Molecular guided surgery for enhanced resection of solid tumors

实体瘤强化切除的分子引导手术

• 批准号: 9915904
• 负责人: Jonathan T Elliott
• 金额: $ 24.9万
• 依托单位: DARTMOUTH-HITCHCOCK CLINIC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9915904
• 关键词: Accreditation; Address; American Association of Cancer Research; Area; Behavior; Blood; Blood Volume; Blood specimen; Calibration; Cancer Biology; Cell Line; Clinic; Clinical; Contrast Media; Data; Detection; Development; Devices; Dyes; Educational workshop; Engineering; Epidermal Growth Factor Receptor; Evaluation; Excision; Exhibits; Feedback; Fluorescence; Funding; Glioma; Goals; Horns; Human; Image; Immunohistochemistry; Implant; Injections; Kinetics; Light; Machine Learning; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of brain; Maps; Measurement; Medical Imaging; Medical center; Mentors; Metabolism; Methods; Modeling; Molecular; Molecular Biology; Morphologic artifacts; Norris Cotton Cancer Center; Nude Rats; Oncology; Operative Surgical Procedures; Optics; Permeability; Physiologic pulse; Procedures; Rattus; Research; Research Personnel; Research Project Grants; Role; Shoes; Signal Transduction; Site; Sodium Fluorescein; Solid; Solid Neoplasm; Source; Spatial Distribution; Structure; Surface; Surgeon; Surgical Oncology; System; Techniques; Technology; Testing; Time; Tissues; Tracer; Training; Training Programs; U251; United States National Institutes of Health; Variant; Visual; Work; absorption; base; blind; cancer surgery; career; clinical investigation; clinical translation; design; experience; fluorescence imaging; fluorescence-guided surgery; human model; imaging approach; imaging modality; imaging system; improved; innovation; knowledge base; lens; member; multidisciplinary; neuro-oncology; neuroimaging; neurosurgery; novel; optical imaging; pre-clinical; pre-clinical research; public health relevance; receptor; receptor expression; skills; standard of care; synergism; training opportunity; translational medicine; tumor

 DESCRIPTION (provided by applicant): The goal of this proposal is to facilitate the candidate's transition to a role as a leading academic researcher and multidisciplinary team member developing optical fluorescence-based technology, with the goal of improving extent of tumor resection (EOTR) in brain cancer. In particular, a focus of this proposal is on advancing fluorescence-guided surgery (FGS) within the context of neurosurgical oncology. To this end, the proposal outlines a mentored-training program with a strong clinical emphasis to compliment the candidate's proficiency in medical and optical imaging, placing the candidate within a critical mass of NIH-funded researchers at Dartmouth Hitchcock Medical Center (DHMC). The plan will focus on four complimentary areas: 1) providing a solid understanding of neurosurgical oncology, 2) developing an expertise in cancer molecular biology, 3) leading a pre-clinical investigation of molecular-guided cancer surgery, 4) expanding skills in optical engineering and machine learning, all of which will emphasize the synergy between understanding the clinical problems in neuro-oncology and advancing technology to address these problems. These goals are strongly supported by an experienced mentor team, led by neurosurgery section-chief Dr. Roberts, alongside NIH-funded researchers Profs. Paulsen, Pogue, and Hoopes. Leveraging the extensive opportunities at Dartmouth, the candidate will use K99 funding to devote time to graduate courses in cancer biology, medical imaging, and translational medicine, and to attend cancer workshops, training seminars, and CME-accredited Grand Rounds at the NCI Norris Cotton Cancer Center. The candidate will also attend AACR workshops to further strengthen clinical understanding of neuro-oncology, and provide a venue for presentation and feedback on the research work. The firm knowledge base gained by this training plan will be applied within the context of a pre-clinical research project to develop and evaluate a novel method of FGS- molecular-guided surgery (MGS) by means of intraoperative receptor concentration imaging (iRCI). The project will extend the rapidly growing field of FGS, applying a novel kinetic imaging approach to allow intraoperative evaluation of tumor-associated receptor expression, and to use this to guide surgical resection. Aim (1) will be to develop and test iRCI in a rat model of GBM, evaluating the accuracy of MGS to identify positive tissue and to improve EOTR compared with current FGS methods. Aim (2) will be to advance the current FGS camera systems, incorporating arterial input function measurement, and reducing absorption and scatter-based artifacts due to surface blood at the surgical site. Aim (3) will be to facilitate iRCI integrationinto the surgical workflow through strategic improvements in dye administration and AIF characterization. This proposal will expand the candidate's knowledge-base in cancer biology and surgical oncology, through extensive training opportunities and interactions with a strong multi-disciplinary team of mentors, equipping the candidate with all the necessary skills to accelerate the trajectory of his promising research career.

 描述（由适用提供）：该提案的目的是促进候选人的过渡到发展基于光荧光技术的领先学术研究员和多学科团队成员，以改善脑癌的肿瘤切除范围（EOTR）。特别是，该提案的重点是在神经外科肿瘤学的背景下推进荧光引导手术（FGS）。为此，该提案概述了一项重视临床的修改训练计划，以补充候选人在医学和光学成像方面的熟练程度，将候选人放在关键 达特茅斯希区柯克医学中心（DHMC）的NIH资助的研究人员的群众。 The plan will focus on four complimentary areas: 1) providing a solid understanding of neurosurgical oncology, 2) developing an expertise in cancer molecular biology, 3) leading a pre-clinical investigation of molecular-guided cancer surgery, 4) expanding skills in optical engineering and machine learning, all of which will emphasize the synergy between understanding the clinical problems in Neuro-oncology and advancing technology to address these problems.这些目标得到了由神经外科部门主持罗伯茨博士和NIH资助的研究人员教授领导的经验精神团队的强烈支持。 Paulsen，Pogue和Hoopes。候选人利用在达特茅斯（Dartmouth）的大量机会，将利用K99资金将时间用于癌症生物学，医学成像和翻译医学的研究生课程，并参加NCI Norris Cotton Cotton Cancer Cancer Center Center在NCI NORRIS棉花癌中心参加癌症研讨会，培训半货和CME认可的大轮胎。候选人还将参加AACR研讨会，以进一步加强对神经肿瘤学的临床理解，并为研究工作提供介绍和反馈。该培训计划获得的公司知识基础将在临床前研究项目的背景下应用，以通过术中受体浓度成像（IRCI）来开发和评估一种新型的FGS-分子引导手术（MGS）。该项目将扩展FG的快速生长的领域，采用一种新型的动力学成像方法来允许对肿瘤相关受体表达的术中评估，并使用它来指导手术切除。目的（1）将是在GBM大鼠模型中开发和测试IRCI，评估MGS的准确性以鉴定阳性组织并改善EOTR，并与当前的FGS方法相比。 AIM（2）将是推进当前的FGS摄像头系统，结合动脉输入功能测量，并减少手术部位表面血液引起的滥用和基于散射的伪影。目的（3）将是通过染料给药和AIF表征的战略改进来促进IRCI整合手术工作流程。该建议将通过与强大的多学科导师团队的广泛培训机会以及互动，使候选人拥有所有必要的技能，以加快他承诺研究职业的轨迹，从而扩大候选人在癌症生物学和外科肿瘤学方面的知识基础。