SBIR Phase I: Intraoperative Detection and Ablation of Microscopic Residual Cancer in the Tumor Bed

该小型企业创新研究第一阶段项目将开发一种术中激光消融设备，以同时检测和治疗大块切除肿瘤后肿瘤床中残留的癌细胞。目前，外科医生将切除的肿瘤组织送到病理学检查，以确定手术边缘是否清除（干净）癌细胞。如果边缘不干净，患者必须返回进行第二次手术。我们开发了一种荧光分子成像剂和一种宽视场成像装置，以单细胞分辨率检测残留癌细胞。表面被激光照射，成像剂使癌细胞在非常特定的波长下发出荧光。在这个NSF赞助的项目中，我们建议将消融技术结合到这个成像系统中，以便在手术过程中实时检测和消除检测到的残留癌细胞。具体来说，我们将把消融技术结合到我们的激光成像系统中，记录癌症目标的像素位置，用激光摧毁目标，并提供反馈确认。该项目的更广泛影响/商业潜力是改善患者护理和降低医疗成本。目前，大约50%的乳腺癌患者和35%的肉瘤患者需要第二次肿瘤减瘤手术，因为最终病理报告在初次手术后几天返回，表明残留的癌细胞已留在患者体内。此外，25%的最终病理学报告没有检测到残留的癌细胞，这是由于该过程中固有的采样误差。因此，大多数患者需要后续的药物治疗，包括额外的放射或化疗治疗，以防止癌症复发和残留癌细胞引起的转移。我们的系统将在单细胞水平上实时发现并摧毁残留的癌细胞。邻近关键神经或脑组织的肿瘤特别困难，由我们的成像系统引导的激光治疗将允许外科医生以最小的额外工作彻底根除癌细胞，并且对周围组织没有不良影响。我们的新型单细胞成像设备与聚焦激光消融治疗相结合，将对预防二次手术和后续药物治疗产生重大影响，从而显著节省医疗成本并改善患者护理。

This Small Business Innovation Research Phase I project will develop an intraoperative laser ablative device to simultaneously detect and treat residual cancerous cells in the tumor bed after bulk removal of tumors. Currently, the surgeon sends the resected tumor tissue to pathology to determine whether the surgical margins are clear (clean) of cancer cells. If the margins are not clean, the patient must return for a second surgery. We have developed a fluorescent molecular imaging agent and a wide-field-of-view imaging device to detect residual cancer cells with single cell resolution. The surface is illuminated by a laser and the imaging agent causes the cancer cells to fluoresce at a very specific wavelength. In this NSF-sponsored program, we propose to incorporate ablative technology to this imaging system so that the detected residual cancerous cells can be simultaneously detected and eliminated in real-time during the surgery. Specifically, we will incorporate ablation to our laser imaging system, register the pixel location of cancer targets, destroy the targets with the laser, and provide a feedback confirmation.The broader impacts/commercial potential of this project are improvements in patient care and reduction of healthcare costs. Currently, around 50% of breast cancer patients and 35% of sarcoma patients require second tumor de-bulking surgeries because a final pathology report returns days after the initial surgery indicating that residual cancerous cells have been left within the patient. Furthermore, 25% of the final pathology reports do not detect residual cancer cells due to sampling errors fundamentally inherent in the process. Thus, most patients require subsequent medical therapy including additional radiation or chemotherapy treatment to prevent cancer recurrence and metastasis stemming from residual cancer cells. Our system will find and destroy residual cancer cells in real-time at a single cell level. Tumors adjacent to critical nerve or brain tissue are particularly difficult, and a laser therapy, guided by our imaging system, would allow the surgeon to thoroughly eradicate cancer cells with minimal added work and no adverse effect on surrounding tissue. Our novel single cell imaging device combined with focused laser ablative therapy will have a significant impact on preventing second surgeries and subsequent medical therapy, resulting in significant healthcare cost savings and improved patient care.