This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Proton exchange imaging is important as it allows for visualization and quantification of the distribution of specific metabolites with conventional MRI. Current exchange mediated MRI methods suffer from poor contrast as well as confounding factors that influence exchange rates. Chemical Exchange Saturation Transfer (CEST) has become the most popular mechanism to indirectly detect solute content and exchange-related properties. CEST contrast requires that a discrete chemical shift difference between water and the exchangeable proton on the CEST agent is preserved, and is thus most sensitive to the slow to intermediate exchange rate domain (ksw d ??). While CEST is most sensitive to slow proton exchange, spin-lattice relaxation time in the rotating frame (T1?) is another technique that depends on chemical exchange which is more sensitive to faster exchange processes but is not specific to one chemical exchange site. In this study, we are developing a method that combines the sensitivities of CEST MRI to slow exchange processes with the sensitivity of T1? MRI to fast exchange processes (CESTrho). The resulting acquired water signal, referred to as the CESTrho signal, will be specific to the spin-lattice relaxation effects of the CEST saturation pulse as well as the chemical exchange dependent transverse relaxation effects of the T1p pulse. We hypothesize that this sequence should show increased sensitivity along a large spectrum of exchange rates. Further, the CESTrho signal varies linearly with solute concentration and can be used to quantify proton concentration. Finally, we believe that this new sequence can be customized to be insensitive to changes in exchange rate for a large range of exchange rates.
Study Aims : 1. To develop a method to that combines CEST and spin locking techniques that can be used to create image contrast and quantify metabolites with exchangeable protons. 2. To determine the dependence of this new sequence on proton concentration, as well as to devise a magnetization preparation scheme to make it insensitive to changes in chemical exchange. 3. To test this new sequence in vivo in animals to detect changes in metabolite concentrations
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