用贝叶斯方法评估影像生物标志物的可重复性,助力精准治疗响应分析。
Generalizing imaging biomarker repeatability studies using Bayesian inference: Applications in detecting heterogeneous treatment response in whole-body diffusion-weighted MRI of metastatic prostate cancer
- 基于贝叶斯框架,灵活建模多种分布类型,提升测量不确定性评估能力。
- 在两组转移性前列腺癌患者中发现约70%肿瘤对治疗有反应。
- 适用于多种影像模态,特别适合研究异质性治疗反应的临床研究。
影像生物标志物的评估对推动精准医学和改善疾病表征至关重要。尽管已有方法可用于提取影像中的疾病异质性指标,但评估测量不确定性的稳健框架仍不成熟。为此,我们提出一种新的贝叶斯框架,用于评估生物标志物研究中疾病异质性度量的精确性。该方法通过哈密顿蒙特卡洛采样,扩展了传统方法的统计假设灵活性,支持对正态分布及狄利克雷-多项式分布等变量的分析,可在不同模型假设下推导生物标志物参数的后验分布。该框架适用于多种成像模态和生物标志物类型,为可重复、客观的生物标志物评价提供通用基础。为验证其应用价值,我们将其应用于全身体积扩散加权MRI(WBDWI),评估转移性骨病的异质性治疗反应。具体分析了两项针对转移性去势抵抗性前列腺癌(mCRPC)治疗的研究数据。结果表明,在两个研究中,个体肿瘤的响应率约为70%,客观刻画了系统治疗的差异化反应,验证了该方法的临床相关性。该贝叶斯框架为多模态影像生物标志物研究提供了强大工具,并为mCRPC治疗反应分析提供关键洞见。
原文摘要 · Abstract (English)
The assessment of imaging biomarkers is critical for advancing precision medicine and improving disease characterization. Despite the availability of methods to derive disease heterogeneity metrics in imaging studies, a robust framework for evaluating measurement uncertainty remains underdeveloped. To address this gap, we propose a novel Bayesian framework to assess the precision of disease heterogeneity measures in biomarker studies. Our approach extends traditional methods for evaluating biomarker precision by providing greater flexibility in statistical assumptions and enabling the analysis of biomarkers beyond univariate or multivariate normally-distributed variables. Using Hamiltonian Monte Carlo sampling, the framework supports both, for example, normally-distributed and Dirichlet-Multinomial distributed variables, enabling the derivation of posterior distributions for biomarker parameters under diverse model assumptions. Designed to be broadly applicable across various imaging modalities and biomarker types, the framework builds a foundation for generalizing reproducible and objective biomarker evaluation. To demonstrate utility, we apply the framework to whole-body diffusion-weighted MRI (WBDWI) to assess heterogeneous therapeutic responses in metastatic bone disease. Specifically, we analyze data from two patient studies investigating treatments for metastatic castrate-resistant prostate cancer (mCRPC). Our results reveal an approximately 70% response rate among individual tumors across both studies, objectively characterizing differential responses to systemic therapies and validating the clinical relevance of the proposed methodology. This Bayesian framework provides a powerful tool for advancing biomarker research across diverse imaging-based studies while offering valuable insights into specific clinical applications, such as mCRPC treatment response.
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