van Bergen J M G, Hua J, Unschuld P G, Lim I A L, Jones C K, Margolis R L, Ross C A, van Zijl P C M, Li X
From the Departments of Radiology and Radiological Sciences (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.) F.M. Kirby Research Center for Functional Brain Imaging (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.), Kennedy Krieger Institute, Baltimore, Maryland
From the Departments of Radiology and Radiological Sciences (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.) F.M. Kirby Research Center for Functional Brain Imaging (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.), Kennedy Krieger Institute, Baltimore, Maryland.
AJNR Am J Neuroradiol. 2016 May;37(5):789-96. doi: 10.3174/ajnr.A4617. Epub 2015 Dec 17.
In patients with premanifest (nonsymptomatic) and advanced Huntington disease, changes in brain iron levels in the basal ganglia have been previously reported, especially in the striatum. Quantitative susceptibility mapping by using MR phase imaging allows in vivo measurements of tissue magnetic susceptibility, which has been shown to correlate well with iron levels in brain gray matter and is believed to be more specific than other imaging-based iron measures. The purpose of this study was to investigate the use of magnetic susceptibility as a biomarker of disease progression.
Fifteen subjects with premanifest Huntington disease and 16 age-matched healthy controls were scanned at 7T. Magnetic susceptibility, effective relaxation, and tissue volume in deep gray matter structures were quantified and compared with genetic and clinical measures.
Subjects with premanifest Huntington disease showed significantly higher susceptibility values in the caudate nucleus, putamen, and globus pallidus, indicating increased iron levels in these structures. Significant decreases in magnetic susceptibility were found in the substantia nigra and hippocampus. In addition, significant volume loss (atrophy) and an increase effective relaxation were observed in the caudate nucleus and putamen. Susceptibility values in the caudate nucleus and putamen were found to be inversely correlated with structure volumes and directly correlated with the genetic burdens, represented by cytosine-adenine-guanine repeat age-product-scaled scores.
The significant magnetic susceptibility differences between subjects with premanifest Huntington disease and controls and their correlation with genetic burden scores indicate the potential use of magnetic susceptibility as a biomarker of disease progression in premanifest Huntington disease.
先前已有报道称，在临床前期（无症状）和晚期亨廷顿病患者中，基底神经节的脑铁水平会发生变化，尤其是在纹状体中。利用磁共振相位成像进行的定量磁化率成像能够在体内测量组织磁化率，研究表明，该磁化率与脑灰质中的铁水平密切相关，且被认为比其他基于成像的铁测量方法更具特异性。本研究的目的是探究磁化率作为疾病进展生物标志物的用途。
对15名临床前期亨廷顿病患者和16名年龄匹配的健康对照者进行了7T磁共振扫描。对深部灰质结构的磁化率、有效弛豫和组织体积进行了量化，并与基因和临床指标进行了比较。
临床前期亨廷顿病患者在尾状核、壳核和苍白球中的磁化率值显著更高，表明这些结构中的铁水平升高。黑质和海马中的磁化率显著降低。此外，尾状核和壳核出现了显著的体积损失（萎缩）以及有效弛豫增加。发现尾状核和壳核中的磁化率值与结构体积呈负相关，与以胞嘧啶 - 腺嘌呤 - 鸟嘌呤重复年龄 - 乘积 - 缩放分数表示的基因负担呈正相关。
临床前期亨廷顿病患者与对照者之间显著的磁化率差异及其与基因负担分数的相关性表明，磁化率有可能作为临床前期亨廷顿病疾病进展的生物标志物。
