Mixed longitudinal and cross-sectional analyses of deep gray matter and white matter using diffusion weighted images in premanifest and manifest Huntington's disease.
Mixed longitudinal and cross-sectional analyses of deep gray matter and white matter using diffusion weighted images in premanifest and manifest Huntington's disease.
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应用弥散加权成像对预显和显亨廷顿病患者深部灰质和白色物质进行纵向和横断面混合分析
DOI：
10.1016/j.nicl.2023.103493
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发表时间：
2023
影响因子：
4.2
通讯作者：
Faria, Andreia, V
中科院分区：
文献类型：
--
作者：
Hu, Beini;Younes, Laurent;Bu, Xuan;Liu, Chin-Fu;Ratnanather, J. Tilak;Paulsen, Jane;Georgiou-Karistianis, Nellie;Miller, Michael I.;Ross, Christopher;Faria, Andreia, V
深部灰质较深部白色物质变化更明显、更早。深白色物质的上级区和后部变化更早、更明显。亨廷顿氏病除了影响衰老外，还可能影响大脑的微观结构。HD的白色物质和深部灰质表现出区域和时间的脆弱性。亨廷顿病（HD）患者的大脑变化在临床发作前开始年就开始了，因此识别生物标志物以跟踪这些早期变化仍然至关重要。从弥散加权磁共振成像（DTI）的张量建模中导出的指示微观大脑结构的MRI可以为区域体积测量添加重要信息。本研究使用两个大规模纵向多中心数据集，PREDICT-HD和IMAGE-HD，追踪具有广泛CAP评分（CAG重复扩增和年龄的产物）的HD参与者的DTI变化，包括那些患有预显疾病（即，在临床发作之前）。利用全自动数据驱动的方法来研究划分为感兴趣区域的整个大脑，我们使用S形和线性回归模型跟踪DTI指标（扩散率和各向异性分数）与CAP评分的变化。我们使用变点分析确定了S形回归中的拐点。与深层白色物质相比，深层灰质的DTI指标变化更明显，更早。在深层白色物质中，这些变化更明显，并且与前部和下部区域相比，在上级和后部区域发生更早。在固定CAP评分范围内，HD受试者的平均扩散率与年龄的曲线与对照组不同，表明该疾病对微观大脑结构的年龄有额外影响。这些结果表明，区域和时间的白色物质和深部灰质的脆弱性，在HD的实验治疗的潜在影响。
Deep gray matter showed more evident and earlier changes than deep white matter. Superior and posterior areas of deep white matter changed earlier and more evidently. Huntington’s disease may affect the microscopic brain structure in addition to aging. White matter and deep gray matter in HD exhibits regional and temporal vulnerability. Changes in the brain of patients with Huntington's disease (HD) begin years before clinical onset, so it remains critical to identify biomarkers to track these early changes. Metrics derived from tensor modeling of diffusion-weighted MRIs (DTI), that indicate the microscopic brain structure, can add important information to regional volumetric measurements. This study uses two large-scale longitudinal, multicenter datasets, PREDICT-HD and IMAGE-HD, to trace changes in DTI of HD participants with a broad range of CAP scores (a product of CAG repeat expansion and age), including those with pre-manifest disease (i.e., prior to clinical onset). Utilizing a fully automated data-driven approach to study the whole brain divided in regions of interest, we traced changes in DTI metrics (diffusivity and fractional anisotropy) versus CAP scores, using sigmoidal and linear regression models. We identified points of inflection in the sigmoidal regression using change-point analysis. The deep gray matter showed more evident and earlier changes in DTI metrics over CAP scores, compared to the deep white matter. In the deep white matter, these changes were more evident and occurred earlier in superior and posterior areas, compared to anterior and inferior areas. The curves of mean diffusivity vs. age of HD participants within a fixed CAP score were different from those of controls, indicating that the disease has an additional effect to age on the microscopic brain structure. These results show the regional and temporal vulnerability of the white matter and deep gray matter in HD, with potential implications for experimental therapeutics.
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影响因子：
4.2
作者：
Benitez A;Jensen JH;Falangola MF;Nietert PJ;Helpern JA
通讯作者：
Helpern JA
影响因子：
4.2
作者：
Mueller, Hans-Peter;Groen, Georg;Sprengelmeyer, Reiner;Kassubek, Jan;Ludolph, Albert C.;Hobbs, Nicola;Cole, James;Roos, Raymund A. C.;Duerr, Alexandra;Tabrizi, Sarah J.;Landwehrmeyer, G. Bernhard;Suessmuth, Sigurd D.
通讯作者：
Suessmuth, Sigurd D.
影响因子：
3.5
作者：
Langbehn, DR;Brinkman, RR;Hayden, MR
通讯作者：
Hayden, MR
影响因子：
10.5
作者：
Dominguez, Juan F.;Stout, Julie C.;Georgiou-Karistianis, Nellie
通讯作者：
Georgiou-Karistianis, Nellie
影响因子：
4.4
作者：
Falangola, Maria F.;Jensen, Jens H.;Babb, James S.;Hu, Caixia;Castellanos, Francisco X.;Di Martino, Adriana;Ferris, Steven H.;Helpern, Joseph A.
通讯作者：
Helpern, Joseph A.