Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina, United States of America.
Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina, United States of America.
PLoS One. 2020 Feb 25;15(2):e0225019. doi: 10.1371/journal.pone.0225019. eCollection 2020.
Small animal imaging has become essential in evaluating new cancer therapies as they are translated from the preclinical to clinical domain. However, preclinical imaging faces unique challenges that emphasize the gap between mouse and man. One example is the difference in breathing patterns and breath-holding ability, which can dramatically affect tumor burden assessment in lung tissue. As part of a co-clinical trial studying immunotherapy and radiotherapy in sarcomas, we are using micro-CT of the lungs to detect and measure metastases as a metric of disease progression. To effectively utilize metastatic disease detection as a metric of progression, we have addressed the impact of respiratory gating during micro-CT acquisition on improving lung tumor detection and volume quantitation. Accuracy and precision of lung tumor measurements with and without respiratory gating were studied by performing experiments with in vivo images, simulations, and a pocket phantom. When performing test-retest studies in vivo, the variance in volume calculations was 5.9% in gated images and 15.8% in non-gated images, compared to 2.9% in post-mortem images. Sensitivity of detection was examined in images with simulated tumors, demonstrating that reliable sensitivity (true positive rate (TPR) ≥ 90%) was achievable down to 1.0 mm3 lesions with respiratory gating, but was limited to ≥ 8.0 mm3 in non-gated images. Finally, a clinically-inspired "pocket phantom" was used during in vivo mouse scanning to aid in refining and assessing the gating protocols. Application of respiratory gating techniques reduced variance of repeated volume measurements and significantly improved the accuracy of tumor volume quantitation in vivo.
小动物成像在评估从临床前到临床领域的新癌症疗法方面变得至关重要。然而，临床前成像面临着独特的挑战，这些挑战强调了老鼠和人类之间的差距。一个例子是呼吸模式和屏气能力的差异，这会极大地影响肺部肿瘤负担的评估。作为一项研究肉瘤免疫治疗和放射治疗的合作临床试验的一部分，我们正在使用肺部 micro-CT 来检测和测量转移瘤，作为疾病进展的指标。为了有效地将转移性疾病检测作为进展的指标，我们已经解决了在 micro-CT 采集过程中呼吸门控对提高肺部肿瘤检测和体积定量的影响。通过对体内图像、模拟和口袋体模进行实验，研究了带有和不带有呼吸门控的肺部肿瘤测量的准确性和精密度。在体内进行测试-重测研究时，门控图像的体积计算方差为 5.9%，非门控图像的体积计算方差为 15.8%，而死后图像的体积计算方差为 2.9%。在模拟肿瘤图像中检查了检测的灵敏度，表明使用呼吸门控可以可靠地检测到 1.0mm3 大小的病变（真阳性率 (TPR) ≥ 90%），但在非门控图像中则限于≥8.0mm3 的病变。最后，在体内小鼠扫描过程中使用临床启发式的“口袋体模”来帮助完善和评估门控协议。应用呼吸门控技术可以减少重复体积测量的方差，并显著提高体内肿瘤体积定量的准确性。
