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

多模态荧光和成像引导手术导航：开发需要广泛局部切除的癌症的地下、间接可视化方法

• 批准号: 9975158
• 负责人: Eric R Henderson
• 金额: $ 16.96万
• 依托单位: DARTMOUTH-HITCHCOCK CLINIC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9975158
• 关键词: Address; Affect; Anatomy; Award; Binding; Bladder; Bone Tissue; Brain; Brain Neoplasms; Clinical; Clinical Research; Computer Models; Connective Tissue; Curative Surgery; Data; Dissection; Doxorubicin; Enhancement Technology; Epidermal Growth Factor Receptor; Excision; External Beam Radiation Therapy; Failure; Family suidae; Fatty acid glycerol esters; Feedback; Fellowship; Fluorescence; Goals; Grant; Histologic; Human; Image; Imaging technology; K-Series Research Career Programs; Knowledge; Label; Light; Limb structure; Location; Magnetic Resonance Imaging; Malignant Bone Neoplasm; Malignant Neoplasms; Measurable; Medicine; Mentors; Methods; Modeling; Monitor; Multimodal Imaging; Musculoskeletal; Musculoskeletal System; Neoadjuvant Therapy; Normal tissue morphology; Oncology; Operating Rooms; Operative Surgical Procedures; Optics; Organ; Orthopedics; Outcome; Parents; Pathologist; Patient-Focused Outcomes; Patients; Penetration; Pharyngeal structure; Phase; Property; Publishing; Radiology Specialty; Reporting; Reproducibility; Research; Research Design; Research Personnel; Research Project Grants; Resources; Rodent; Role; Scientist; Seminal; Soft tissue sarcoma; Solid; Specimen; Surface; Surgeon; Surgical Oncologist; Surgical margins; Tactile; Technology; Testing; Thick; Time; Tissues; Training; Translating; Visual; Visualization; Work; base; cancer cell; cancer recurrence; cancer site; cancer surgery; career; chemotherapy; clinical practice; early phase clinical trial; first-in-human; fluorescence imaging; fluorescence-guided surgery; image guided; improved; in vivo; innovation; instrument; malignant muscle neoplasm; malignant oropharynx neoplasm; multimodality; operation; phase I trial; programs; radiological imaging; receptor expression; sarcoma; skills; success; theories; tissue phantom; tumor; uptake; urinary

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.

项目摘要 癌症外科的首要目标是治愈患者的肿瘤。其中一位肿瘤外科医生 最大的挑战是成功区分癌症组织和非癌症组织。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，显然 更好的结果；然而，荧光引导目前仅适用于 靠近其母器官的表面，如喉咙或膀胱癌，或被切除的癌症 零星的，如脑瘤。在这两种情况下，肿瘤都是通过表面直接可视化的- 基于荧光的制导。许多癌症，比如我在临床上治疗的肉瘤，都是 理想情况下，切除肿瘤周围的正常组织区域；这个区域称为 保证金。这种手术被称为局部广泛切除，手术的成败取决于 由移除的样本的切面上是否存在癌细胞来确定， 这是由病理学家审查的。病理学家会将边缘归类为阳性，即癌症 细胞存在于标本表面--失败的广泛局部切除，或阴性，只有正常的 组织出现在标本的表面--成功地进行了广泛的局部切除。基于已发布的 据报道，失败的局部切除手术失败的几率约为20%-25%，对 病人的结果。将荧光引导应用于广泛的局部切除手术有望 向外科医生提供有关器械到肿瘤的距离的实时反馈 表面，从而指示外科医生关于边缘的厚度并帮助避免失败 外科手术--这种做法的改变将是革命性的。荧光引导下的肿瘤外科手术 从理论上讲，要求广泛的局部切除是可能的；然而，这将要求癌症的位置 通过间接的地下荧光引导进行监测，这在目前的技术中是不可能的。我 我是一名接受过团契培训的肌肉骨骼肿瘤学外科医生，是骨科的一个子专业，致力于 骨和软组织肉瘤患者的外科治疗通常需要根治，四肢- 备用操作。我相信荧光引导手术在治疗方面有着巨大的希望。 肉瘤和其他癌症患者需要广泛的局部切除。我已经完成了开创性的工作 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 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，我 需要额外的培训。通过这个奖项，我将继续进行指导研究和教学在 生物医学光学，先进的成像技术和临床研究设计，使我能够 从初级临床研究人员过渡到独立的临床科学家并取得我的初步成就 职业目标：促进肉瘤患者有意义和变革性的研究。