。Benjamini-Hochberg校正后的P值<0.05被认为具有统计学显著性。结果：与对照组相比，在萎缩前的表现前和表现HD中，甚至在远离发病的表现前HD中，发现纹状体易感性和FA显著更高（壳核易感性：0.027 ± 0.022 vs. 0.018 ± 0.013 ppm; FA：0.358 ± 0.048 vs. 0.313 ± 0.039）。当区分表现前HD与HC（0.83 vs. 0.66）和表现与表现前HD（0.94 vs. 0.83）时，具有额外易感性、FA和MD特征的模型显示出比单独体积特征更高的AUC。高纹状体易感性与HD患者的认知功能恶化显著相关（执行功能：r = -0.600;社会情感功能：r = -0.486）。数据结论7 T MRI显示HD进展过程中的铁代谢紊乱和微结构改变，可能先于血容量减少，为HD的鉴别诊断提供参考，并可能与认知功能改变有关。证据水平2技术有效性：第2阶段。
BACKGROUND Pathophysiological changes of Huntington's disease (HD) can precede symptom onset by decades. Robust imaging biomarkers are needed to monitor HD progression, especially before the clinical onset. PURPOSE To investigate iron dysregulation and microstructure alterations in subcortical regions as HD imaging biomarkers, and to associate such alterations with motor and cognitive impairments. STUDY TYPE Prospective. POPULATION Fourteen individuals with premanifest HD (38.0 ± 11.0 years, 9 females; far-from-onset N = 6, near-onset N = 8), 21 manifest HD patients (49.1 ± 12.1 years, 11 females), and 33 age-matched healthy controls (43.9 ± 12.2 years, 17 females). FIELD STRENGTH/SEQUENCE 7 T, T1 -weighted imaging, quantitative susceptibility mapping, and diffusion tensor imaging. ASSESSMENT Volume, susceptibility, fractional anisotropy (FA), and mean diffusivity (MD) within subcortical brain structures were compared across groups, used to establish HD classification models, and correlated to clinical measures and cognitive assessments. STATISTICAL TESTS Generalized linear model, multivariate logistic regression, receiver operating characteristics with the area under the curve (AUC), and likelihood ratio test comparing a volumetric model to one that also includes susceptibility and diffusion metrics, Wilcoxon paired signed-rank test, and Pearson's correlation. A P-value <0.05 after Benjamini-Hochberg correction was considered statistically significant. RESULTS Significantly higher striatal susceptibility and FA were found in premanifest and manifest HD preceding atrophy, even in far-from-onset premanifest HD compared to controls (putamen susceptibility: 0.027 ± 0.022 vs. 0.018 ± 0.013 ppm; FA: 0.358 ± 0.048 vs. 0.313 ± 0.039). The model with additional susceptibility, FA, and MD features showed higher AUC compared to volume features alone when differentiating premanifest HD from HC (0.83 vs. 0.66), and manifest from premanifest HD (0.94 vs. 0.83). Higher striatal susceptibility significantly correlated with cognitive deterioration in HD (executive function: r = -0.600; socioemotional function: r = -0.486). DATA CONCLUSION 7 T MRI revealed iron dysregulation and microstructure alterations with HD progression, which could precede volume loss, provide added value to HD differentiation, and might be associated with cognitive changes. EVIDENCE LEVEL 2 TECHNICAL EFFICACY: Stage 2.