Multimodal Fluorescence- and Imaging-Guided Surgical Navigation: Developing Methods for Subsurface, Indirect Visualization of Cancers Requiring Wide Local Excision

项目摘要 癌症手术的主要目的是治愈患者的肿瘤。一位肿瘤外科医生 最大的挑战是成功区分癌组织和非癌组织。荧光- 引导手术已经从根本上改变了外科医生做出这种决定的能力， 更好的结果;然而，荧光引导目前仅适用于 靠近母体器官的表面，如喉咙或膀胱，或被切除的癌症 比如脑肿瘤在这两种情况下，肿瘤都是直接用表面- 基于荧光引导。许多癌症，比如我在临床实践中治疗的肉瘤， 理想的是与肿瘤周围的正常组织区域一起去除;该区域被称为 裕度这种类型的手术被称为广泛的局部切除和手术的成功或失败是 通过在取出的样本的切割表面上癌细胞的存在或不存在来确定， 由病理学家检查。病理学家将边缘分类为阳性，其中癌症 细胞存在于标本的表面-一个失败的广泛的局部切除，或阴性，只有正常的 组织存在于标本的表面-一个成功的广泛的局部切除。基于已发表 据报道，失败的广泛局部切除发生约20-25%的时间，这对 患者结局。将荧光引导应用于广泛的局部切除手术， 为外科医生提供关于从他们的仪器到肿瘤的距离的实时反馈， 表面，从而指导外科医生关于边缘的厚度，并帮助避免失败。 手术--这样的改变在实践中将是革命性的。癌症的放射性引导手术 在理论上，需要广泛的局部切除是可能的;然而，这将需要癌症的位置， 通过间接的地下荧光引导进行监测，这在当前技术下是不可能的。我 我是一名受过奖学金培训的肌肉骨骼肿瘤外科医生，这是骨科的一个分支，致力于 骨和软组织肉瘤患者的手术治疗通常需要根治性，肢体， 节省操作。我相信荧光引导手术对于治疗 需要广泛局部切除的肉瘤和其他癌症患者。我完成了一项开创性的工作 然而，为了解决必须填补的知识空白，以便将这一概念转化为实践，我 我认识到我的知识和技能的局限性，并明白为了追求我的职业目标， 需要额外的培训。通过这个奖项，我将追求指导研究和教学法， 生物医学光学，先进的成像技术和临床研究设计，使我能够 从初级临床研究员转变为独立的临床科学家，并实现我的主要目标 职业目标：促进对肉瘤患者有意义和变革性的研究。

Project Summary The primary goal of cancer surgery is to cure patients of their tumors. One of the oncological surgeon’s greatest challenges is to successfully distinguish cancer tissue from non-cancer tissue. Fluorescence- guided surgery has radically changed the surgeon’s ability to make this determination, with demonstrably better outcomes; however, fluorescence guidance is currently only applicable in the setting of tumors that are near their parent organ’s surface, such as the throat or bladder, or cancers that are removed piecemeal, such as brain tumors. In both of these scenarios, the tumor is visualized directly with surface- based fluorescence guidance. Many cancers, such as the sarcomas that I treat in clinical practice, are removed ideally with a zone of normal tissue surrounding the tumor; this zone is referred to as the margin. This type of surgery is called a wide local excision and the success or failure of the surgery is determined by the presence or absence of cancer cells at the cut surface of the removed specimen, which is reviewed by a pathologist. The pathologist will classify the margin as positive, where cancer cells are present at the specimen’s surface—a failed wide local excision, or negative, where only normal tissue is present at the specimen’s surface—a successful wide local excision. Based on published reports, failed wide local excisions occur about 20-25% of the time, which have negative effects on patient outcomes. Applying fluorescence guidance to wide local excision surgeries holds the promise of providing real-time feedback to surgeons regarding the distance from their instruments to the tumor’s surface, thereby instructing the surgeon as to the thickness of the margin and helping avoid a failed surgery—such a change in practice would be revolutionary. Fluorescence-guided surgery for cancers requiring wide local excision is possible in theory; however, it would require that the cancer’s location be monitored via indirect, subsurface fluorescence guidance, which is not possible with current technology. I am a fellowship-trained musculoskeletal oncology surgeon, a subspecialty of orthopaedics dedicated to the surgical treatment of patients with bone and soft-tissue sarcomas that generally require radical, limb- sparing operations. I believe that fluorescence-guided surgery holds tremendous promise for treating patients with sarcomas and other cancers requiring wide local excision. I have completed seminal work to address knowledge gaps that must be filled in order to translate this concept into practice, however, I realize the limits of my knowledge and skills and understand that in order to pursue my career goals I require additional training. Through this award I will pursue mentored research and didactics in biomedical optics, advanced imaging technology, and clinical research design that will enable me to transition from a junior clinical researcher into an independent clinician-scientist and achieve my primary career goal: to facilitate meaningful and transformative research for patients with sarcoma.