Image-Guided Resection to Improve Outcome for Children with Medulloblastoma

髓母细胞瘤是一种未分化的小脑神经上皮性肿瘤，是最常见的肿瘤。 儿童恶性脑瘤。虽然目前的医疗实践显著提高了存活率 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 造成严重的神经损伤。髓母细胞瘤的治疗标准包括手术切除。 然后是放射治疗和化疗。尽管更大的切除有效地移除了 肿瘤与患者预后的改善相关，外科医生必须尝试将损害降至最低 围绕着健康的脑组织。为了改善肿瘤的可视化和定位，我们的目标是适应双轴 共焦(DAC)显微镜，以检测肿瘤边缘和指导手术切除，并发现新的 可用新型分子探针标记边缘的试剂，可明显区分肿瘤和正常组织 组织。DAC显微镜将改装一个GRIN中继镜，以进入切除的腔内 并询问边缘是否有残留的癌组织。正在开发的成像试剂将 包括多肽和抗体，我们将对其进行提炼，以用作标记小鼠和人类的荧光探针 髓母细胞瘤。这些试剂是基于通过高通量分析获得的数据来选择的 包括DNA微阵列和噬菌体展示，并利用商业上可用的试剂。 这些标记与肿瘤边缘的结合将使用改进的共聚焦显微镜进行可视化，即 基于双轴设计，将对其进行改进，以优化手术切除。我们将发展 利用肿瘤和正常脑的显微解剖特征识别肿瘤边缘的软件 用活性染料染色。对显微镜的修改包括稳定系统和 通过一次性笔尖启用多光谱分析。为了在诊所测试显微镜，我们将首先使用 FDA批准的染料作为造影剂。在我们开发新试剂的同时，我们还将验证它们在 影像引导下的切除。我们还将开发图像处理算法，以帮助区分 来自周围正常脑组织的肿瘤。这里提出的研究将作为使用 分子探针和先进显微镜在精密影像引导下切除脑实质肿瘤中的应用 人类。这个项目的目标的成功完成将对遭受痛苦的儿童产生重大的好处。 通过延长无病生存期和减少相关的神经缺陷来预防髓母细胞瘤 肿瘤切除手术。

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.