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: 10224672
• 负责人: Eric R Henderson
• 金额: $ 16.97万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224672
• 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; 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; porcine model; 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.

项目概要 癌症手术的主要目标是治愈患者的肿瘤之一。 最大的挑战是成功区分癌症组织和非癌症组织。 引导手术从根本上改变了外科医生做出这一决定的能力， 更好的结果；然而，荧光引导目前仅适用于以下肿瘤的情况： 靠近其母体器官的表面，例如喉咙或膀胱，或已切除的癌症 零碎的，例如脑肿瘤，在这两种情况下，肿瘤都是直接通过表面可视化的。 许多癌症，例如我在临床实践中治疗的肉瘤，都是基于荧光指导的。 理想情况下，肿瘤周围有正常组织区域被切除；该区域被称为“肿瘤周围区域”。 这种手术称为广泛局部切除，手术的成功与否取决于手术的成功与否。 通过切除样本的切割表面是否存在癌细胞来确定， 由病理学家审查，病理学家将边缘分类为阳性，其中癌症。 细胞存在于样本表面——广泛的局部切除失败，或者阴性，只有正常的 组织存在于样本表面——基于已发表的成功的广泛局部切除。 据报道，广泛局部切除术失败的概率约为 20-25%，这会对患者产生负面影响 将荧光引导应用于广泛的局部切除手术有望改善患者的预后。 向外科医生提供有关仪器到肿瘤的距离的实时反馈 表面，从而指导外科医生边缘的厚度并帮助避免失败 手术——这种实践上的改变将是革命性的癌症手术。 理论上来说，需要进行广泛的局部切除是可能的，但是，这需要确定癌症的位置； 通过间接的地下荧光引导进行监测，这在当前技术中是不可能的。 我是一名接受过专科培训的肌肉骨骼肿瘤外科医生，这是骨科的一个亚专业，致力于 对骨肉瘤和软组织肉瘤患者进行手术治疗，通常需要根治性、肢体 我相信荧光引导手术具有巨大的治疗前景。 我已经完成了对患有肉瘤和其他需要广泛局部切除的癌症的患者的开创性工作。 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，并了解为了追求我的职业目标，我 通过这个奖项，我将进行指导性的研究和教学。 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医生科学家并实现我的初级目标 职业目标：促进对肉瘤患者有意义和变革性的研究。

项目成果

Dynamic contrast-enhanced fluorescence imaging compared with MR imaging in evaluating bone perfusion during open orthopedic surgery.

动态对比增强荧光成像与磁共振成像在评估开放骨科手术期间骨灌注方面的比较。

• 发表时间: 2022
• 作者: Tang, Yue;Sin, Jessica M;Gitajn, I Leah;Cao, Xu;Han, Xinyue;Elliott, Jonathan T;Yu, Xiaohan;Christian, Melanie L;Bateman, Logan;Chockbengboun, Theresa;Henderson, Eric R;Pogue, Brian W;Jiang, Shudong
• 通讯作者: Jiang, Shudong

ON SURGICAL FAILURES: Onward to objective evaluation of our less proud moments.

关于手术失败：对我们不那么自豪的时刻进行客观评估。

• 发表时间: 2019-02
• 作者: Henderson; Eric R
• 通讯作者: Eric R

Endosteal and periosteal blood flow quantified with dynamic contrast-enhanced fluorescence to guide open orthopaedic surgery.

通过动态对比增强荧光定量骨内膜和骨膜血流量，以指导开放式骨科手术。

• 发表时间: 2020-02
• 作者: Jiang, Shudong;Elliott, Jonathan T;Gunn, Jason R;Xu, Cao;Ruiz, Alberto J;Henderson, Eric R;Pogue, Brian W;Gitajn, I Leah
• 通讯作者: Gitajn, I Leah

Lead Optimization of Nerve-Specific Fluorophores for Image-Guided Nerve Sparing Surgical Procedures.

用于图像引导神经保留手术程序的神经特异性荧光团的先导优化。

• 发表时间: 2021-04
• 作者: Barth, Connor W;Wang, Lei G;Montano, Antonio;Antaris, Alexander L;Klaassen, Alwin;Sorger, Jonathan;Kerr, Darcy A;Henderson, Eric R;Alani, Adam W G;Gibbs, Summer L
• 通讯作者: Gibbs, Summer L

Early identification of life-threatening soft-tissue infection using dynamic fluorescence imaging: first-in-kind clinical study of first-pass kinetics.

使用动态荧光成像早期识别危及生命的软组织感染：首次通过动力学的临床研究。

• 发表时间: 2023
• 作者: Streeter, Samuel S;Ray, Gabrielle S;Bateman, Logan M;Hebert, Kendra A;Bushee, Fallon E;Rodi, Scott W;Gitajn, I Leah;Ahn, Jaimo;Singhal, Sunil;Martin, Niels D;Bernthal, Nicholas M;Lee, Christopher;Obremskey, William T;Schoenecker, Jonathan G
• 通讯作者: Schoenecker, Jonathan G