@article{1af78f03cf5043bc84c103ff90c27884,
title = "Rapid, B1-insensitive, dual-band quasi-adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux",
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.",
keywords = "31P-MRS, ATP, CK-flux reaction, CMR, PCr, RF design, cardiac metabolism, heart, metabolism, pulse design, saturation transfer",
author = "Miller, {Jack J.} and Ladislav Valkovi{\v c} and Matthew Kerr and Timm, {Kerstin N.} and Watson, {William D.} and Lau, {Justin Y.C.} and Andrew Tyler and Christopher Rodgers and Bottomley, {Paul A.} and Heather, {Lisa C.} and Tyler, {Damian J.}",
note = "Funding Information: All authors thank the British Heart Foundation for their generous support (refs RG/11/9/28921, FS/14/17/30634, FS/17/58/33072, and FS/15/68/32042), the University of Oxford British Heart Foundation Centre for Research Excellence (RE/13/1/30181), and the NHS National Institute for Health Research Oxford Biomedical Research Centre program. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. JJM acknowledges the Postdoctoral Fellowship run in collaboration with Novo Nordisk and the University of Oxford, and thank financial support provided by St Hugh{\textquoteright}s College and Wadham College in the University of Oxford. LV and CTR are funded by a Sir Henry Dale Fellowship from the Royal Society and the Wellcome Trust (098436/Z/12/B). LV also acknowledges the support of Slovak grant agencies VEGA (2/0003/20) and APVV (19-0032). JYCL acknowledges funding from the NIHR Oxford Biomedical Research Centre and support from the Fulford Junior Research Fellowship at Somerville College. AT acknowledges funding from the Engineering and Physical Sciences Research Council (EPSRC) and Medical Research Council (MRC) [grant number EP/L016052/1]. PAB was supported by a Newton Abraham Visiting professorship at Oxford. Funding Information: All authors thank the British Heart Foundation for their generous support (refs RG/11/9/28921, FS/14/17/30634, FS/17/58/33072, and FS/15/68/32042), the University of Oxford British Heart Foundation Centre for Research Excellence (RE/13/1/30181), and the NHS National Institute for Health Research Oxford Biomedical Research Centre program. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. JJM acknowledges the Postdoctoral Fellowship run in collaboration with Novo Nordisk and the University of Oxford, and thank financial support provided by St Hugh{\textquoteright}s College and Wadham College in the University of Oxford. LV and CTR are funded by a Sir Henry Dale Fellowship from the Royal Society and the Wellcome Trust (098436/Z/12/B). LV also acknowledges the support of Slovak grant agencies VEGA (2/0003/20) and APVV (19‐0032). JYCL acknowledges funding from the NIHR Oxford Biomedical Research Centre and support from the Fulford Junior Research Fellowship at Somerville College. AT acknowledges funding from the Engineering and Physical Sciences Research Council (EPSRC) and Medical Research Council (MRC) [grant number EP/L016052/1]. PAB was supported by a Newton Abraham Visiting professorship at Oxford. Publisher Copyright: {\textcopyright} 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine",
year = "2021",
month = jun,
doi = "10.1002/mrm.28647",
language = "English (US)",
volume = "85",
pages = "2978--2991",
journal = "Magnetic resonance in medicine",
issn = "0740-3194",
publisher = "John Wiley and Sons Inc.",
number = "6",
}