High Throughput MR Microscopy for Cancer Screening

描述（由申请人提供）：该项目将开发所需的技术，使磁共振组织学（MRH）广泛应用于癌症研究人员，病理学家和分子生物学家，作为一种经济高效的高通量服务。利用本提案中开发的技术，研究人员将能够通过快递将他们的活体动物送到MRPath，在那里动物将使用最近开发的染色方法进行灌注/浸泡固定，该方法将组织信号增加10倍。3D磁共振成像研究将以低至25微米的空间分辨率执行，比临床领域的常规分辨率高6万倍以上，并将生成的图像自动传输到研究人员的计算机上。目标应用包括整个小鼠，小鼠胎儿和小鼠大脑的形态表型。该项目的第一阶段将展示高通量扫描所需的原理证明。更具体地说，我们将开发硬件和软件，使扫描效率比现有方法提高至少200%。这一原理证明将为该项目的第二阶段奠定基础，该阶段将使该方法进入常规使用，并在三个目标市场（癌症模型的全鼠筛选；小鼠胎儿的结构表型；小鼠的神经毒理学）中验证MRH的价值。在第二阶段，这些演示将在一天内实现多达100个3D图像集的完全自动化采集。我们将针对三个非常不同的应用：全鼠肿瘤总质量筛选；全鼠胚胎/胎儿发育生物学筛选小鼠和大鼠脑筛选的神经毒理学和神经生物学。

DESCRIPTION (provided by applicant): This project will develop the technologies required to make magnetic resonance histology (MRH) broadly available as a cost effective high throughput service to cancer researchers, pathologists and molecular biologists. With the technology developed in this proposal investigators will be able send their live animals via courier to MRPath where the animals will be perfusion/immersion fixed using recently developed staining methods that increase the tissue signal by 10X. 3D MR imaging studies will be executed at spatial resolution down to 25 microns, more than 60,000X higher resolution than is routine in the clinical arena with resulting imagery delivered automatically to the investigator's computer. Target applications include morphologic phenotyping of whole mice, mouse fetuses and mouse brains. Phase I of the project will demonstrate proof of principles required for high throughput scanning. More specifically we will develop the hardware and software to increase the scan efficiency by at least 200% over existing methods. This proof of principle will lay the groundwork for phase II of the project which will move the method to routine use and validate the value of MRH in three targeted markets (whole mouse screening in cancer models; structural phenotyping in the mouse fetus; neurotoxicology in the mouse). These demonstrations will enable, in Phase II, totally automated acquisition of up to 100 3D image sets in a single day. We will target three very diverse applications: whole mouse screening for total tumor mass; whole mouse embryo/fetus screening for developmental biology; mouse and rat brain screening for neurotoxicology and neurobiology.