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. 2015 Feb;73(2):726-30.
doi: 10.1002/mrm.25136. Epub 2014 Feb 12.

Brain high-energy phosphates and creatine kinase synthesis rate under graded isoflurane anesthesia: An in vivo (31) P magnetization transfer study at 11.7 tesla

Andrew Bresnen  1 , Timothy Q Duong
Affiliations

Brain high-energy phosphates and creatine kinase synthesis rate under graded isoflurane anesthesia: An in vivo (31) P magnetization transfer study at 11.7 tesla

Andrew Bresnen et al. Magn Reson Med. 2015 Feb.

Abstract

Purpose: The creatine kinase rate of metabolic adenosine triphosphate (ATP) synthesis is an important metabolic parameter but is challenging to measure in vivo due to limited signal-to-noise ratio and long measurement time.

Theory and methods: This study reports the implementation of an accelerated (31) P Four Angle Saturation Transfer (FAST) method to measure the forward creatine kinase (CK) rate of ATP synthesis. Along with a high-field scanner (11.7 Tesla) and a small sensitive surface coil, the forward CK rate in the rat brain was measured in ∼5 min.

Results: Under 1.2% isoflurane, the forward CK rate constant and metabolic flux were, respectively, kf , CK =0.26 ± 0.02 s(-1) and Ff,CK =70.8 ± 4.6 μmol/g/min. As a demonstration of utility and sensitivity, measurements were made under graded isoflurane. Under 2.0% isoflurane, kf , CK =0.16 ± 0.02 s(-1) and Ff,CK =410.0 ± 4.2 μmol/g/min, corresponding to a 38% and 42% reduction, respectively, relative to 1.2% isoflurane. By contrast, the ATP and phosphocreatine concentrations were unaltered.

Conclusion: This study demonstrated the (31) P FAST measurement of creatine kinase rate of ATP synthesis in rat brain with reasonable temporal resolution. Different isoflurane levels commonly used in animal models significantly alter the CK reaction rate but not ATP and phosphocreatine concentrations.

Keywords: MRS; high fields; metabolic flux; rats.

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Conflict of interest statement

Disclosure/Conflict of Interest: The authors declare no conflict of interest

Figures

Figure 1
Figure 1. Modulation of BIR4 Excitation Pulses
Three graphs of TANH/TAN modulation of the BIR4 pulses used for 31P excitation (a) amplitude B1, (b) frequency ω, (c) phase Φ. the discontinuity of the phase modulations after segment 1 and 3 determine the flip angle.
Figure 2
Figure 2. Square versus BIR4 RF Pulse
In vivo 31P spectra acquired using a (a) square and (b) BIR4 pulse. With the square pulse, the 31P spectrum is heavily contaminated by phospholipid signal. With BIR4, phospholipid signal was eliminated, improving quantification of all metabolites.
Figure 3
Figure 3. Saturation Recovery using BIRP and BIR4 ±30
T1 measurements of inorganic phosphorus made on a dead rat brain. BIR4 T1 measurements are skewed due to positive or negative contributions of phospholipid signal.
Figure 4
Figure 4
31P FAST spectra using flip angles of 60° and 30° with and without saturation of γ-ATP (in vivo whole brain).
See this image and copyright information in PMC

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