title: Dynamic UltraFast 2D EXchange SpectroscopY (UF-EXSY) of hyperpolarized substrates.
abstract: In this work, we present a new ultrafast method for acquiring dynamic 2D EXchange SpectroscopY (EXSY) within a single acquisition. This technique reconstructs two-dimensional EXSY spectra from one-dimensional spectra based on the phase accrual during echo times. The Ultrafast-EXSY acquisition overcomes long acquisition times typically needed to acquire 2D NMR data by utilizing sparsity and phase dependence to dramatically undersample in the indirect time dimension. This allows for the acquisition of the 2D spectrum within a single shot. We have validated this method in simulations and hyperpolarized enzyme assay experiments separating the dehydration of pyruvate and lactate-to-pyruvate conversion. In a renal cell carcinoma cell (RCC) line, bidirectional exchange was observed. This new technique revealed decreased conversion of lactate-to-pyruvate with high expression of monocarboxylate transporter 4 (MCT4), known to correlate with aggressive cancer phenotypes. We also showed feasibility of this technique in vivo in a RCC model where bidirectional exchange was observed for pyruvate-lactate, pyruvate-alanine, and pyruvate-hydrate and were resolved in time. Broadly, the technique is well suited to investigate the dynamics of multiple exchange pathways and applicable to hyperpolarized substrates where chemical exchange has shown great promise across a range of disciplines.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Leon Swisher
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, United States.
authors.forename: Bertram
authors.initials: B
authors.lastname: Koelsch
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States.
authors.forename: Subramianam
authors.initials: S
authors.lastname: Sukumar
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States.
authors.forename: Renuka
authors.initials: R
authors.lastname: Sriram
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States.
authors.forename: Romelyn Delos
authors.initials: RD
authors.lastname: Santos
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States.
authors.forename: Zhen Jane
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, United States.
authors.forename: John
authors.initials: J
authors.lastname: Kurhanewicz
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, United States. Electronic address: Dan.Vigneron@ucsf.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vigneron
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, United States. Electronic address: Peder.Larson@ucsf.edu.
authors.forename: Peder
authors.initials: P
authors.lastname: Larson
mesh_terms: D000409:Alanine / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000737:chemistry; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004798:Enzymes / Q000737:chemistry; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D019344:Lactic Acid / Q000032:analysis; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000737:chemistry; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000295:instrumentation / Q000379:methods*; D019289:Pyruvic Acid / Q000032:analysis; D015203:Reproducibility of Results; D014508:Urea / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D004798:Enzymes; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; C406962:SLC16A4 protein, human; D019344:Lactic Acid; D019289:Pyruvic Acid; D014508:Urea; D007770:L-Lactate Dehydrogenase; D000409:Alanine
keywords: (13)C; 2D NMR; Chemical exchange; EXSY; Hyperpolarized; MCT4; Stimulated echo; Ultrafast