Image-Guided Resection to Improve Outcome for Children with Medulloblastoma

图像引导切除术可改善髓母细胞瘤儿童的预后

• 批准号: 7990876
• 负责人: CHRISTOPHER H CONTAG
• 金额: $ 14.77万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7990876
• 关键词: Address; Algorithms; Amino Acids; Anatomy; Animals; Antibodies; Binding; Brain; Brain Neoplasms; Cell Surface Proteins; Cell surface; Cerebellum; Chemistry; Child; Childhood; Clinic; Clinical; Clinical Research; Complement; Contrast Media; DNA; Data; Detection; Development; Discrimination; Disease; Disease-Free Survival; Dyes; Excision; FDA approved; Fluorescent Dyes; Fluorescent Probes; Foundations; Genes; Goals; Head; Histopathology; Human; Image; Imagery; Imaging Device; Imaging technology; Label; Lead; Life; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Medical; Methods; Microanatomy; Microscope; Microscopic; Microscopy; Modeling; Modification; Molecular; Molecular Probes; Mus; Nervous System Trauma; Neuroepithelial Neoplasms; Neurologic; Normal tissue morphology; Operative Surgical Procedures; Optics; Outcome; Patients; Peptide Phage Display Library; Peptide antibodies; Peptides; Phage Display; Pilot Projects; Proteomics; Publishing; Radiation therapy; Radiochemistry; Reagent; Relapse; Research; Resected; Residual Cancers; Resolution; Resources; Risk; Robotics; Scanning; Solid; Staging; Staining method; Stains; Statistical Data Interpretation; Surgeon; Survival Rate; Survivors; System; Testing; The Sun; Time; Tissue Microarray; Tissues; Topical application; Transcript; Undifferentiated; arm; base; brain tissue; chemotherapy; design; ergonomics; human tissue; image processing; imaging probe; improved; in vivo; indexing; innovation; instrument; intravenous administration; knockout gene; lens; man; medulloblastoma; miniaturize; molecular marker; mouse model; neoplastic cell; novel; optical imaging; pre-clinical; software development; standard of care; tumor

Medulloblastoma is an undifferentiated, neuroepithelial tumor of the cerebellum and the most common malignant brain tumor in children. While the current medical practice has significantly improved survival rates for children with medulloblastoma, approximately one-third of these patients die, and 20% of survivors sustain severe neurological damage. The standard of care for medulloblastoma includes surgical resection followed by radiation therapy and chemotherapy. Although larger resections that effectively remove the tumor correlate with improved patient outcome, the surgeon must attempt to minimize damage to surrounding healthy brain tissue. To improve tumor visualization and localization, we aim to adapt a dual axis confocal (DAC) microscope to detect tumor margins and guide surgical resection, and to identify new reagents that can mark the margins with novel molecular probes for clear differention of tumor from normal tissue. The DAC microscope will be modified with a GRIN relay lens to reach into the cavity ofthe resected tumor and interrogate the margins for residual cancer. The imaging reagents that are being developed will include peptides and antibodies that we will refine for use as fluorescent probes that label mouse and human medulloblastoma. These reagents are selected based on data obtained by high throughput analyses including DNA microarays and phage display, and take advantage of commercially available reagents. Binding of these markers to tumor margins will be visualized using the refined confocal microscope that is based on a dual axis design and will be modified for optimal use for surgical resection. We will develop software to identify tumor margins using the microanatomic features of cancer and normal brain after staining with vital dyes. The modifications to the microscope include those that stabilize the system and enable multispectral analyses through a disposable tip. To test the microscope in the clinic we will first use a FDA-approved dye as a contrast agent. As we develop new reagents, we will also validate their utility in image-guided resections. We will also develop image-processing algorithms to aid in the discrimination of tumors from surrounding normal brain. The research proposed here will serve as a foundation for the use of molecular probes and advanced microscopy for precision image-guided resection of solid brain tumors in humans. Successful completion of the aims to this project will have a significant benfit for children suffering from medulloblastoma by prolonging disease-free survival and reducing the neurological deficits associated with tumor resection.

髓母细胞瘤是一种未分化的，神经上皮肿瘤的小脑和最常见的 儿童恶性脑肿瘤虽然目前的医疗实践大大提高了存活率， 对于患有髓母细胞瘤的儿童，大约三分之一的患者死亡，20%的幸存者 严重的神经损伤髓母细胞瘤的标准治疗包括手术切除 随后进行放射治疗和化疗。虽然更大的切除可以有效地去除 肿瘤与改善患者预后相关，外科医生必须尝试将损伤降至最低， 周围健康的脑组织为了改善肿瘤的可视化和定位，我们的目标是采用双轴 共聚焦（DAC）显微镜检测肿瘤边缘和指导手术切除，并确定新的 用新型分子探针标记肿瘤边缘的试剂， 组织. DAC显微镜将使用GRIN中继透镜进行修改，以进入切除的腔内 检查肿瘤边缘是否有残留癌细胞正在开发的成像试剂将 包括我们将改进用作标记小鼠和人类荧光探针的肽和抗体 髓母细胞瘤这些试剂是根据高通量分析获得的数据选择的 包括DNA微阵列和噬菌体展示，并利用商业上可获得的试剂。 这些标记物与肿瘤边缘的结合将使用改进的共聚焦显微镜来观察， 基于双轴设计，并将进行修改以最佳地用于手术切除。我们将开发 软件，以确定肿瘤边缘使用显微解剖特征的癌症和正常的大脑后， 用活体染料染色。对显微镜的修改包括那些稳定系统的修改， 通过一次性尖端实现多光谱分析。为了在临床上测试显微镜，我们将首先使用 FDA批准的造影剂。当我们开发新试剂时，我们还将验证它们在以下方面的实用性： 图像引导切除术。我们还将开发图像处理算法，以帮助区分 肿瘤周围正常的大脑。这里提出的研究将作为使用 分子探针和先进的显微镜技术用于脑实体瘤的精确图像引导切除 人类该项目目标的成功完成将为遭受痛苦的儿童带来巨大的利益。 通过延长无病生存期和减少相关的神经功能缺损， 肿瘤切除术