Research using Xenopus (frog) embryos, a model system of major importance in many areas of biomedicine, is hampered in a fundamental way by their opacity. No device for non-destructively imaging the interiors of these specimens is generally available. The long-term goal at ABQMR, Inc. is to utilize unique capabilities in the field of miniaturized NMR and MRI instrumentation to develop new devices to overcome such problems in biomedical research and other fields. The objective for this application is a mature Ultra- Compact MRI (UC-MRI) prototype, ready for deployment in research labs, optimized in size, cost, and complexity to match the constraints of Xenopus embryology research. Preliminary experiments on phantoms, oocytes, and fixed embryos show that images at the necessary spatial and temporal resolutions are within reach of the current generation of miniaturized hardware. The central hypothesis driving this effort is that a fully miniaturized UC-MRI device can be constructed and operated in the biology research laboratory to produce images of live embryos of sufficient quality to answer important questions in Xenopus research. The rationale for this work is that the availability of a Xenopus-optimized UC-MRI device will dramatically increase the access to non-destructive MRI technology, improving data quality and enabling new types of research experiments utilizing Xenopus in a wide range of biomedical fields. The project has three staged specific aims. First, build a next generation UC-MRI prototype that meets the needs of Xenopus embryology research. Preliminary work indicates the required basic improvements: increased magnetic field gradient strength, lower temperature operation at 15: C and enhanced tissue contrast via selective fatty tissue excitation. Second, demonstrate that the UC-MRI can acquire research-quality Xenopus embryo images. Working in the R&D lab with slow growing late-stage embryos, the operating protocol of the Xenopus-optimized UC-MRI will be adjusted to provide images of sufficient quality to allow reproduction of published research analyses. Third, demonstrate the acquisition of research-quality images in a research setting. Images of fast growing early- stage embryos will be acquired by developmental biologists in their own lab. Given that existing prototypes are very small, rugged, and of modest cost, the accomplishment of these aims will show that this new, technically innovative miniaturization of MRI technology is fully capable of research-quality imaging in the hands of typical researchers. The ultimate product, a highly miniaturized UC-MRI device optimized in all respects for use in Developmental Biology, is significant because it establishes universal access to MRI instrumentation, instrumentation that overcomes the essential limitation imposed by opacity, yielding new and better data in Xenopus embryo research, and positively impacting many of the biomedical research areas funded by the NIH.
The proposed research is relevant to public health because it develops an important, currently missing tool for Xenopus embryology research, non-destructive imaging, which will further enhance the utility of this organism for addressing the fundamental biology of human disease. The project is relevant to the mission of the NCRR because it will establish a new resource for research, the Ultra-Compact MRI, which will allow scientists to advance their understanding of a wide range of diseases.