title: A rapid method for direct detection of metabolic conversion and magnetization exchange with application to hyperpolarized substrates.
abstract: In this work, we present a new MR spectroscopy approach for directly observing nuclear spins that undergo exchange, metabolic conversion, or, generally, any frequency shift during a mixing time. Unlike conventional approaches to observe these processes, such as exchange spectroscopy (EXSY), this rapid approach requires only a single encoding step and thus is readily applicable to hyperpolarized MR in which the magnetization is not replenished after T(1) decay and RF excitations. This method is based on stimulated-echoes and uses phase-sensitive detection in conjunction with precisely chosen echo times in order to separate spins generated during the mixing time from those present prior to mixing. We are calling the method Metabolic Activity Decomposition Stimulated-echo Acquisition Mode or MAD-STEAM. We have validated this approach as well as applied it in vivo to normal mice and a transgenic prostate cancer mouse model for observing pyruvate-lactate conversion, which has been shown to be elevated in numerous tumor types. In this application, it provides an improved measure of cellular metabolism by separating [1-(13)C]-lactate produced in tissue by metabolic conversion from [1-(13)C]-lactate that has flowed into the tissue or is in the blood. Generally, MAD-STEAM can be applied to any system in which spins undergo a frequency shift.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California - San Francisco, 1700 4th St, San Francisco, CA 94158, USA. peder.larson@ucsf.edu
authors.forename: Peder E Z
authors.initials: PE
authors.lastname: Larson
authors.forename: Adam B
authors.initials: AB
authors.lastname: Kerr
authors.forename: Christine Leon
authors.initials: CL
authors.lastname: Swisher
authors.forename: John M
authors.initials: JM
authors.lastname: Pauly
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Vigneron
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000465:Algorithms; D000818:Animals; D004574:Electromagnetic Fields; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008660:Metabolism; D051379:Mice; D008822:Mice, Transgenic; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D011846:Radio Waves; D014018:Tissue Distribution
chemical_list: D009243:NAD; D019344:Lactic Acid; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase