Jack J Miller1,2,3,4, Ladislav Valkovič3,5, Matthew Kerr2, Kerstin N Timm2, William D Watson3, Justin Y C Lau2,3, Andrew Tyler2,3, Christopher Rodgers3,6, Paul A Bottomley3,7, Lisa C Heather2, Damian J Tyler2,3. 1. Department of Physics, University of Oxford, Oxford, UK. 2. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. 3. Oxford Centre for Clinical Magnetic Resonance Research, John Radcliffe Hospital, Headington, Oxford, UK. 4. Health, Aarhus University, Aarhus, Denmark. 5. Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia. 6. Wolfson Brain Imaging Centre, University of Cambridge, Oxford, UK. 7. Division of MR Research, Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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 ( 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 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 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, 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.
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 ( 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 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 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, 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.
Authors: Felix A Breuer; Martin Blaimer; Matthias F Mueller; Nicole Seiberlich; Robin M Heidemann; Mark A Griswold; Peter M Jakob Journal: Magn Reson Med Date: 2006-03 Impact factor: 4.668
Authors: 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 Journal: Magn Reson Med Date: 2021-02-03 Impact factor: 3.737
Authors: 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 Journal: Magn Reson Med Date: 2021-02-03 Impact factor: 3.737
Authors: M Kerr; K M J H Dennis; C A Carr; W Fuller; G Berridge; S Rohling; C L Aitken; C Lopez; R Fischer; J J Miller; K Clarke; D J Tyler; L C Heather Journal: FASEB J Date: 2021-08 Impact factor: 5.191