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

该临床前项目将成像技术开发与生物标志物发现相结合， 在髓母细胞瘤（MB）（最常见的小儿脑肿瘤）切除术中的图像引导。一种新型 成像技术，双轴共焦（DAC）显微镜，将开发图像荧光探针 靶向MB生物标志物。首先，将使用桌面DAC，沿着靶向探头，对 MB自发性小鼠肿瘤模型。将采用定量比率成像方法， 提高肿瘤与正常图像对比度，这也将通过优化参数来最大化， 成像深度、探针浓度和冲洗去除未结合探针的程序。一个微型 DAC，其中包括一个2毫米直径的梯度指数“针”透镜，将开发引导MB 在老鼠身上进行减瘤手术。通过定量残留肿瘤块来证明切除改善， 复发时间和监测总生存期。这些技术和方法将使更多 完整和准确切除脑中的MB，从而通过允许 外科医生可以用细胞准确性和分子特异性来可视化肿瘤边缘。

This preclinical project combines imaging 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-axis confocal (DAC) microscope, will be developed to image fluorescent probes that target MB biomarkers. First, a tabletop DAC will be used, along with targeted 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 DAC, which incorporates a 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, time-to-relapse, and by monitoring overall survival. These technologies and methods will enable more complete and accurate resection of MB in the brain, and will thereby improve patient outcomes, by allowing surgeons to visualize tumor margins with cellular accuracy and molecular specificity.