Wiest Roland, Burgunder Jean-Marc, Kiefer Claus
Support Center of Advanced Neuroimaging (SCAN), Institute for Diagnostic and Interventional Neuroradiology, University of Bern, Inselspital, University Hospital, Bern, Switzerland.
Neurology, University of Bern, Inselspital, University Hospital, Bern, Switzerland.
Front Neurol. 2017 Sep 6;8:465. doi: 10.3389/fneur.2017.00465. eCollection 2017.
Huntington's disease (HD) is a chronic progressive neurodegenerative disorder with a long presymptomatic period that opens a window for potential therapies aimed at neuroprotection. Neuroimaging offers the potential to monitor disease-related progression of the disease burden (DB) using model-based magnetization transfer imaging.
We have conducted a cross-sectional study to stratify healthy age-matched controls, premanifest and symptomatic HD patients ( = 30) according to their macromolecular depositions in the caudate nucleus. We employed a binary spin-bath magnetization transfer (MT) method for a quantitative description of macromolecule deposits and interactions with their adjacent environment.
A region-of-interest based fuzzy clustering analysis identified representative clusters for several stages of the disease course related to its progression: one cluster represented subjects with a high DB <268 that encompassed all symptomatic HD patients and one presymptomatic gene carrier. The next cluster represented the presymptomatic gene carriers with a very low DB >230 and healthy controls. Three further clusters represented transition zones between both DB levels (230-268) consisting of presymptomatic carriers with DB values increasing with decreasing distance from the cluster that indicated low DB and healthy age-matched controls.
The proposed binary spin-bath MT method offers the potential to monitor DB and progression in HD. The method may augment qualitative MT techniques since it depicts tissue changes related to interactions between macromolecules and protons in disease specific brain regions that follow the neurodegenerative process.
亨廷顿舞蹈症（HD）是一种慢性进行性神经退行性疾病，有较长的症状前期，这为旨在进行神经保护的潜在治疗打开了一扇窗。神经成像技术利用基于模型的磁化传递成像，有潜力监测疾病负担（DB）的疾病相关进展。
我们进行了一项横断面研究，根据尾状核中的大分子沉积情况，对年龄匹配的健康对照、症状前期和症状性HD患者（n = 30）进行分层。我们采用二元自旋浴磁化传递（MT）方法对大分子沉积物及其与相邻环境的相互作用进行定量描述。
基于感兴趣区域的模糊聚类分析确定了与疾病进展相关的几个病程阶段的代表性聚类：一个聚类代表DB值高<268的受试者，包括所有症状性HD患者和一名症状前期基因携带者。下一个聚类代表DB值非常低>230的症状前期基因携带者和健康对照。另外三个聚类代表两个DB水平（230 - 268）之间的过渡区，由DB值随着与表示低DB的聚类和年龄匹配的健康对照的距离减小而增加的症状前期携带者组成。
所提出的二元自旋浴MT方法有潜力监测HD中的DB和疾病进展。该方法可能增强定性MT技术，因为它描绘了与疾病特定脑区中大分子和质子之间相互作用相关的组织变化，这些变化遵循神经退行性过程。
