Dynamic UltraFast 2D EXchange SpectroscopY (UF-EXSY) of hyperpolarized substrates

J Magn Reson. 2015 Aug:257:102-9. doi: 10.1016/j.jmr.2015.05.011. Epub 2015 Jun 15.

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.

Keywords: (13)C; 2D NMR; Chemical exchange; EXSY; Hyperpolarized; MCT4; Stimulated echo; Ultrafast.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alanine / analysis
  • Carcinoma, Renal Cell / chemistry
  • Cell Line, Tumor
  • Enzyme Inhibitors / pharmacology
  • Enzymes / chemistry
  • Humans
  • Kidney Neoplasms / chemistry
  • L-Lactate Dehydrogenase / analysis
  • Lactic Acid / analysis
  • Monocarboxylic Acid Transporters / antagonists & inhibitors
  • Monocarboxylic Acid Transporters / chemistry
  • Muscle Proteins / antagonists & inhibitors
  • Muscle Proteins / chemistry
  • Nuclear Magnetic Resonance, Biomolecular / instrumentation
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Pyruvic Acid / analysis
  • Reproducibility of Results
  • Urea / chemistry

Substances

  • Enzyme Inhibitors
  • Enzymes
  • Monocarboxylic Acid Transporters
  • Muscle Proteins
  • SLC16A4 protein, human
  • Lactic Acid
  • Pyruvic Acid
  • Urea
  • L-Lactate Dehydrogenase
  • Alanine