Dual-axis Confocal Microscope for Image-guided Resection of Medulloblastoma

描述(由申请人提供)：申请人寻求在生物医学光学技术的发展中建立终身教职的学术生涯，以帮助诊断、治疗和了解人类疾病，特别是癌症。他计划开发先进的光学设备，能够通过有针对性的光学探针对分子功能进行成像，在临床和临床前研究中利用这种技术来改善患者的预后。申请人是斯坦福大学医学院的博士后研究员，他正在那里接受培训 克里斯·康塔格博士是这一不断发展的领域的先驱，他的研究小组将分子成像技术与成像、动物模型、肿瘤生物学和分子医学的最新发展结合在一起。斯坦福大学分子成像项目(MIPS)由Sam Gambhir博士和Chris Contag博士共同指导，是申请者理想的培训场所。这个临床前项目结合了技术开发和生物标记物的发现，用于在切除髓母细胞瘤(MB)期间进行功能成像指导，MB是最常见的儿童脑肿瘤。一种新的成像技术，双轴共聚焦显微镜(DACM)，将被开发用于成像靶向MB生物标记物的荧光肽探针。桌面DACM将与靶向多肽探针一起用于成像MB的自发性小鼠肿瘤模型。将使用定量比率成像方法来提高肿瘤与正常图像的对比度，并通过优化成像深度、探针浓度和漂洗去除未结合探针的程序等参数来最大化这一对比度。将开发一种微型DACM，其中包括一个直径1-2 mm的梯度折射率“针”透镜，以指导小鼠的MB去除手术。通过生物发光成像(BLI)和监测总存活率，可以量化残留肿瘤质量和复发时间，从而改善切除效果。这些技术和方法将使外科医生能够以细胞准确性和分子特异性深入显示肿瘤边缘，从而使大脑中的MB能够更完整和准确地切除。 相关性：该项目将开发一种显微成像工具，以及靶向造影剂，以提高外科医生切除脑瘤的能力。由于肿瘤切除的程度与患者的预后相关，而且需要准确的切除以防止神经损伤，因此对公共健康的潜在影响是深远的。

DESCRIPTION (provided by applicant): The applicant seeks to establish a tenure-track academic career in the development of biomedical optical technologies to aid in the diagnosis, treatment, and understanding of human diseases, and especially cancer. He plans to develop advanced optical devices that are capable of imaging molecular function through targeted optical probes, utilizing such technologies in clinical and preclinical studies to improve patient outcomes. The applicant is a postdoctoral fellow in the Stanford University School of Medicine, where he is being trained in molecular imaging techniques in the research group of Dr. Chris Contag, a pioneer in this growing field that combines the latest developments in imaging, animal models, tumor biology, and molecular medicine. The Molecular Imaging Program at Stanford (MIPS), co-directed by Drs. Sam Gambhir and Chris Contag, is an ideal training ground for the applicant. This preclinical project combines technology development with biomarker discovery for functional image guidance during resection of meduloblastoma (MB), the most common pediatric brain tumor. A novel imaging technology, the dual-axes confocal microscope (DACM), will be developed to image fluorescent peptide probes that target MB biomarkers. A tabletop DACM will be used, along with targeted peptide probes, to image a spontaneous mouse tumor model of MB. A quantitative ratiometric-imaging method will be employed to improve tumor-to-normal image contrast, which will also be maximized by optimizing parameters such as imaging depth, probe concentration, and the procedure for rinse removal of unbound probe. A miniature DACM, which incorporates a 1 - 2 mm diameter gradient index "needle" lens, will be developed to guide MB debulking surgeries in mice. Improved resection will be demonstrated by quantifying residual tumor mass, and time-to-relapse, through bioluminescent imaging (BLI), and by monitoring overall survival. These technologies and methods will enable more complete and accurate resection of MB in the brain by allowing surgeons to deeply visualize tumor margins with cellular accuracy and molecular specificity. RELEVANCE: This project will develop a microscopic imaging tool, along with targeted contrast agents, to improve the ability of surgeons to remove brain tumors. Since the extent of tumor removal correlates with patient outcomes, and accurate resections are desired to prevent neurological damage, the potential impact on public health is far reaching.