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首页> 美国卫生研究院文献>Translational Oncology >Diffusion-Weighted MRI as a Biomarker of Tumor Radiation Treatment Response Heterogeneity: A Comparative Study of Whole-Volume Histogram Analysis versus Voxel-Based Functional Diffusion Map Analysis
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Diffusion-Weighted MRI as a Biomarker of Tumor Radiation Treatment Response Heterogeneity: A Comparative Study of Whole-Volume Histogram Analysis versus Voxel-Based Functional Diffusion Map Analysis

机译：弥散加权MRI作为肿瘤放射治疗反应异质性的生物标记：全体积直方图分析与基于体素的功能性扩散图分析的比较研究

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RATIONALE: Treatment of glioblastoma (GBM) remains challenging due in part to its histologic intratumoral heterogeneity that contributes to its overall poor treatment response. Our goal was to evaluate a voxel-based biomarker, the functional diffusion map (fDM), as an imaging biomarker to detect heterogeneity of tumor response in a radiation dose escalation protocol using a genetically engineered murine GBM model. EXPERIMENTAL DESIGN: Twenty-four genetically engineered murine GBM models [Ink4a-Arf-/-/Ptenloxp/loxp/Ntv-a RCAS/PDGF(+)/Cre(+)] were randomized in four treatment groups (n = 6 per group) consisting of daily doses of 0, 1, 2, and 4 Gy delivered for 5 days. Contrast-enhanced T1-weighted and diffusion-weighted magnetic resonance imaging (MRI) scans were acquired for tumor delineation and quantification of apparent diffusion coefficient (ADC) maps, respectively. MRI experiments were performed daily for a week and every 2 days thereafter. For each animal, the area under the curve (AUC) of the percentage change of the ADC (AUCADC) and that of the increase in fDM values (AUCfDM+) were determined within the first 5 days following therapy initiation. RESULTS: Animal survival increased with increasing radiation dose. Treatment induced a dose-dependent increase in tumor ADC values. The strongest correlation between survival and ADC measurements was observed using the AUCfDM+ metric (R2 = 0.88). CONCLUSION: This study showed that the efficacy of a voxel-based imaging biomarker (fDM) was able to detect spatially varying changes in tumors, which were determined to be a more sensitive predictor of overall response versus whole-volume tumor measurements (AUCADC). Finally, fDM provided for visualization of treatment-associated spatial heterogeneity within the tumor.
机译：理由：胶质母细胞瘤（GBM）的治疗仍然具有挑战性，部分原因是其组织学上的肿瘤内异质性，导致其总体治疗反应较差。我们的目标是评估一种基于体素的生物标记物，即功能扩散图（fDM），作为一种成像生物标记物，以使用基因工程鼠类GBM模型在辐射剂量递增方案中检测肿瘤反应的异质性。实验设计：二十四个基因工程鼠类GBM模型[Ink4a-Arf -/- / Pten loxp / loxp / Ntv-a RCAS / PDGF（+）/ Cre（ +）]随机分为四个治疗组（每组n = 6），分别由每日剂量为0、1、2和4 Gy的5天组成。分别进行对比增强的T1加权和弥散加权磁共振成像（MRI）扫描，以描绘肿瘤并量化表观弥散系数（ADC）图。每天进行MRI实验，持续一周，之后每2天进行一次。对于每只动物，在治疗开始后的前5天内确定ADC百分比变化的曲线下面积（AUCADC）和fDM值增加的曲线下面积（AUCfDM +）。结果：动物存活率随辐射剂量的增加而增加。治疗引起肿瘤ADC值的剂量依赖性增加。使用AUCfDM +度量（R 2 = 0.88）观察到生存与ADC测量之间的最强相关性。结论：这项研究表明，基于体素的成像生物标志物（fDM）的功效能够检测肿瘤的空间变化，这些变化被确定为总反应与整体肿瘤测量（AUCADC）相比更敏感的预测指标。最后，fDM提供了可视化的肿瘤内与治疗相关的空间异质性。

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