Associations of quantitative susceptibility mapping with Alzheimer's disease clinical and imaging markers.
Associations of quantitative susceptibility mapping with Alzheimer's disease clinical and imaging markers.
复制标题
定量敏感性映射与阿尔茨海默氏病临床和成像标记的关联。
DOI：
10.1016/j.neuroimage.2020.117433
复制
发表时间：
2021-01-01
期刊：
影响因子：
5.7
通讯作者：
Jack CR Jr
中科院分区：
文献类型：
--
作者：
Cogswell PM;Wiste HJ;Senjem ML;Gunter JL;Weigand SD;Schwarz CG;Arani A;Therneau TM;Lowe VJ;Knopman DS;Botha H;Graff-Radford J;Jones DT;Kantarci K;Vemuri P;Boeve BF;Mielke MM;Petersen RC;Jack CR Jr
据推测，铁代谢的改变与阿尔茨海默病的病理学有关，之前的研究已经表明铁负荷与β淀粉样斑块之间存在关联。定量磁化率图 (QSM) 是最近流行的 MR 技术，用于推断继发于铁和其他矿物质存在的局部组织磁化率。 QSM 值越大意味着组织中的铁浓度越高。 QSM 已被用于研究脑铁负荷与阿尔茨海默氏病既定标志物之间的关系，但其关系仍不清楚。在这项工作中，我们研究了 QSM 信号特征以及 QSM 测量的敏感性与已建立的阿尔茨海默病临床和成像标志物之间的关联。该研究包括来自梅奥诊所衰老和阿尔茨海默病研究中心的 421 名参与者（234 名男性，中位年龄 70 岁，范围 34-97 岁）； 296 人（70%）被诊断为认知未受损，69 人（16%）被诊断为轻度认知障碍，56 人（13%）被诊断为遗忘性痴呆。所有参与者均进行了多回波梯度回忆回波成像、PiB 淀粉样蛋白 PET 和 Tauvid tau PET。方差成分分析表明，参与者的皮质敏感性差异较低。线性回归模型适合评估与区域易感性的关联。随着年龄的增长，深部和下灰核（苍白球、壳核、黑质、底丘脑核）的易感性随着年龄的增长和认知障碍的增加而增加（年龄增加 10 岁，β 值：0.0017 至 0.0053 ppm，p = 0.03 至 < 0.001；β 值：0.0021 至 0.0058 ppm，年龄增加 10 岁）。心理状态短期测试降低 5 分，p = 0.003 至 p < 0.001）。皮质区域的效应较小，且与年龄的相关性通常呈负相关。较高的易感性与苍白球和壳核中较高的淀粉样蛋白 PET SUVR 显着相关（淀粉样蛋白 PET 增加 20% 时，β 值分别为 0.0029 和 0.0012 ppm，p = 0.05 和 0.02），基底神经节中较高的 tau PET，其中苍白球中的效应量最大（对于淀粉样蛋白 PET 增加 20%，β 值分别为 0.0082 ppm）。 tau PET 增加 20%，p < 0.001），并且内侧颞叶皮质灰质体积较低（0.0006 ppm，体积减少 20%，p = 0.03）。总体而言，这些发现表明，深部和下部灰核，特别是苍白球和壳核的敏感性，可能是认知能力下降、淀粉样蛋白沉积和 tau 配体脱靶结合的标志。尽管铁已被证明存在于淀粉样斑块中并且与神经退行性变相关，但使用 QSM 的实施在皮层中的铁含量不足以可靠地检测到。
Altered iron metabolism has been hypothesized to be associated with Alzheimer’s disease pathology, and prior work has shown associations between iron load and beta amyloid plaques. Quantitative susceptibility mapping (QSM) is a recently popularized MR technique to infer local tissue susceptibility secondary to the presence of iron as well as other minerals. Greater QSM values imply greater iron concentration in tissue. QSM has been used to study relationships between cerebral iron load and established markers of Alzheimer’s disease, however relationships remain unclear. In this work we study QSM signal characteristics and associations between susceptibility measured on QSM and established clinical and imaging markers of Alzheimer’s disease. The study included 421 participants (234 male, median age 70 years, range 34–97 years) from the Mayo Clinic Study of Aging and Alzheimer’s Disease Research Center; 296 (70%) had a diagnosis of cognitively unimpaired, 69 (16%) mild cognitive impairment, and 56 (13%) amnestic dementia. All participants had multi-echo gradient recalled echo imaging, PiB amyloid PET, and Tauvid tau PET. Variance components analysis showed that variation in cortical susceptibility across participants was low. Linear regression models were fit to assess associations with regional susceptibility. Expected increases in susceptibility were found with older age and cognitive impairment in the deep and inferior gray nuclei (pallidum, putamen, substantia nigra, subthalamic nucleus) (betas: 0.0017 to 0.0053 ppm for a 10 year increase in age, p = 0.03 to < 0.001; betas: 0.0021 to 0.0058 ppm for a 5 point decrease in Short Test of Mental Status, p = 0.003 to p < 0.001). Effect sizes in cortical regions were smaller, and the age associations were generally negative. Higher susceptibility was significantly associated with higher amyloid PET SUVR in the pallidum and putamen (betas: 0.0029 and 0.0012 ppm for a 20% increase in amyloid PET, p = 0.05 and 0.02, respectively), higher tau PET in the basal ganglia with the largest effect size in the pallidum (0.0082 ppm for a 20% increase in tau PET, p < 0.001), and with lower cortical gray matter volume in the medial temporal lobe (0.0006 ppm for a 20% decrease in volume, p = 0.03). Overall, these findings suggest that susceptibility in the deep and inferior gray nuclei, particularly the pallidum and putamen, may be a marker of cognitive decline, amyloid deposition, and off-target binding of the tau ligand. Although iron has been demonstrated in amyloid plaques and in association with neurodegeneration, it is of insufficient quantity to be reliably detected in the cortex using this implementation of QSM.
登录
查看更多内容
定量敏感性映射以评估阿尔茨海默氏病的早期阶段。
DOI：
10.1016/j.nicl.2017.08.019
发表时间：
2017
期刊：
NeuroImage. Clinical
影响因子：
--
作者：
Kim HG;Park S;Rhee HY;Lee KM;Ryu CW;Rhee SJ;Lee SY;Wang Y;Jahng GH
通讯作者：
Jahng GH
DOI：
10.1098/rsif.2014.0165
发表时间：
2014-06-06
期刊：
Journal of the Royal Society, Interface
影响因子：
--
作者：
Everett J;Céspedes E;Shelford LR;Exley C;Collingwood JF;Dobson J;van der Laan G;Jenkins CA;Arenholz E;Telling ND
通讯作者：
Telling ND
影响因子：
3.7
作者：
Acosta-Cabronero J;Williams GB;Cardenas-Blanco A;Arnold RJ;Lupson V;Nestor PJ
通讯作者：
Nestor PJ
影响因子：
11.2
作者：
Klunk, WE;Engler, H;Långström, B
通讯作者：
Långström, B
DOI：
10.1073/pnas.0610821104
发表时间：
2007-07-10
影响因子：
11.1
作者：
Duyn, Jeff H.;van Gelderen, Peter;Fukunaga, Masaki
通讯作者：
Fukunaga, Masaki