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2015 ; 28
(11
): 1455-62
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(31)P-MRS of healthy human brain: ATP synthesis, metabolite concentrations, pH,
and T1 relaxation times
#MMPMID26404723
Ren J
; Sherry AD
; Malloy CR
NMR Biomed
2015[Nov]; 28
(11
): 1455-62
PMID26404723
show ga
The conventional method for measuring brain ATP synthesis is (31)P saturation
transfer (ST), a technique typically dependent on prolonged pre-saturation with
?-ATP. In this study, ATP synthesis rate in resting human brain is evaluated
using EBIT (exchange kinetics by band inversion transfer), a technique based on
slow recovery of ?-ATP magnetization in the absence of B1 field following
co-inversion of PCr and ATP resonances with a short adiabatic pulse. The
unidirectional rate constant for the Pi ? ?-ATP reaction is 0.21 ± 0.04?s(-1) and
the ATP synthesis rate is 9.9 ± 2.1?mmol?min(-1) ?kg(-1) in human brain (n = 12
subjects), consistent with the results by ST. Therefore, EBIT could be a useful
alternative to ST in studying brain energy metabolism in normal physiology and
under pathological conditions. In addition to ATP synthesis, all detectable (31)P
signals are analyzed to determine the brain concentration of phosphorus
metabolites, including UDPG at around 10?ppm, a previously reported resonance in
liver tissues and now confirmed in human brain. Inversion recovery measurements
indicate that UDPG, like its diphosphate analogue NAD, has apparent T1 shorter
than that of monophosphates (Pi, PMEs, and PDEs) but longer than that of
triphosphate ATP, highlighting the significance of the (31)P-(31)P dipolar
mechanism in T1 relaxation of polyphosphates. Another interesting finding is the
observation of approximately 40% shorter T1 for intracellular Pi relative to
extracellular Pi, attributed to the modulation by the intracellular phosphoryl
exchange reaction Pi ? ?-ATP. The sufficiently separated intra- and extracellular
Pi signals also permit the distinction of pH between intra- and extracellular
environments (pH?7.0 versus pH?7.4). In summary, quantitative (31)P MRS in
combination with ATP synthesis, pH, and T1 relaxation measurements may offer a
promising tool to detect biochemical alterations at early stages of brain
dysfunctions and diseases.