Imaging iron and neuromelanin simultaneously using a single 3D gradient echo magnetization transfer sequence: Combining neuromelanin, iron and the nigrosome-1 sign as complementary imaging biomarkers in early stage Parkinson's disease
Imaging iron and neuromelanin simultaneously using a single 3D gradient echo magnetization transfer sequence: Combining neuromelanin, iron and the nigrosome-1 sign as complementary imaging biomarkers in early stage Parkinson's disease
复制标题
使用单个 3D 梯度回波磁化转移序列同时对铁和神经黑色素进行成像：将神经黑色素、铁和 nigrosome-1 标志组合作为早期帕金森病的互补成像生物标志物
DOI：
10.1016/j.neuroimage.2021.117810
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发表时间：
2021-02-05
期刊：
影响因子：
5.7
通讯作者：
Haacke, E. Mark
中科院分区：
文献类型：
--
作者：
He, Naying;Ghassaban, Kiarash;Haacke, E. Mark
早期诊断帕金森病（PD）仍然是一个临床挑战。以前的研究使用铁，神经黑色素（NM）或黑质（SN）中的Nigrosome-1（N1）符号本身已经无法提供足够高的诊断性能，这些方法被临床采用。我们在这项研究中的目标是提取NM复合体积，铁含量和体积代表整个SN，和N1的迹象作为潜在的互补成像生物标志物使用一个单一的3D磁化传递对比（MTC）梯度回波序列，并评估其诊断性能和早期PD的临床相关性。共40例早期特发性PD受试者和40例年龄和性别匹配的健康对照（HC）在3 T下成像。使用动态规划（DP）边界检测算法半自动确定NM边界（代表SN延髓部（SNpc）和臂旁色素核）和铁边界（代表总SN（SNpc和SN网状部））。进行受试者操作特征分析以评估这些成像生物标志物在诊断早期PD中的效用。相关分析被用来研究这些影像学指标与临床量表之间的关系。我们还引入了NM和总铁重叠体积的概念，以证明NM相对于含铁SN的损失。此外，所有80例病例均独立评估了N1征。与HC相比，PD受试者的NM和SN体积较低，而SN中的铁含量较高。有趣的是，双侧N1征缺失的PD受试者铁含量最高。单次测量的两个半球平均值的曲线下面积（AUC）值为：NM复合体体积为0.960;总SN体积为0.788; SN铁含量为0.740，N1符号为0.891。通过二元逻辑回归将NM复合体体积与以下各项测量组合，得到平均右侧和左侧的AUC值：总铁含量为0.976;总SN体积为0.969，重叠体积为0.965，N1符号为0.983。我们发现SN体积与CRISPR-III之间呈负相关（R-2 = 0.22，p = 0.002）。虽然N1体征表现良好，但它不包含任何有关铁含量或NM的定量信息，因此，将此体征与NM和铁测量结合，可以更好地解释PD受试者中N1体征消失时发生的情况。总之，NM复合体体积、SN体积、铁含量和如从单个MTC序列导出的N1标志的组合为理解和诊断早期PD提供了补充信息。
Diagnosing early stage Parkinson's disease (PD) is still a clinical challenge. Previous studies using iron, neuromelanin (NM) or the Nigrosome-1 (N1) sign in the substantia nigra (SN) by themselves have been unable to provide sufficiently high diagnostic performance for these methods to be adopted clinically. Our goal in this study was to extract the NM complex volume, iron content and volume representing the entire SN, and the N1 sign as potential complementary imaging biomarkers using a single 3D magnetization transfer contrast (MTC) gradient echo sequence and to evaluate their diagnostic performance and clinical correlations in early stage PD. A total of 40 early stage idiopathic PD subjects and 40 age- and sex-matched healthy controls (HCs) were imaged at 3T. NM boundaries (representing the SN pars compacta (SNpc) and parabrachial pigmented nucleus) and iron boundaries representing the total SN (SNpc and SN pars reticulata) were determined semi-automatically using a dynamic programming (DP) boundary detection algorithm. Receiver operating characteristic analyses were performed to evaluate the utility of these imaging biomarkers in diagnosing early stage PD. A correlation analysis was used to study the relationship between these imaging measures and the clinical scales. We also introduced the concept of NM and total iron overlap volumes to demonstrate the loss of NM relative to the iron containing SN. Furthermore, all 80 cases were evaluated for the N1 sign independently. The NM and SN volumes were lower while the iron content was higher in the SN for PD subjects compared to HCs. Interestingly, the PD subjects with bilateral loss of the N1 sign had the highest iron content. The area under the curve (AUC) values for the average of both hemispheres for single measures were: .960 for NM complex volume; .788 for total SN volume; .740 for SN iron content and .891 for the N1 sign. Combining NM complex volume with each of the following measures through binary logistic regression led to AUC values for the averaged right and left sides of: .976 for total iron content; .969 for total SN volume, .965 for overlap volume and .983 for the N1 sign. We found a negative correlation between SN volume and UPDRS-III (R-2 = .22, p = .002). While the N1 sign performed well, it does not contain any information about iron content or NM quantitatively, therefore, marrying this sign with the NM and iron measures provides a better physiological explanation of what is happening when the N1 sign disappears in PD subjects. In summary, the combination of NM complex volume, SN volume, iron content and the N1 sign as derived from a single MTC sequence provides complementary information for understanding and diagnosing early stage PD.