Robust parametric modeling of Alzheimer's disease progression.

Robust parametric modeling of Alzheimer's disease progression.
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DOI:
10.1016/j.neuroimage.2020.117460
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发表时间:
2021-01-15
期刊:
影响因子:
5.7
通讯作者:
Sorensen, Lauge
Sorensen, Lauge
中科院分区:
医学1区
文献类型:
--
作者:
Ghazi, Mostafa Mehdipour;Nielsen, Mads;Pai, Akshay;Modat, Marc;Cardoso, M. Jorge;Ourselin, Sebastien;Sorensen, Lauge

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使用纵向数据对疾病进展进行定量表征可以为个体的病理阶段提供长期预测。本工作研究了使用参数化方法对阿尔茨海默病进展的鲁棒建模。所提出的方法线性映射的个人的年龄的疾病进展评分(DPS),并共同适合约束广义逻辑函数的纵向动态的生物标志物作为DPS的功能,使用M-估计。估计的鲁棒性通过蒙特卡洛回归使用自举来量化,并且拟合函数的估计拐点用于对疾病过程中的建模生物标志物进行时间排序。核密度估计应用于获得的DPS的临床状态分类使用贝叶斯分类器。不同的M-估计量和逻辑函数,包括本研究中提出的一种新类型,称为修改的标准,对阿尔茨海默病神经成像倡议(ADNI)的数据进行评估,用于体积磁共振成像(MRI)和正电子发射断层扫描(PET)生物标志物,脑脊液(CSF)测量以及认知测试的鲁棒建模。结果显示,使用逻辑损失拟合的修改的Stannard函数实现了最佳建模性能,在所有生物标志物和自助程序中的平均归一化平均绝对误差(NMAE)为0.991。应用于ADNI测试集,该模型在临床状态分类中实现了0.934的多类ROC曲线下面积(AUC)。所提出的模型获得的结果在预测生物标志物值和分类临床状态方面优于几乎所有最先进的结果。最后,实验表明,使用丰富的ADNI数据训练的所提出的模型可以很好地推广到来自国家阿尔茨海默氏症协调中心(NACC)的数据,平均NMAE为1.182,多类AUC为0.929。
Quantitative characterization of disease progression using longitudinal data can provide long-term predictions for the pathological stages of individuals. This work studies the robust modeling of Alzheimer’s disease progression using parametric methods. The proposed method linearly maps the individual’s age to a disease progression score (DPS) and jointly fits constrained generalized logistic functions to the longitudinal dynamics of biomarkers as functions of the DPS using M-estimation. Robustness of the estimates is quantified using bootstrapping via Monte Carlo resampling, and the estimated inflection points of the fitted functions are used to temporally order the modeled biomarkers in the disease course. Kernel density estimation is applied to the obtained DPSs for clinical status classification using a Bayesian classifier. Different M-estimators and logistic functions, including a novel type proposed in this study, called modified Stannard, are evaluated on the data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) for robust modeling of volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET) biomarkers, cerebrospinal fluid (CSF) measurements, as well as cognitive tests. The results show that the modified Stannard function fitted using the logistic loss achieves the best modeling performance with an average normalized mean absolute error (NMAE) of 0.991 across all biomarkers and bootstraps. Applied to the ADNI test set, this model achieves a multiclass area under the ROC curve (AUC) of 0.934 in clinical status classification. The obtained results for the proposed model outperform almost all state-of-the-art results in predicting biomarker values and classifying clinical status. Finally, the experiments show that the proposed model, trained using abundant ADNI data, generalizes well to data from the National Alzheimer’s Coordinating Center (NACC) with an average NMAE of 1.182 and a multiclass AUC of 0.929.
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