This proposal is being submitted in response to Notice Number (NOT-OD-09-058) and Notice Title: NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications. This proposed revision to parent grant, """"""""Technique Development for Hyperpolarized C13 MR Studies"""""""" has been designed to fulfill the ARRA goals of """"""""job creation and retention"""""""" and will """"""""accelerate the tempo of scientific research"""""""" through a significant expansion of the scope and research of the parent grant. While the parent grant is focused on the development of specialized hyperpolarized imaging techniques and rf coils for animal (rat &mice) studies, this new revision project aims to develop new methods and coils for future human applications. This represents a key step in the translation of this powerful new metabolic imaging technique from animal studies into a future clinical radiological method. Recent in vivo MR studies of injected 13C-enriched hyperpolarized substrates have demonstrated >50,000- fold 13C signal enhancement and the ability to not only observe uptake but also metabolism in vivo. Through recent studies supported by the parent grant, we have developed and applied new high speed, 3D volumetric and time-resolved hyperpolarized MR techniques at high spatial resolution and high SNR. The techniques and coils developed through the parent project have produced outstanding results in rat and mouse animal models, but are not directly applicable for human studies. Through this revision project, we aim to develop new rf pulses, MR pulse sequences and MR coils for future human studies. In this revision, new human size coils will be designed and constructed. Also new rf pulses will need to be developed for the lower B1 limitations inherent in the human sized coils as compared to the small murine coils developed through the parent grant. Improved MR sequences will be developed including accelerated compressed sensing and parallel imaging techniques to provide the higher spatial coverage rapidly as required for human studies. These developments are critical for the translation of these hyperpolarized techniques for future clinical applications. The proposed project would fund two new full-time positions for post-doctoral researchers at UCSF and at Stanford University (through the subcontract). This revision proposal also will provide the funding for retaining the position of an MR engineer dedicated to this project. This revision will support the addition of new expertise to the project by supporting the effort of a radiologist with extensive experience in clinical and research studies, who will help guide the development of techniques and coils for human studies. This revision project would greatly accelerate the tempo of this research since this important area of translational research could start as soon as funded.
The successful outcome of the proposed revision project will result in the expansion and revision of the parent grant to create new methods and MR coils for future human studies of this exciting new metabolic imaging method. This research effort aims to develop new MR acquisition methods in order to translate techniques used in preclinical animal studies into future radiological tools for human applications.
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