Data from: Quantitative multi-parametric magnetic resonance imaging of tumor response to photodynamic therapy

Objective: The aim of this study was to characterize response to photodynamic therapy (PDT) in a mouse cancer model using a multi-parametric quantitative MRI protocol and to identify MR parameters as potential biomarkers for early assessment of treatment outcome. Methods: CT26.WT colon carcinoma tumors were grown subcutaneously in the hind limb of BALB/c mice. Therapy consisted of intravenous injection of the photosensitizer Bremachlorin, followed by 10 min laser illumination (200 mW/cm2) of the tumor 6 h post injection. MRI at 7 T was performed at baseline, directly after PDT, as well as at 24 h, and 72 h. Tumor relaxation time constants (T1 and T2) and apparent diffusion coefficient (ADC) were quantified at each time point. Additionally, Gd-DOTA dynamic contrast-enhanced (DCE) MRI was performed to estimate transfer constants (Ktrans) and volume fractions of the extravascular extracellular space (ve) using standard Tofts-Kermode tracer kinetic modeling. At the end of the experiment, tumor viability was characterized by histology using NADH-diaphorase staining. Results: The therapy induced extensive cell death in the tumor and resulted in significant reduction in tumor growth, as compared to untreated controls. Tumor T1 and T2 relaxation times remained unchanged up to 24 h, but decreased at 72 h after treatment. Tumor ADC values significantly increased at 24 h and 72 h. DCE-MRI derived tracer kinetic parameters displayed an early response to the treatment. Directly after PDT complete vascular shutdown was observed in large parts of the tumors and reduced uptake (decreased Ktrans) in remaining tumor tissue. At 24 h, contrast uptake in most tumors was essentially absent. Out of 5 animals that were monitored for 2 weeks after treatment, 3 had tumor recurrence, in locations that showed strong contrast uptake at 72 h. Conclusion: DCE-MRI is an effective tool for visualization of vascular effects directly after PDT. Endogenous contrast parameters T1, T2, and ADC, measured at 24 to 72 h after PDT, are also potential biomarkers for evaluation of therapy outcome.研究目的：本研究旨在采用多参数定量磁共振成像（magnetic resonance imaging, MRI）方案，表征小鼠癌症模型对光动力疗法（photodynamic therapy, PDT）的应答反应，并筛选可用于早期评估治疗结局的磁共振参数作为潜在生物标志物。实验方法：将CT26.WT结肠癌细胞株接种于BALB/c小鼠后肢皮下构建移植瘤模型。治疗方案为静脉注射光敏剂Bremachlorin，于给药后6小时对肿瘤实施10分钟激光照射（照射功率密度为200 mW/cm²）。分别于基线、光动力疗法（PDT）即刻、给药后24小时及72小时行7特斯拉（7 T）磁共振成像（MRI）扫描。于各时间点定量检测肿瘤的弛豫时间常数（T1、T2）及表观扩散系数（apparent diffusion coefficient, ADC）。此外，采用标准Tofts-Kermode示踪剂动力学模型，通过Gd-DOTA动态增强磁共振成像（dynamic contrast-enhanced MRI, DCE-MRI）估算转运常数（Ktrans）及血管外细胞外间隙体积分数（ve）。实验结束时，通过烟酰胺腺嘌呤二核苷酸黄递酶（NADH-diaphorase）染色的组织病理学分析评估肿瘤活性。实验结果：与未处理对照组相比，该治疗可诱导肿瘤内广泛细胞死亡，并显著抑制肿瘤生长。肿瘤T1、T2弛豫时间在24小时内无显著变化，但于治疗后72小时出现下降。肿瘤ADC值在24小时及72小时均显著升高。动态增强磁共振成像（DCE-MRI）衍生的示踪剂动力学参数可较早反映治疗应答。PDT即刻即可观察到肿瘤大部分区域的血管完全闭塞，剩余肿瘤组织的对比剂摄取量降低（Ktrans值下降）。治疗后24小时，多数肿瘤几乎无对比剂摄取。于治疗后随访2周的5只小鼠中，3只出现肿瘤复发，复发部位均为72小时时对比剂摄取较强的区域。研究结论：动态增强磁共振成像（DCE-MRI）是可视化评估PDT即刻血管效应的有效工具。于PDT后24~72小时检测的内源性对比参数T1、T2及ADC，同样可作为评估治疗结局的潜在生物标志物。