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Rapid and simultaneous measurement of phosphorus metabolite pool size ratio and reaction kinetics of enzymes in vivo
Author(s) -
Kim SangYoung,
Chen Wei,
Ongur Dost,
Du Fei
Publication year - 2018
Publication title -
journal of magnetic resonance imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.563
H-Index - 160
eISSN - 1522-2586
pISSN - 1053-1807
DOI - 10.1002/jmri.25744
Subject(s) - phosphocreatine , metabolite , relaxation (psychology) , in vivo , chemistry , bioenergetics , pi , magnetization , analytical chemistry (journal) , nuclear magnetic resonance , biochemistry , energy metabolism , chromatography , physics , biology , microbiology and biotechnology , quantum mechanics , neuroscience , mitochondrion , endocrinology , magnetic field
Purpose The metabolites phosphocreatine (PCr), adenosine triphosphate (ATP), and in‐organic phosphate (Pi) are biochemically coupled. Their pool sizes, assessed by their magnetization ratios, have been extensively studied and reflect bioenergetics status in vivo. However, most such studies have ignored chemical exchange and T 1 relaxation effects. In this work, we aimed to extend theT 1 n o mmethod to simultaneously quantify the reaction rate constants as well as phosphorus metabolite pool size ratios under partially relaxed conditions. Materials and Methods Modified Bloch‐McConnell equations were used to simulate the effects of chemical exchanges on T 1 relaxation times and magnetization ratios among PCr, γ‐ATP, and Pi. TheT 1 n o mmethod with iteration approach was used to measure both reaction constants and metabolite pool size ratios. To validate our method, in vivo data from rat brains (N = 8) at 9.4 Tesla were acquired under two conditions, i.e., approximately full relaxation ( TR = 9 s) and partial relaxation ( TR = 3 s). We compared metabolite pool size ratios and reaction constants before and after correcting the chemical exchange and T 1 relaxation effects. Results There were significant errors in underestimation of PCr/γATP by 12 % ( P = 0.03) and overestimation of ATP/Pi ratios by 14 % ( P = 0.04) when not considering chemical exchange effects. These errors were minimized using our iteration approach, resulting in no significant differences (PCr/γATP, P = 0.47; ATP/Pi, P = 0.81) in metabolite pool size ratios and reaction constants between the two measurements (i.e., short versus long TR conditions). Conclusion Our method can facilitate broad biomedical applications of 31 P magnetization saturation transfer spectroscopy, requiring high temporal and/or spatial resolution for assessment of altered bioenergetics. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:210–221.