用扩散模型统一建模脑影像多变量参考分布,实现可扩展的异常检测。
Denoising diffusion networks for normative modeling in neuroimaging
- 用扩散模型联合建模多个脑影像特征,保留变量间复杂依赖关系。
- 在2~200维数据上表现优于传统方法,高维下仍保持良好校准性。
- 适合需要多指标联合分析的神经影像研究者,尤其关注异常评分标准化。
规范建模通过条件于协变量的生物测量参考分布,生成百分位数和临床可解释的偏离分数。现有神经影像流程对每个影像衍生表型(IDP)单独建模,虽可扩展但忽略了多变量依赖关系所编码的协同模式。本文提出使用去噪扩散概率模型(DDPM)作为表格型IDP的统一条件密度估计器,通过采样生成单变量百分位数与偏离分数。采用两种去噪器骨干:(i) 特征自适应线性调制(FiLM)的MLP,(ii) 带特征自注意力与样本间注意力的表格变压器(SAINT),通过学习嵌入条件化协变量。在含异方差与多模态年龄效应的合成基准及英国生物银行FreeSurfer表型数据集上评估,维度从2到200。评估包括百分位校准(绝对百分位误差、经验覆盖度、概率积分变换)、分布保真度(柯尔莫戈洛夫-斯米尔诺夫检验)、多变量依赖诊断与最近邻记忆分析。低维时,扩散模型输出校准效果接近传统基线并联合建模真实依赖结构;高维时,变压器骨干显著优于MLP,更好保留高阶依赖,支持可扩展的联合规范建模,同时兼容标准单变量流程。结果表明,基于扩散的规范建模是实现神经影像中校准多变量偏离图谱的实用路径。
原文摘要 · Abstract (English)
Normative modeling estimates reference distributions of biological measures conditional on covariates, enabling centiles and clinically interpretable deviation scores to be derived. Most neuroimaging pipelines fit one model per imaging-derived phenotype (IDP), which scales well but discards multivariate dependence that may encode coordinated patterns. We propose denoising diffusion probabilistic models (DDPMs) as a unified conditional density estimator for tabular IDPs, from which univariate centiles and deviation scores are derived by sampling. We utilise two denoiser backbones: (i) a feature-wise linear modulation (FiLM) conditioned multilayer perceptron (MLP) and (ii) a tabular transformer with feature self-attention and intersample attention (SAINT), conditioning covariates through learned embeddings. We evaluate on a synthetic benchmark with heteroscedastic and multimodal age effects and on UK Biobank FreeSurfer phenotypes, scaling from dimension of 2 to 200. Our evaluation suite includes centile calibration (absolute centile error, empirical coverage, and the probability integral transform), distributional fidelity (Kolmogorov-Smirnov tests), multivariate dependence diagnostics, and nearest-neighbour memorisation analysis. For low dimensions, diffusion models deliver well-calibrated per-IDP outputs comparable to traditional baselines while jointly modeling realistic dependence structure. At higher dimensions, the transformer backbone remains substantially better calibrated than the MLP and better preserves higher-order dependence, enabling scalable joint normative models that remain compatible with standard per-IDP pipelines. These results support diffusion-based normative modeling as a practical route to calibrated multivariate deviation profiles in neuroimaging.
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