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：本研究旨在通过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）的响应，并筛选可用于早期评估治疗效果的磁共振成像参数作为潜在生物标志物。 研究方法：将CT26.WT结肠腺癌肿瘤接种于BALB/c小鼠后肢皮下进行生长。治疗方案为：静脉注射光敏剂Bremachlorin，于给药6小时后对肿瘤实施10分钟激光照射（激光功率密度为200 mW/cm²）。分别于基线、光动力疗法（PDT）后即刻、24小时及72小时进行7 T磁共振成像扫描。于每个时间点定量测定肿瘤弛豫时间常数（T1、T2）及表观扩散系数（apparent diffusion coefficient, ADC）。此外，采用标准Tofts-Kermode示踪动力学模型，通过Gd-DOTA动态对比增强（dynamic contrast-enhanced, DCE）磁共振成像估算转运常数（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）染色开展组织学分析，以表征肿瘤活性。 研究结果：与未治疗对照组相比，该疗法诱导肿瘤发生广泛细胞死亡，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。肿瘤表观扩散系数（ADC）值于24小时及72小时显著升高。动态对比增强磁共振成像（DCE-MRI）衍生的示踪动力学参数可早期反映治疗响应。光动力疗法（PDT）后即刻，肿瘤大部分区域出现完全血管闭塞，剩余肿瘤组织的对比剂摄取降低（转运常数Ktrans下降）。治疗后24小时，多数肿瘤基本无对比剂摄取。在接受2周随访的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：动态对比增强磁共振成像（DCE-MRI）可有效可视化光动力疗法（PDT）后的血管效应。于光动力疗法（PDT）后24至72小时测定的内源性对比参数T1、T2及ADC，亦可作为评估治疗效果的潜在生物标志物。