Yang Aocai, Du Lei, Gao Wenwen, Liu Bing, Chen Yue, Wang Yige, Liu Xiuxiu, Lv Kuan, Zhang Wenwei, Xia Hui, Wu Kai, Ma Guolin
Department of Radiology, China-Japan Friendship Hospital, Beijing, China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Quant Imaging Med Surg. 2022 Sep;12(9):4570-4586. doi: 10.21037/qims-22-7.
In Alzheimer's disease (AD), cerebral iron accumulation colocalizes with the pathological proteins amyloid-β (Aβ) and tau. Furthermore, tau-induced cortical thinning is associated with cognitive decline. In this study, quantitative susceptibility mapping (QSM) was used to investigate the whole-brain distribution pattern of cortical iron deposition and its relationships with cognition and cortical thickness in AD.
This cross-sectional study prospectively recruited 30 participants with AD and 26 age- and sex-matched healthy controls (HCs). All participants underwent QSM and T-weighted examinations on a 3.0T MRI scanner. Global cognition was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Whole-brain cross-sectional QSM analysis and whole-brain QSM regression analyses against the MMSE and MoCA scores were performed. Surface-based morphometry analysis was also performed. Subsequently, in regions with significant atrophy, magnetic susceptibility was compared between the AD and HC groups, and the association between magnetic susceptibility and cortical thickness was assessed.
Whole-brain QSM cross-sectional analysis in the AD group demonstrated widespread increased susceptibility across the cortical ribbon, asymmetrically covering the left hemisphere cerebral cortex, caudate nucleus, putamen, and partial cerebellar cortex. Whole-brain QSM regression analyses in the AD group showed that increased susceptibility covaried with lower MMSE and MoCA scores, and was predominantly located in the right parietal cortex and lateral occipital cortex. In the AD group, cortical thickness was reduced in the left superior temporal gyrus, right frontal pole, fusiform gyus, and pars opercularis, and there were increases in susceptibility in the right frontal pole (AD: mean ± SD 0.034±0.007 ppm, 95% CI: 0.032-0.037 ppm; HC: 0.030±0.005 ppm, 95% CI: 0.028-0.032 ppm; P=0.016) and pars opercularis (AD: 0.020±0.003 ppm, 95% CI: 0.018-0.021 ppm; HC: 0.017±0.002 ppm, 95% CI: 0.017-0.018 ppm; P=0.002). Susceptibility was negatively correlated with cortical thickness in the right pars opercularis in the entire cohort (r=-0.521, P<0.001) and AD group (r=-0.510, P=0.005).
Widespread cortical iron, as measured by QSM, accumulated in AD and iron deposition was associated with poor cognitive performance. Increased iron content was also associated with brain atrophy. Our study suggests QSM may be a useful imaging biomarker for monitoring the neurodegenerative progression of AD.
在阿尔茨海默病（AD）中，脑铁沉积与病理蛋白β-淀粉样蛋白（Aβ）和tau蛋白共定位。此外，tau蛋白诱导的皮质变薄与认知功能下降有关。在本研究中，采用定量磁化率成像（QSM）来研究AD患者皮质铁沉积的全脑分布模式及其与认知和皮质厚度的关系。
这项横断面研究前瞻性招募了30名AD患者和26名年龄及性别匹配的健康对照者（HCs）。所有参与者均在3.0T磁共振成像（MRI）扫描仪上接受QSM和T加权检查。使用简易精神状态检查表（MMSE）和蒙特利尔认知评估量表（MoCA）评估整体认知功能。进行了全脑横断面QSM分析以及针对MMSE和MoCA评分的全脑QSM回归分析。还进行了基于表面的形态测量分析。随后，在存在明显萎缩的区域，比较AD组和HC组之间的磁化率，并评估磁化率与皮质厚度之间的关联。
AD组的全脑QSM横断面分析显示，整个皮质带的磁化率普遍增加，不对称地覆盖左半球大脑皮质、尾状核、壳核和部分小脑皮质。AD组的全脑QSM回归分析表明，磁化率增加与较低的MMSE和MoCA评分相关，且主要位于右侧顶叶皮质和枕外侧皮质。在AD组中，左侧颞上回、右侧额极、梭状回和岛盖部的皮质厚度降低，右侧额极（AD：均值±标准差0.034±0.007 ppm，95%置信区间：0.032 - 0.037 ppm；HC：0.030±0.005 ppm，95%置信区间：0.028 - 0.032 ppm；P = 0.016）和岛盖部（AD：0.020±0.003 ppm，95%置信区间：0.018 - 0.021 ppm；HC：0.017±0.002 ppm，95%置信区间：0.017 - 0.018 ppm；P = 0.002）的磁化率增加。在整个队列（r = -0.521，P < 0.001）和AD组（r = -0.510，P = 0.005）中，右侧岛盖部的磁化率与皮质厚度呈负相关。
通过QSM测量，AD患者存在广泛的皮质铁沉积，铁沉积与认知功能差有关。铁含量增加也与脑萎缩有关。我们的研究表明，QSM可能是监测AD神经退行性进展的一种有用的成像生物标志物。
