31 P magnetic resonance fingerprinting for rapid quantification of creatine kinase reaction rate in vivo

Abstract

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.

Keywords: 31P spectroscopy; creatine kinase metabolism; ischemia/reperfusion; magnetic resonance fingerprinting.