arXiv:2606.12658cs.LGq-bio.QM2026-06

PINN用物理约束建模化疗药物分布,既补全了测不到的组织浓度,又暴露了传统方法隐藏的参数不可辨识问题。

Physics-Informed Neural Networks for Chemotherapy Pharmacokinetics: Benchmarking the Clinical Estimator and Exposing Parameter Identifiability

论文配图:Physics-Informed Neural Networks for Chemotherapy Pharmacokinetics: Benchmarking the Clinical Estimator and Exposing Parameter Identifiability
图 1 · 摘自论文原文
  • 用物理方程约束神经网络,从血浆数据推算组织药物浓度
  • 在非线性消除模型中揭示参数不可辨识性,传统方法却会给出错误结果
  • 仅需少量组织采样即可显著提升估计精度,适合临床药代动力学研究

物理信息神经网络(PINNs)适用于生物学中已知动态但部分变量无法观测的问题。化疗药代动力学(PK)是典型场景:血浆浓度可测,但决定肿瘤杀伤和毒性反应的组织浓度无法直接获取。本文将PINN与标准临床基准(基于解析双指数解的非线性最小二乘法,简称NLS)及纯数据驱动的MLP对比。在两室线性模型中,NLS接近最优,而PINN在单次训练中即匹配其性能并输出组织曲线,数据仅靠的MLP则在组织预测上误差约10倍。在米氏消除扩展模型中,因无解析解,NLS误设模型且返回无意义速率常数。而PINN揭示该模型仅凭血浆数据不可辨识,收敛至k12→0的解。加入两次稀疏组织观测后,五次随机种子下,PINN对k21估计误差小于1%,Vmax、Km在1个标准差内,k12从0.02提升至0.82(仍低约2个标准差),而传统方法因依赖双指数假设无法实现此类估计。

原文摘要 · Abstract (English)

Physics-Informed Neural Networks (PINNs) are an attractive tool for partial-observation problems in biology, where the governing dynamics are known but some compartments cannot be measured. Chemotherapy pharmacokinetics (PK) is a clean instance: drug concentration in plasma is routinely measured, but concentration in tissue -- which determines tumour kill and off-target toxicity -- is not. We benchmark a PINN against the standard clinical baseline (nonlinear least-squares on the analytical biexponential plasma solution, hereafter NLS) and a physics-agnostic neural baseline (a data-only MLP) on two PK problems. On the linear two-compartment problem, NLS is near-optimal; the PINN matches it to within a small constant factor while also producing the tissue curve in a single training pass, whereas the data-only MLP fails on tissue by roughly 10x. On a Michaelis-Menten extension (saturable elimination), the biexponential closed form no longer exists, so NLS is mis-specified and silently returns meaningless rate constants. The PINN instead exposes a deeper fact: the Michaelis-Menten two-compartment model is non-identifiable from plasma alone, and the PINN reports this honestly by converging to a basin with k12 -> 0. Adding two sparse tissue observations largely resolves identifiability: across five seeds the PINN recovers k21 to within 1% of truth and Vmax, Km to within one standard-deviation bar, while k12 moves in the correct direction (0.02 -> 0.82) but remains ~2 sigma below truth -- a recovery the closed-form NLS estimator cannot attempt at all, because its biexponential ansatz describes only plasma. Our claim is not that PINNs beat NLS. It is that PINNs offer a uniform recipe that ties the textbook estimator on the textbook problem, exposes structural identifiability that the textbook estimator hides, and absorbs heterogeneous measurements within a single loss.

药代动力学物理信息网络参数辨识化疗建模

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