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Quantification of creatine kinase reaction rate in mouse hindlimb using phosphorus-31 magnetic resonance spectroscopic fingerprinting.

ABSTRACT: The goal of this study was to evaluate the accuracy, reproducibility, and efficiency of a ³¹ P magnetic resonance spectroscopic fingerprinting (³¹ P-MRSF) method for fast quantification of the forward rate constant of creatine kinase (CK) in mouse hindlimb. The ³¹ P-MRSF method acquired spectroscopic fingerprints using interleaved acquisition of phosphocreatine (PCr) and γATP with ramped flip angles and a saturation scheme sensitive to chemical exchange between PCr and γATP. Parameter estimation was performed by matching the acquired fingerprints to a dictionary of simulated fingerprints generated from the Bloch-McConnell model. The accuracy of ³¹ P-MRSF measurements was compared with the magnetization transfer (MT-MRS) method in mouse hindlimb at 9.4 T (n = 8). The reproducibility of ³¹ P-MRSF was also assessed by repeated measurements. Estimation of the CK rate constant using ³¹ P-MRSF (0.39 ± 0.03 s^-1 ) showed a strong agreement with that using MT-MRS measurements (0.40 ± 0.05 s^-1 ). Variations less than 10% were achieved with 2 min acquisition of ³¹ P-MRSF data. Application of the ³¹ P-MRSF method to mice subjected to an electrical stimulation protocol detected an increase in CK rate constant in response to stimulation-induced muscle contraction. These results demonstrated the potential of the ³¹ P-MRSF framework for rapid, accurate, and reproducible quantification of the chemical exchange rate of CK in vivo.

SUBMITTER: Kim K

PROVIDER: S-EPMC8324327 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The purpose of this work was to develop a 31 P spectroscopic magnetic resonance fingerprinting (MRF) method for fast quantification of the chemical exchange rate between phosphocreatine (PCr) and adenosine triphosphate (ATP) via creatine kinase (CK). A 31 P MRF sequence (CK-MRF) was developed to quantify the forward rate constant of ATP synthesis via CK ( kfCK), the T1 relaxation time of PCr ( T1PCr), and the PCr-to-ATP concentration ratio ( MRPCr). The CK-MRF sequence used a balanced steady-state free precession (bSSFP)-type excitation with ramped flip angles and a unique saturation scheme sensitive to the exchange between PCr and γATP. Parameter estimation was accomplished by matching the acquired signals to a dictionary generated using the Bloch-McConnell equation. Simulation studies were performed to examine the susceptibility of the CK-MRF method to several potential error sources. The accuracy of nonlocalized CK-MRF measurements before and after an ischemia-reperfusion (IR) protocol was compared with the magnetization transfer (MT-MRS) method in rat hindlimb at 9.4 T (n = 14). The reproducibility of CK-MRF was also assessed by comparing CK-MRF measurements with both MT-MRS (n = 17) and four angle saturation transfer (FAST) (n = 7). Simulation results showed that CK-MRF quantification of kfCK was robust, with less than 5% error in the presence of model inaccuracies including dictionary resolution, metabolite T2 values, inorganic phosphate metabolism, and B1 miscalibration. Estimation of kfCK by CK-MRF (0.38 ± 0.02 s-1 at baseline and 0.42 ± 0.03 s-1 post-IR) showed strong agreement with MT-MRS (0.39 ± 0.03 s-1 at baseline and 0.44 ± 0.04 s-1 post-IR). kfCK estimation was also similar between CK-MRF and FAST (0.38 ± 0.02 s-1 for CK-MRF and 0.38 ± 0.11 s-1 for FAST). The coefficient of variation from 20 s CK-MRF quantification of kfCK was 42% of that by 150 s MT-MRS acquisition and was 12% of that by 20 s FAST acquisition. This study demonstrates the potential of a 31 P spectroscopic MRF framework for rapid, accurate and reproducible quantification of chemical exchange rate of CK in vivo.

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Quantification of creatine kinase reaction rate in mouse hindlimb using phosphorus-31 magnetic resonance spectroscopic fingerprinting.

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