用扩散模型生成假数据,提升阿尔茨海默病预测准确率
Pretraining Transformer-Based Models on Diffusion-Generated Synthetic Graphs for Alzheimer's Disease Prediction
- 用扩散模型生成平衡类别的合成临床数据
- 在合成数据上预训练图注意力模型,再迁移到真实数据
- 适合小样本、类别不平衡的医疗诊断研究者
阿尔茨海默病早期精准检测对干预和预后至关重要。但受限于标注数据少、多中心异质性和类别不平衡,构建可靠的机器学习模型面临挑战。本文提出一种基于Transformer的诊断框架,结合基于扩散的合成数据生成、图表示学习与迁移学习。在真实世界NACC数据集上训练条件扩散概率模型(DDPM),生成大规模且符合多模态临床与神经影像特征分布的合成队列,同时平衡诊断类别。针对不同模态的图Transformer编码器在该合成数据上预训练,学习鲁棒的判别性表征,随后冻结编码器,在原始NACC数据上训练神经分类器。通过最大均值差异(MMD)、弗雷歇距离和能量距离等指标量化真实与合成队列的分布一致性,并辅以校准性和固定特异性敏感性分析。实证表明,该框架优于标准基线,包括早期/晚期融合深度网络和多模态图模型MaGNet,于NACC数据集上实现更高AUC、准确率、敏感性和特异性,验证了基于扩散的合成预训练在低样本、不平衡临床预测中的泛化优势。
原文摘要 · Abstract (English)
Early and accurate detection of Alzheimer's disease (AD) is crucial for enabling timely intervention and improving outcomes. However, developing reliable machine learning (ML) models for AD diagnosis is challenging due to limited labeled data, multi-site heterogeneity, and class imbalance. We propose a Transformer-based diagnostic framework that combines diffusion-based synthetic data generation with graph representation learning and transfer learning. A class-conditional denoising diffusion probabilistic model (DDPM) is trained on the real-world NACC dataset to generate a large synthetic cohort that mirrors multimodal clinical and neuroimaging feature distributions while balancing diagnostic classes. Modality-specific Graph Transformer encoders are first pretrained on this synthetic data to learn robust, class-discriminative representations and are then frozen while a neural classifier is trained on embeddings from the original NACC data. We quantify distributional alignment between real and synthetic cohorts using metrics such as Maximum Mean Discrepancy (MMD), Frechet distance, and energy distance, and complement discrimination metrics with calibration and fixed-specificity sensitivity analyses. Empirically, our framework outperforms standard baselines, including early and late fusion deep neural networks and the multimodal graph-based model MaGNet, yielding higher AUC, accuracy, sensitivity, and specificity under subject-wise cross-validation on NACC. These results show that diffusion-based synthetic pretraining with Graph Transformers can improve generalization in low-sample, imbalanced clinical prediction settings.
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