Rapid, $B_1$-insensitive, dual-band quasi-adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux

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Main Authors: Miller, Jack J., Valkovič, Ladislav, Kerr, Matthew, Timm, Kerstin N., Watson, William, Lau, Justin Y. C., Tyler, Andrew, Rodgers, Christopher, Bottomley, Paul A., Heather, Lisa C., Tyler, Damian J.
Format: Preprint
Published: 2020
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author Miller, Jack J.
Valkovič, Ladislav
Kerr, Matthew
Timm, Kerstin N.
Watson, William
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
Lau, Justin Y. C.
Tyler, Andrew
Rodgers, Christopher
Bottomley, Paul A.
Heather, Lisa C.
Tyler, Damian J.
contents Purpose: Phosphorus saturation-transfer experiments can quantify metabolic fluxes non-invasively. 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 utilisation is currently under-explored, as it requires simultaneous saturation of inorganic phosphate (Pi) 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 Pi to enable determination of total ATP utilisation. The pulses were evaluated in Bloch equation simulations, compared with a conventional hard-cosine DANTE saturation sequence, before application to perfused rat hearts at 11.7 Tesla. Results: The quasi-adiabatic pulse was insensitive to a $>2.5$-fold variation in $B_1$, producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective $B_1$. 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 ($4.24\pm0.8$ mM/s, SEM) was not significantly different from degradation flux ($6.88\pm2$ mM/s, $p=0.06$) 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. Conclusion: 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.
format Preprint
id arxiv_https___arxiv_org_abs_2008_04261
institution arXiv
publishDate 2020
record_format arxiv
spellingShingle Rapid, $B_1$-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
Lau, Justin Y. C.
Tyler, Andrew
Rodgers, Christopher
Bottomley, Paul A.
Heather, Lisa C.
Tyler, Damian J.
Medical Physics
Applied Physics
Purpose: Phosphorus saturation-transfer experiments can quantify metabolic fluxes non-invasively. 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 utilisation is currently under-explored, as it requires simultaneous saturation of inorganic phosphate (Pi) 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 Pi to enable determination of total ATP utilisation. The pulses were evaluated in Bloch equation simulations, compared with a conventional hard-cosine DANTE saturation sequence, before application to perfused rat hearts at 11.7 Tesla. Results: The quasi-adiabatic pulse was insensitive to a $>2.5$-fold variation in $B_1$, producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective $B_1$. 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 ($4.24\pm0.8$ mM/s, SEM) was not significantly different from degradation flux ($6.88\pm2$ mM/s, $p=0.06$) 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. Conclusion: 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.
title Rapid, $B_1$-insensitive, dual-band quasi-adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux
topic Medical Physics
Applied Physics
url https://arxiv.org/abs/2008.04261