PDF(Pubmed)
Abstract：
Degeneration in the substantia nigra (SN) pars compacta (SNc) underlies motor symptoms in Parkinson\'s disease (PD). Currently, there are no neuroimaging biomarkers that are sufficiently sensitive, specific, reproducible, and accessible for routine diagnosis or staging of PD. Although iron is essential for cellular processes, it also mediates neurodegeneration. MRI can localize and quantify brain iron using magnetic susceptibility, which could potentially provide biomarkers of PD. We measured iron in the SNc, SN pars reticulata (SNr), total SN, and ventral tegmental area (VTA), using quantitative susceptibility mapping (QSM) and R2* relaxometry, in PD patients and age-matched healthy controls (HCs). PD patients, diagnosed within five years of participation and HCs were scanned at 3T (22 PD and 23 HCs) and 7T (17 PD and 21 HCs) MRI. Midbrain nuclei were segmented using a probabilistic subcortical atlas. QSM and R2* values were measured in midbrain subregions. For each measure, groups were contrasted, with Age and Sex as covariates, and receiver operating characteristic (ROC) curve analyses were performed with repeated k-fold cross-validation to test the potential of our measures to classify PD patients and HCs. Statistical differences of area under the curves (AUCs) were compared using the Hanley-MacNeil method (QSM versus R2*; 3T versus 7T MRI). PD patients had higher QSM values in the SNc at both 3T (padj = 0.001) and 7T (padj = 0.01), but not in SNr, total SN, or VTA, at either field strength. No significant group differences were revealed using R2* in any midbrain region at 3T, though increased R2* values in SNc at 7T MRI were marginally significant in PDs compared to HCs (padj = 0.052). ROC curve analyses showed that SNc iron measured with QSM, distinguished early PD patients from HCs at the single-subject level with good diagnostic accuracy, using 3T (mean AUC = 0.83, 95 % CI = 0.82-0.84) and 7T (mean AUC = 0.80, 95 % CI = 0.79-0.81) MRI. Mean AUCs reported here are from averages of tests in the hold-out fold of cross-validated samples. The Hanley-MacNeil method demonstrated that QSM outperforms R2* in discriminating PD patients from HCs at 3T, but not 7T. There were no significant differences between 3T and 7T in diagnostic accuracy of QSM values in SNc. This study highlights the importance of segmenting midbrain subregions, performed here using a standardized atlas, and demonstrates high accuracy of SNc iron measured with QSM at 3T MRI in identifying early PD patients. QSM measures of SNc show potential for inclusion in neuroimaging diagnostic biomarkers of early PD. An MRI diagnostic biomarker of PD would represent a significant clinical advance.
摘要：
黑质（SN）致密部（SNc）变性是帕金森病（PD）运动症状的基础。目前,没有足够敏感的神经成像生物标志物，具体,可重复,并且可以进行PD的常规诊断或分期。尽管铁对细胞过程至关重要，它还介导神经变性。MRI可以使用磁化率定位和量化脑铁，这可能提供PD的生物标志物。我们在SNc中测量了铁，SN网状结构(SNr)，总SN,腹侧被盖区（VTA），使用定量磁化率图(QSM)和R2*弛豫法，PD患者和年龄匹配的健康对照（HCs）。PD患者,在参与后5年内诊断并在3T(22PD和23HC)和7T(17PD和21HC)MRI扫描HC。使用概率皮质下图谱分割中脑核。在中脑亚区测量QSM和R2*值。对于每一项措施，组进行了对比，以年龄和性别为协变量，和受试者工作特征(ROC)曲线分析进行了重复k倍交叉验证,以检验我们的措施对PD患者和HC进行分类的潜力.使用Hanley-MacNeil方法(QSM对R2*;3T对7TMRI)比较曲线下面积(AUC)的统计学差异。PD患者在3T（padj=0.001）和7T（padj=0.01）的SNc中具有较高的QSM值，但不是在SNR，总SN,或VTA，在任一场强下。在3T时，在任何中脑区域使用R2*均未发现显着组间差异，尽管在7TMRI时SNc的R2*值增加，但与HC相比，PD中的R2*值略有差异（padj=0.052）。ROC曲线分析表明,用QSM测定SNc铁,在单受试者水平上区分早期PD患者与HCs，具有良好的诊断准确性，使用3T（平均AUC=0.83，95％CI=0.82-0.84）和7T（平均AUC=0.80，95％CI=0.79-0.81）MRI。此处报告的平均AUC来自交叉验证样品的保留折叠中的测试平均值。Hanley-MacNeil方法证明，在3T时，QSM在区分PD患者与HC方面优于R2*，但不是7T。在SNc中QSM值的诊断准确性在3T和7T之间没有显着差异。这项研究强调了分割中脑亚区的重要性，在这里使用标准化的地图集进行表演，并证明了在3TMRI下用QSM测量的SNc铁在识别早期PD患者中的高准确性。SNc的QSM测量显示出可能包含在早期PD的神经影像学诊断生物标志物中。PD的MRI诊断生物标志物将代表显著的临床进步。
