Rapid, B1-insensitive, dual-band quasi-adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux

Jack J. Miller, Ladislav Valkovič, Matthew Kerr, Kerstin N. Timm, William D. Watson, Justin Y.C. Lau, Andrew Tyler, Christopher Rodgers, Paul A. Bottomley, Lisa C. Heather, Damian J. Tyler

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Phosphorus saturation-transfer experiments can quantify metabolic fluxes noninvasively. Typically, the forward flux through the creatine kinase reaction is investigated by observing the decrease in phosphocreatine (PCr) after saturation of γ-ATP. The quantification of total ATP utilization is currently underexplored, as it requires simultaneous saturation of inorganic phosphate ((Formula presented.)) and PCr. This is challenging, as currently available saturation pulses reduce the already-low γ-ATP signal present. Methods: Using a hybrid optimal-control and Shinnar-Le Roux method, a quasi-adiabatic RF pulse was designed for the dual saturation of PCr and (Formula presented.) to enable determination of total ATP utilization. The pulses were evaluated in Bloch equation simulations, compared with a conventional hard-cosine DANTE saturation sequence, before being applied to perfused rat hearts at 11.7 T. Results: The quasi-adiabatic pulse was insensitive to a >2.5-fold variation in (Formula presented.), producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective (Formula presented.). This enabled the complete quantification of the synthesis and degradation fluxes for ATP in 30-45 minutes in the perfused rat heart. While the net synthesis flux (4.24 ± 0.8 mM/s, SEM) was not significantly different from degradation flux (6.88 ± 2 mM/s, P =.06) and both measures are consistent with prior work, nonlinear error analysis highlights uncertainties in the Pi-to-ATP measurement that may explain a trend suggesting a possible imbalance. Conclusions: This work demonstrates a novel quasi-adiabatic dual-saturation RF pulse with significantly improved performance that can be used to measure ATP turnover in the heart in vivo.

Original languageEnglish (US)
Pages (from-to)2978-2991
Number of pages14
JournalMagnetic resonance in medicine
Volume85
Issue number6
DOIs
StatePublished - Jun 2021

Keywords

  • 31P-MRS
  • ATP
  • CK-flux reaction
  • CMR
  • PCr
  • RF design
  • cardiac metabolism
  • heart
  • metabolism
  • pulse design
  • saturation transfer

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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