The goal of this application is to obtain support for purchase of a 9.4T 20 cm bore horizontal NMR system for in vivo biomedical applications, focused on cancer research. There are 15 major users with 26 peer reviewed grants who will use the 7T and proposed 9.4T systems. There are a wide range of approaches to addressing different oncologic problems, including cancer detection, predicting tumor response, and developing methods of monitoring tumor and drug metabolism to enhance therapeutic outcomes. The projects are highly translational in that most of these methods can be translated to the clinic, based on the relatively common availability of 3T MRI systems, and the growing (although still limited) availability of human magnets at even higher field strengths. One can summarize the long range goal of these collectively diverse projects as the improvement of cancer care by enhancing responses without correspondingly increased toxicity, either by improving therapies or by development of early markers of response (or resistance) so as to avoid side effects from ineffective treatments. The design and methods of the different projects are diverse but common principles will maximize the data obtained from experiments on the proposed system. These methods include 1) continuing high throughput, relatively straightforward animal imaging research needed by numerous investigators on the existing 4.7T system which has a lower field strength but wide bore and can more readily accommodate multiple animals concurrently, 2) focus more demanding experiments on the 7T and proposed 9.4T systems, 3) where necessary, perform appropriate phantom and preliminary experiments to determine which NIH supported users' experiments will gain relatively more by use of the 9.4T vs the 7T system, 4) the use of statistically valid experimental groups and 5) continue our policy of trying to provide support to the various users in the design of experiments, construction of appropriate hardware, and if necessary, assisting in the performance of the experiments to ensure that they are performed in an optimized manner, with best signal to noise possible. The applications that will be supported on the proposed 9.4T instrument address a wide range of oncology problems, as reflected by the different funding mechanisms from which they arise. These include a focus on a wide spectrum of tumors (brain, prostate, breast, sarcomas, colon cancers), addressing varying relevant physiological problems in oncology (hypoxia (lack of oxygen), elevated tumor interstitial pressure leading to poor blood flow and drug delivery, the need for better tumor model systems, improvements in imaging etc). The approaches to addressing these problems are quite varied but have in common the feasibility to readily translate any of these findings from the preclinical to the clinical realm, based on existing technology. ? ? ?
