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Rapid, [Formula: see text] ‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux

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...

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Autores principales: Miller, Jack J., Valkovič, Ladislav, Kerr, Matthew, Timm, Kerstin N., Watson, William D., Lau, Justin Y. C., Tyler, Andrew, Rodgers, Christopher, Bottomley, Paul A., Heather, Lisa C., Tyler, Damian J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986077/
https://www.ncbi.nlm.nih.gov/pubmed/33538063
http://dx.doi.org/10.1002/mrm.28647
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author Miller, Jack J.
Valkovič, Ladislav
Kerr, Matthew
Timm, Kerstin N.
Watson, William D.
Lau, Justin Y. C.
Tyler, Andrew
Rodgers, Christopher
Bottomley, Paul A.
Heather, Lisa C.
Tyler, Damian J.
author_facet Miller, Jack J.
Valkovič, Ladislav
Kerr, Matthew
Timm, Kerstin N.
Watson, William D.
Lau, Justin Y. C.
Tyler, Andrew
Rodgers, Christopher
Bottomley, Paul A.
Heather, Lisa C.
Tyler, Damian J.
author_sort Miller, Jack J.
collection PubMed
description 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: see text]) 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: see text] 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: see text] , producing equivalent saturation with a 53% reduction in delivered pulse power and a 33‐fold reduction in spillover at the minimum effective [Formula: see text]. 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 P(i)‐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.
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spelling pubmed-79860772021-03-25 Rapid, [Formula: see text] ‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux Miller, Jack J. Valkovič, Ladislav Kerr, Matthew Timm, Kerstin N. Watson, William D. Lau, Justin Y. C. Tyler, Andrew Rodgers, Christopher Bottomley, Paul A. Heather, Lisa C. Tyler, Damian J. Magn Reson Med Full Papers—Spectroscopic Methodology 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: see text]) 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: see text] 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: see text] , producing equivalent saturation with a 53% reduction in delivered pulse power and a 33‐fold reduction in spillover at the minimum effective [Formula: see text]. 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 P(i)‐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. John Wiley and Sons Inc. 2021-02-03 2021-06 /pmc/articles/PMC7986077/ /pubmed/33538063 http://dx.doi.org/10.1002/mrm.28647 Text en © 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers—Spectroscopic Methodology
Miller, Jack J.
Valkovič, Ladislav
Kerr, Matthew
Timm, Kerstin N.
Watson, William D.
Lau, Justin Y. C.
Tyler, Andrew
Rodgers, Christopher
Bottomley, Paul A.
Heather, Lisa C.
Tyler, Damian J.
Rapid, [Formula: see text] ‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux
title Rapid, [Formula: see text] ‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux
title_full Rapid, [Formula: see text] ‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux
title_fullStr Rapid, [Formula: see text] ‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux
title_full_unstemmed Rapid, [Formula: see text] ‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux
title_short Rapid, [Formula: see text] ‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux
title_sort rapid, [formula: see text] ‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial atp flux
topic Full Papers—Spectroscopic Methodology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986077/
https://www.ncbi.nlm.nih.gov/pubmed/33538063
http://dx.doi.org/10.1002/mrm.28647
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