Predicting neoadjuvant treatment response of locally advanced rectal cancer using co-registered endo-rectal photoacoustic and ultrasound imaging

2020年，全球直肠癌死亡人数超过33.9万人，新增病例73.2万人。从历史上看， II和III期肿瘤，也被称为局部晚期直肠癌(LARC)，已经通过外科手术治疗 切除、放疗和化疗。然而，新辅助(术前)治疗的进展现在使 高达35%的患者通过放疗和化疗实现肿瘤完全死亡或完全缓解 独自一人。在这些患者中，手术切除没有显示出任何好处，并带有重大的 并发症，恢复时间延长，生活质量下降。不幸的是，标准的临床测试和 放射学和内窥镜成像方法很难区分治疗后的疤痕和残留的疤痕 肿瘤。被治疗后的纤维化反应和水肿所困扰，当前技术的糟糕表现 这使得在手术前识别完整的应答者变得极其困难。由于这一技术差距， 手术切除仍然是专科三级护理中心以外的所有患者的标准护理(SOC)。 随着成像方式的改进，非手术治疗的广泛采用将减少治疗。 每年数以千计的直肠癌患者的发病率。一种很有希望的方式，光声成像，使用 血红蛋白作为一种内源性造影剂来绘制组织血管网络图。对于临床使用，我们有 开发并测试了一种新的联合配准的声学分辨率光声显微镜和超声(AR- PAM/US)内窥镜原型系统，以及深度学习神经网络分类器。初步测试 证实了一种独特的肿瘤完全反应的标志物--特别是正常粘膜血管的恢复 治疗后的肿瘤床内的结构。我们假设我们共同注册的AR-PAM/US系统和 神经网络分类器可以帮助外科医生检查残留的肿瘤微血管网络并评估直肠 肿瘤患者新辅助治疗后的病理完全反应。我们还假设序列AR- 在预测治疗完全缓解方面，PAM/US研究将显著优于SOC方法 结论并在治疗后监测中进行监测。 我们建议改进和优化我们的AR-PAM/US原型系统、探测器和软件，并对其进行优化 AR-PAM神经网络分类器准确区分完全应答者和残留者 癌症。我们将前瞻性地评估联合注册的AR-PAM/US技术改善SOC的能力 对一组LARC患者的治疗后风险管理和手术建议进行成像。我们会 还监测一组LARC患者，以确定联合注册的AR-PAM/US技术是否可以评估 肿瘤血管和血氧饱和度的变化并识别直肠癌的反应，两者在 治疗过程以及治疗后的监测。如果成功，这项技术将直接减少 减少直肠癌不必要的手术次数，提高生活质量。

In 2020, rectal cancer caused over 339,000 deaths globally, and 732,000 new cases were reported. Historically, Stage II and III tumors, also known as locally advanced rectal cancers (LARC), have been treated with surgical resection, radiation, and chemotherapy. However, advances in neoadjuvant (preoperative) treatment now enable up to 35% of patients to achieve complete tumor death, or complete response, with radiation and chemotherapy alone. In these individuals, surgical resection has shown no benefit and carries the significant risks of major complications, prolonged recovery, and reduced quality of life. Unfortunately, standard clinical testing and radiographic and endoscopic imaging modalities poorly differentiate post-treatment scars from the residual tumor. Confounded by post-treatment fibrotic reaction and edema, the poor performance of current technology makes it extremely difficult to identify complete responders before surgery. Due to this technological gap, surgical resection remains the standard of care (SOC) for all patients outside of specialized tertiary care centers. With improved imaging modalities, widespread adoption of nonoperative management would reduce treatment morbidity for thousands of rectal cancer patients annually. One promising modality, photoacoustic imaging, uses hemoglobin as an endogenous contrast agent to map tissue vascular networks. For clinical use, we have developed and tested a new co-registered acoustic resolution photoacoustic microscopy and ultrasound (AR- PAM/US) endoscopy prototype system, together with a deep learning neural network classifier. Initial testing demonstrated a unique marker of complete tumor response – specifically, recovery of normal mucosal vascular architecture within the treated tumor bed. We hypothesize that our co-registered AR-PAM/US system and the neural net classifiers can assist surgeons to examine the residual tumor microvessel network and assess rectal cancer patients’ pathologic complete response after neoadjuvant treatment. We also hypothesize that serial AR- PAM/US studies will perform significantly better than SOC methods in predicting complete response at treatment conclusion and during post-treatment surveillance. We propose to advance and optimize our prototype AR-PAM/US system, probe, and software and to optimize AR-PAM neural network classifiers to accurately differentiate complete responders from those with residual cancer. We will prospectively assess the ability of co-registered AR-PAM/US technology to improve SOC imaging in a cohort of LARC patients on post-treatment risk management and surgery recommendation. We will also monitor a group of LARC patients to determine if the co-registered AR-PAM/US technology can assess changes in tumor vascular and blood oxygen saturation and identify rectal cancer response, both during the course of treatment as well as in post-treatment surveillance. If successful, this technology will directly reduce the number of unnecessary surgeries for rectal cancer and improve quality of life.