Sajjadi Amir Y, Isakoff Steven J, Deng Bin, Singh Bhawana, Wanyo Christy M, Fang Qianqian, Specht Michelle C, Schapira Lidia, Moy Beverly, Bardia Aditya, Boas David A, Carp Stefan A
Optics Division, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA; Department of Radiology, Harvard Medical School, Charlestown, MA 02129, USA; These authors contributed equally to this work;
Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA; These authors contributed equally to this work;
Biomed Opt Express. 2017 Jan 4;8(2):555-569. doi: 10.1364/BOE.8.000555. eCollection 2017 Feb 1.
We characterize novel breast cancer imaging biomarkers for monitoring neoadjuvant chemotherapy (NACT) and predicting outcome. Specifically, we recruited 30 patients for a pilot study in which NACT patients were imaged using dynamic tomographic optical breast imaging (DTOBI) to quantify the hemodynamic changes due to partial mammographic compression. DTOBI scans were obtained pre-treatment (referred to as day 0), as well as 7 and 30 days into therapy on female patients undergoing NACT. We present data for the 13 patients who participated in both day 0 and 7 measurements and had evaluable data, of which 7 also returned for day 30 measurements. We acquired optical images over 2 minutes following 4-8 lbs (18-36 N) of compression. The timecourses of tissue-volume averaged total hemoglobin (HbT), as well as hemoglobin oxygen saturation (SO) in the tumor vs. surrounding tissues were compared. Outcome prediction metrics based on the differential behavior in tumor vs. normal areas for responders (>50% reduction in maximum diameter) vs. non-responders were analyzed for statistical significance. At baseline, all patients exhibit an initial decrease followed by delayed recovery in HbT, and SO in the tumor area, in contrast to almost immediate recovery in surrounding tissue. At day 7 and 30, this contrast is maintained in non-responders; however, in responders, the contrast in hemodynamic time-courses between tumor and normal tissue starts decreasing at day 7 and substantially disappears at day 30. At day 30 into NACT, responding tumors demonstrate "normalization" of compression induced hemodynamics vs. surrounding normal tissue whereas non-responding tumors did not. This data suggests that DTOBI imaging biomarkers, which are governed by the interplay between tissue biomechanics and oxygen metabolism, may be suitable for guiding NACT by offering early predictions of treatment outcome.
我们对用于监测新辅助化疗（NACT）和预测治疗结果的新型乳腺癌成像生物标志物进行了特征描述。具体而言，我们招募了30名患者进行一项试点研究，在该研究中，对接受NACT的患者使用动态断层光学乳腺成像（DTOBI）进行成像，以量化因部分乳房X线摄影压迫导致的血流动力学变化。在接受NACT的女性患者治疗前（称为第0天）以及治疗第7天和第30天获得DTOBI扫描图像。我们展示了13名参与第0天和第7天测量且有可评估数据的患者的数据，其中7名患者还返回进行了第30天的测量。在施加4 - 8磅（18 - 36牛）的压迫后2分钟内采集光学图像。比较了肿瘤组织与周围组织中组织体积平均总血红蛋白（HbT）以及血红蛋白氧饱和度（SO）随时间的变化过程。分析了基于肿瘤与正常区域差异行为的反应者（最大直径减少>50%）与无反应者的结果预测指标的统计学意义。在基线时，所有患者的肿瘤区域HbT和SO均先出现初始下降，随后延迟恢复，而周围组织几乎立即恢复。在第7天和第30天，无反应者中这种差异仍然存在；然而，在反应者中，肿瘤与正常组织之间血流动力学时间过程的差异在第7天开始减小，并在第30天基本消失。在NACT治疗第30天时，有反应的肿瘤与周围正常组织相比，压迫诱导的血流动力学表现出“正常化”，而无反应的肿瘤则没有。这些数据表明，受组织生物力学和氧代谢相互作用支配的DTOBI成像生物标志物，可能通过提供治疗结果的早期预测来指导NACT。
