Rapid and B1-insensitive absolute quantification of the CK Flux reaction with dual-band quasi-adiabatic saturation transfer with Optimal Control


Type
Article
Change log
Authors
Miller, Jack J 
Valkovic, Ladislav 
Kerr, Matthew 
Timm, Kerstin N 
Watson, William 
Abstract

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 B1, producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective B1. 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) and both measures are consistent with prior work, nonlinear error analysis highlights uncertainties in the Pi-to-ATP measurement that may explain the 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.

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Journal Title
Magnetic Resonance in Medicine
Conference Name
Journal ISSN
0740-3194
Volume Title
Publisher
Wiley
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All rights reserved
Sponsorship
Wellcome Trust (Unknown)
All authors would like to 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 programme. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. JJM would like to acknowledge a Postdoctoral Fellowship run in collaboration with Novo Nordisk and the University of Oxford, and thank financial support provided by St Hugh’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). AT would like to acknowledge funding from the Engineering and Physical Sciences Research Council (EPSRC) and Medical Research Council (MRC) [grant number EP/L016052/1]. LV also acknowledges the support of Slovak grant agencies VEGA (2/0003/20) and APVV (15‐0029). PAB was supported by a Newton Abraham Visiting professorship at Oxford.