Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA.
Department of Radiological Sciences, UCLA, Los Angeles, California, USA.
J Magn Reson Imaging. 2024 Oct;60(4):1484-1499. doi: 10.1002/jmri.29195. Epub 2024 Jan 11.
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.
To investigate iron dysregulation and microstructure alterations in subcortical regions as HD imaging biomarkers, and to associate such alterations with motor and cognitive impairments.
Prospective.
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, T-weighted imaging, quantitative susceptibility mapping, and diffusion tensor imaging.
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.
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.
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).
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.
2 TECHNICAL EFFICACY: Stage 2.
亨廷顿病（HD）的病理生理变化可在症状出现前数十年出现。需要强大的成像生物标志物来监测 HD 的进展，尤其是在临床发病前。
研究铁失调和皮质下区域的微观结构改变作为 HD 的成像生物标志物，并将这些改变与运动和认知障碍相关联。
前瞻性。
14 名有前驱 HD 的个体（38.0±11.0 岁，9 名女性；远发病例 N=6，近发病例 N=8），21 名有症状的 HD 患者（49.1±12.1 岁，11 名女性）和 33 名年龄匹配的健康对照者（43.9±12.2 岁，17 名女性）。
场强/序列：7T，T1 加权成像，定量磁化率映射和弥散张量成像。
在各组之间比较皮质下脑结构的体积，磁化率，各向异性分数（FA）和平均弥散度（MD），用于建立 HD 分类模型，并与临床测量和认知评估相关联。
广义线性模型，多元逻辑回归，接收器操作特性曲线下面积（AUC）和比较基于体积的模型与还包括磁化率和弥散度指标的模型的似然比检验，Wilcoxon 配对符号秩检验和 Pearson 相关。经 Benjamini-Hochberg 校正后 P 值<0.05 被认为具有统计学意义。
在萎缩之前，前驱和有症状的 HD 中纹状体的磁化率和 FA 均显著升高，即使在远发病例的前驱 HD 中也如此（壳核磁化率：0.027±0.022 比 0.018±0.013 ppm；FA：0.358±0.048 比 0.313±0.039）。当将前驱 HD 与 HC 区分开时，具有附加磁化率，FA 和 MD 特征的模型比仅基于体积的特征显示出更高的 AUC（0.83 比 0.66），而将有症状的 HD 与前驱 HD 区分开时，该模型显示出更高的 AUC（0.94 比 0.83）。纹状体的磁化率升高与 HD 中的认知恶化显著相关（执行功能：r=-0.600；社会情感功能：r=-0.486）。
7T MRI 显示了与 HD 进展相关的铁失调和微观结构改变，这些改变可能早于体积损失，对 HD 的鉴别具有额外的价值，并且可能与认知变化相关。
2 技术功效：2 级。
