Nuclear magnetic resonance spectroscopy (NMR or MRS) plays a unique role in the current national effort towards personalized medicine, enabling the investigation of metabolism in intact, functioning tissues inherently integrated with the power of structural and functional MR imaging. While it is recognized that MRS is a unique/advantageous detection technique for metabolic studies, the universally acknowledged crucial drawback is a lack of sensitivity. Adequate signal and the ability to resolve similar molecules are two factors that are essential for practical, routine use of MRS relevant to patients. Both improve dramatically at high fields, making the recent availability of whole body commercial 7T systems a powerful tool added to the armament of biochemists striving to make MRS a practical (i.e. suitably sensitive) in vivo detection tool. A second technique for increasing the sensitivity of the NMR experiment is through the use of phased array RF coils. Ideally then, phased arrays would be used in combination with the benefits of high field MRS. This endeavor is currently hampered by the fact that commercial 7T scanners are limited in their number of multi-nuclear receiver channels, instead enabling the potentially more immediate interest in multi-channel 1H imaging. This proposal aims to overcome this limitation by developing an 'add-on'frequency converter to provide any system with broadband multi-channel capability equal to the number of available 1H channels and by developing surface and volume array coils for 1H and 13C spectroscopy at 7T. This project will leverage and promote distinctive capabilities in an existing collaboration between the Magnetic Resonance Systems Lab at Texas A&M University and the Advanced Imaging Research Center at UT Southwestern Medical Center. The specific metabolic processes to be investigated are part of ongoing studies at UTSW to understand breast cancer and the factors predisposing breast cancer. This work will develop technology to more sensitively detect choline in breast tumors as an indicator of malignancy and a high risk of aggressive behavior of tumors. Another issue of great interest to the public is the role of diet in the pathogenesis of breast cancer, with the general hypothesis that a diet high in saturated and monounsaturated fats is an environmental determinant of breast cancer. It has proven difficult to study the relation of breast fat composition to the risk of cancer with invasive biopsies, and this work will support the role of 13C NMR spectroscopy as a largely unexplored alternative.
Three specific aims are outlined to accomplish this work: 1) Build an add-on multi-channel frequency shifting interface box to enable the existing 16-channel 1H receiver on the Philips Achieva 7T scanner at UT Southwestern Medical Center to provide broadband multi-channel receive capability 2) Design and construct 16-channel RF coil arrays for surface and volume 1H and 13C NMR studies at 7T and 3) Demonstrate quantification of the lipid profile and soluble metabolites using multi- channel 13C and 1H MR spectroscopy at 7 Tesla.
Realizing the vision of personalized medicine includes exploiting information about a person's genes, proteins, and cellular environment to understand, prevent, diagnose, and treat disease. Nuclear Magnetic Resonance Spectroscopy (MRS) plays a unique role in this effort, enabling the non-invasive investigation of metabolic pathways in intact, functioning tissues with inherently integrated structural and functional information from MR imaging. This work aims to enhance the capability of MRS by increasing the sensitivity of the method with engineering hardware solutions, thus enabling new insights into the processes of disease.
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