Rapid and simultaneous measurement of phosphorus metabolite pool size ratio and reaction kinetics of enzymes in vivo
Year: 2017
Type: article
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 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 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.
DOI: 10.1002/jmri.25744
Authors: Sang‐Young Kim, Wei Chen, Dost Ongur, Fei Du
Institutions: Harvard University, McLean Hospital, University of Minnesota
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Advancing MRI & MRS Technologies for Studying Human Brain Function and Energetics, Novel 31P MRS Approach for Measuring Abnormal Bioenergetics in Schizophrenia, Research and Mentoring on Brain and Peripheral Bioenergetics in Schizophrenia, Probing the White Matter in Schizophrenia Using Novel MRS Techniques, Quantitative and Non-invasive Imaging of Oxygen Metabolism in Human Brain, An MRI based in vivo measure of glutamatergic synaptic neurotransmission
OpenAlex ID: W2612396435