31P MR spectroscopy and computational modeling identify a direct relation between Pi content of an alkaline compartment in resting muscle and phosphocreatine resynthesis kinetics in active muscle in humans.

The assessment of mitochondrial properties in skeletal muscle is important in clinical research, for instance in the study of diabetes. The gold standard to measure mitochondrial capacity non-invasively is the phosphocreatine (PCr) recovery rate after exercise, measured by (31)P Magnetic Resonance s...

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Autores principales:	Joep W M van Oorschot, Joep P J Schmitz, Andrew Webb, Klaas Nicolay, Jeroen A L Jeneson, Hermien E Kan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7298a0deb83641a9944e71f8651acd4b
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spelling	oai:doaj.org-article:7298a0deb83641a9944e71f8651acd4b2021-11-18T08:53:20Z31P MR spectroscopy and computational modeling identify a direct relation between Pi content of an alkaline compartment in resting muscle and phosphocreatine resynthesis kinetics in active muscle in humans.1932-620310.1371/journal.pone.0076628https://doaj.org/article/7298a0deb83641a9944e71f8651acd4b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24098796/?tool=EBIhttps://doaj.org/toc/1932-6203The assessment of mitochondrial properties in skeletal muscle is important in clinical research, for instance in the study of diabetes. The gold standard to measure mitochondrial capacity non-invasively is the phosphocreatine (PCr) recovery rate after exercise, measured by (31)P Magnetic Resonance spectroscopy ((31)P MRS). Here, we sought to expand the evidence base for an alternative method to assess mitochondrial properties which uses (31)P MRS measurement of the Pi content of an alkaline compartment attributed to mitochondria (Pi2; as opposed to cytosolic Pi (Pi1)) in resting muscle at high magnetic field. Specifically, the PCr recovery rate in human quadriceps muscle was compared with the signal intensity of the Pi2 peak in subjects with varying mitochondrial content of the quadriceps muscle as a result of athletic training, and the results were entered into a mechanistic computational model of mitochondrial metabolism in muscle to test if the empirical relation between Pi2/Pi1 ratio and the PCr recovery was consistent with theory. Localized (31)P spectra were obtained at 7T from resting vastus lateralis muscle to measure the intensity of the Pi2 peak. In the endurance trained athletes a Pi2/Pi1 ratio of 0.07 ± 0.01 was found, compared to a significantly lower (p<0.05) Pi2/Pi1 ratio of 0.03 ± 0.01 in the normally active group. Next, PCr recovery kinetics after in magnet bicycle exercise were measured at 1.5T. For the endurance trained athletes, a time constant τPCr 12 ± 3 s was found, compared to 24 ± 5s in normally active subjects. Without any parameter optimization the computational model prediction matched the experimental data well (r(2) of 0.75). Taken together, these results suggest that the Pi2 resonance in resting human skeletal muscle observed at 7T provides a quantitative MR-based functional measure of mitochondrial density.Joep W M van OorschotJoep P J SchmitzAndrew WebbKlaas NicolayJeroen A L JenesonHermien E KanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e76628 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joep W M van Oorschot Joep P J Schmitz Andrew Webb Klaas Nicolay Jeroen A L Jeneson Hermien E Kan 31P MR spectroscopy and computational modeling identify a direct relation between Pi content of an alkaline compartment in resting muscle and phosphocreatine resynthesis kinetics in active muscle in humans.
description	The assessment of mitochondrial properties in skeletal muscle is important in clinical research, for instance in the study of diabetes. The gold standard to measure mitochondrial capacity non-invasively is the phosphocreatine (PCr) recovery rate after exercise, measured by (31)P Magnetic Resonance spectroscopy ((31)P MRS). Here, we sought to expand the evidence base for an alternative method to assess mitochondrial properties which uses (31)P MRS measurement of the Pi content of an alkaline compartment attributed to mitochondria (Pi2; as opposed to cytosolic Pi (Pi1)) in resting muscle at high magnetic field. Specifically, the PCr recovery rate in human quadriceps muscle was compared with the signal intensity of the Pi2 peak in subjects with varying mitochondrial content of the quadriceps muscle as a result of athletic training, and the results were entered into a mechanistic computational model of mitochondrial metabolism in muscle to test if the empirical relation between Pi2/Pi1 ratio and the PCr recovery was consistent with theory. Localized (31)P spectra were obtained at 7T from resting vastus lateralis muscle to measure the intensity of the Pi2 peak. In the endurance trained athletes a Pi2/Pi1 ratio of 0.07 ± 0.01 was found, compared to a significantly lower (p<0.05) Pi2/Pi1 ratio of 0.03 ± 0.01 in the normally active group. Next, PCr recovery kinetics after in magnet bicycle exercise were measured at 1.5T. For the endurance trained athletes, a time constant τPCr 12 ± 3 s was found, compared to 24 ± 5s in normally active subjects. Without any parameter optimization the computational model prediction matched the experimental data well (r(2) of 0.75). Taken together, these results suggest that the Pi2 resonance in resting human skeletal muscle observed at 7T provides a quantitative MR-based functional measure of mitochondrial density.
format	article
author	Joep W M van Oorschot Joep P J Schmitz Andrew Webb Klaas Nicolay Jeroen A L Jeneson Hermien E Kan
author_facet	Joep W M van Oorschot Joep P J Schmitz Andrew Webb Klaas Nicolay Jeroen A L Jeneson Hermien E Kan
author_sort	Joep W M van Oorschot
title	31P MR spectroscopy and computational modeling identify a direct relation between Pi content of an alkaline compartment in resting muscle and phosphocreatine resynthesis kinetics in active muscle in humans.
title_short	31P MR spectroscopy and computational modeling identify a direct relation between Pi content of an alkaline compartment in resting muscle and phosphocreatine resynthesis kinetics in active muscle in humans.
title_full	31P MR spectroscopy and computational modeling identify a direct relation between Pi content of an alkaline compartment in resting muscle and phosphocreatine resynthesis kinetics in active muscle in humans.
title_fullStr	31P MR spectroscopy and computational modeling identify a direct relation between Pi content of an alkaline compartment in resting muscle and phosphocreatine resynthesis kinetics in active muscle in humans.
title_full_unstemmed	31P MR spectroscopy and computational modeling identify a direct relation between Pi content of an alkaline compartment in resting muscle and phosphocreatine resynthesis kinetics in active muscle in humans.
title_sort	31p mr spectroscopy and computational modeling identify a direct relation between pi content of an alkaline compartment in resting muscle and phosphocreatine resynthesis kinetics in active muscle in humans.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7298a0deb83641a9944e71f8651acd4b
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31P MR spectroscopy and computational modeling identify a direct relation between Pi content of an alkaline compartment in resting muscle and phosphocreatine resynthesis kinetics in active muscle in humans.

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