Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
J Alzheimers Dis. 2018;64(2):393-404. doi: 10.3233/JAD-180118.
PET imaging is an established technique to detect cerebral amyloid-β (Aβ) plaques in vivo. Some preclinical and postmortem data report an accumulation of redox-active iron near Aβ plaques. Quantitative susceptibility mapping (QSM) at high-field MRI enables iron deposits to be depicted with high spatial resolution.
Aim of this study was to examine whether iron and Aβ plaque accumulation is related and thus, whether 7T MRI might be an additive diagnostic tool to Aβ PET imaging.
Postmortem human Alzheimer's disease (AD) and healthy control (HC) frontal gray matter (GM) was imaged with 7T MRI which resulted in T1 maps and QSM. Aβ plaque load was determined by histopathology. In vivo, 10 Aβ PET-positive AD patients (74.1±6.0a) and 10 Aβ PET-negative HCs (67.1±4.4a) underwent 7T MR examination and QSM maps were analyzed. Severity of cognitive deficits was determined by MMSE.
Postmortem, the susceptibility of Aβ plaque-containing GM were higher than those of Aβ plaque-free GM (0.011±0.002 versus - 0.008±0.003 ppm, p < 0.001). In vivo, only the bilateral globus pallidus showed significantly higher susceptibility in AD patients compared to HCs (right: 0.277±0.018 versus - 0.009±0.009 ppm; left: 0.293±0.014 versus - 0.007±0.012 ppm, p < 0.0001). The pallidal QSM values were negatively correlated with those of the MMSE (r = - 0.69, p = 0.001).
The postmortem study revealed significant susceptibility differences between the Aβ plaque-containing and Aβ plaque-free GM, whereas in vivo only the QSM values of the globus pallidus differed significantly between AD and HC group. The pallidal QSM values correlated with the severity of cognitive deficits. These findings encourage efforts to optimize the 7T-QSM methodology.
正电子发射断层扫描(PET)成像是一种用于在体内检测脑淀粉样蛋白-β(Aβ)斑块的成熟技术。一些临床前和尸检数据报告称,氧化还原活性铁在 Aβ 斑块附近积聚。高磁场磁共振成像的定量磁化率映射(QSM)可以高空间分辨率描绘铁沉积物。
本研究旨在探讨铁和 Aβ 斑块积聚是否相关,因此,7T MRI 是否可能成为 Aβ PET 成像的附加诊断工具。
对死后阿尔茨海默病(AD)和健康对照(HC)额叶灰质(GM)进行 7T MRI 成像,获得 T1 图谱和 QSM。通过组织病理学确定 Aβ 斑块负荷。在体内,10 名 Aβ PET 阳性 AD 患者(74.1±6.0a)和 10 名 Aβ PET 阴性 HC(67.1±4.4a)接受了 7T MR 检查,并分析了 QSM 图谱。认知功能障碍的严重程度通过 MMSE 确定。
死后,含有 Aβ 斑块的 GM 的磁化率高于不含 Aβ 斑块的 GM(0.011±0.002 对-0.008±0.003 ppm,p<0.001)。在体内,只有双侧苍白球在 AD 患者中与 HC 相比表现出显著更高的磁化率(右侧:0.277±0.018 对-0.009±0.009 ppm;左侧:0.293±0.014 对-0.007±0.012 ppm,p<0.0001)。苍白球的 QSM 值与 MMSE 呈负相关(r=-0.69,p=0.001)。
尸检研究显示,Aβ 斑块含量和 Aβ 斑块含量之间存在显著的磁化率差异,而体内仅 AD 和 HC 组之间苍白球的 QSM 值存在显著差异。苍白球的 QSM 值与认知功能障碍的严重程度相关。这些发现鼓励努力优化 7T-QSM 方法。