Abstract
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 T1 relaxation effects. In this work, we aimed to extend the T1 nom method 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 T1 relaxation times and magnetization ratios among PCr, γ-ATP, and Pi. The T1 nom method 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 T1 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 31P 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 210-221 |
| Number of pages | 12 |
| Journal | Journal of Magnetic Resonance Imaging |
| Volume | 47 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2018 |
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Keywords
- T relaxation
- bioenergetics
- chemical exchange
- metabolite pool size ratios
- reaction kinetics
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
Cite this
Rapid and simultaneous measurement of phosphorus metabolite pool size ratio and reaction kinetics of enzymes in vivo. / Kim, Sang Young; Chen, Wei; Ongur, Dost; Du, Fei.
In: Journal of Magnetic Resonance Imaging, Vol. 47, No. 1, 01.2018, p. 210-221.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rapid and simultaneous measurement of phosphorus metabolite pool size ratio and reaction kinetics of enzymes in vivo
AU - Kim, Sang Young
AU - Chen, Wei
AU - Ongur, Dost
AU - Du, Fei
PY - 2018/1
Y1 - 2018/1
N2 - 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 T1 relaxation effects. In this work, we aimed to extend the T1 nom method 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 T1 relaxation times and magnetization ratios among PCr, γ-ATP, and Pi. The T1 nom method 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 T1 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 31P 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.
AB - 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 T1 relaxation effects. In this work, we aimed to extend the T1 nom method 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 T1 relaxation times and magnetization ratios among PCr, γ-ATP, and Pi. The T1 nom method 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 T1 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 31P 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.
KW - T relaxation
KW - bioenergetics
KW - chemical exchange
KW - metabolite pool size ratios
KW - reaction kinetics
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UR - http://www.scopus.com/inward/citedby.url?scp=85019135616&partnerID=8YFLogxK
U2 - 10.1002/jmri.25744
DO - 10.1002/jmri.25744
M3 - Article
C2 - 28480619
AN - SCOPUS:85019135616
VL - 47
SP - 210
EP - 221
JO - Journal of Magnetic Resonance Imaging
JF - Journal of Magnetic Resonance Imaging
SN - 1053-1807
IS - 1
ER -