Purpose To develop a 31P spectroscopic magnetic resonance fingerprinting (MRF) method for fast quantification of the chemical exchange rate between phosphocreatine (PCr) and ATP via creatine kinase (CK). Methods A 31P 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 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 to magnetization transfer (MT-MRS) method in rat hindlimb at 9.4 T (n=17). Reproducibility of CK-MRF was also assessed by comparing CK-MRF measurements to both MT-MRS (n=17) and four angle saturation transfer (FAST) methods (n=7). Results Simulation results showed that CK-MRF quantification of kfCK was robust with <5% error in the presence of model inaccuracies including dictionary resolution, metabolite T2 values, Pi 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. Conclusion This study demonstrates the potential of a 31P spectroscopic MRF framework for rapid, accurate and reproducible quantification of chemical exchange rate of CK in vivo.

Magnetic resonance fingerprinting (MRF) is a method to extract quantitative tissue properties such as T1 and T2 relaxation rates from arbitrary pulse sequences using conventional MRI hardware. MRF pulse sequences have thousands of tunable parameters, which can be chosen to maximize precision and minimize scan time. Here, we perform de novo automated design of MRF pulse sequences by applying physics-inspired optimization heuristics. Our experimental data suggest that systematic errors dominate over random errors in MRF scans under clinically relevant conditions of high undersampling. Thus, in contrast to prior optimization efforts, which focused on statistical error models, we use a cost function based on explicit first-principles simulation of systematic errors arising from Fourier undersampling and phase variation. The resulting pulse sequences display features qualitatively different from previously used MRF pulse sequences and achieve fourfold shorter scan time than prior human-designed sequences of equivalent precision in T1 and T2. Furthermore, the optimization algorithm has discovered the existence of MRF pulse sequences with intrinsic robustness against shading artifacts due to phase variation.

Background Quantitative T1 and T2 mapping in the abdomen provides valuable information in tissue characterization but is technically challenging due to respiratory motions. The proposed technique integrates magnetic resonance fingerprinting (MRF) and pilot tone (PT) navigator with retrospective gating to provide simultaneous quantification of multiple tissue properties in a single acquisition without breath‐holding or patient set‐up. Purpose To develop a free‐breathing abdominal MRF technique for quantitative mapping in the abdomen. Study Type Prospective. Population Twelve healthy volunteers. Field Strength/Sequence A 3 T, two‐dimensional (2D) and three‐dimensional (3D) spiral MRF sequence with fast imaging with steady‐state free precession (FISP) readout. Assessment The PT navigator was compared to standard respiratory belt performance. The T1 and T2 values acquired using 2D and 3D MRF with and without PT were obtained in a phantom and compared to reference values. Digital phantom simulation was performed to evaluate PT MRF reconstruction with varying breathing patterns. In the in vivo studies, T1 and T2 values derived from PT 2D MRF were compared to 2D breath‐hold MRF. T1 and T2 values derived from PT 3D MRF were compared to published values. Statistical Tests Principal component analysis (PCA), linear regression, relative error, Pearson correlation, paired Student's t‐test, Bland–Altman Analysis. Results The phantom study showed PT MRF T1 values had a mean difference of 0.2% ± 0.1%, and T2 values had a mean difference of 0.1% ± 0.4% when compared to no‐PT MRF values. The digital phantom experiment suggested the T1 and T2 maps at both end‐exhalation and end‐inhalation states resemble the corresponding ground‐truth maps. Data conclusion The phantom study showed good agreement between MRF T1 and T2 values and with reference values. In vivo studies demonstrated that 2D and 3D quantitative imaging in the abdomen could be achieved with integration of PT navigation with MRF reconstruction using retrospective gating of respiratory motion. Evidence Level 1 Technical Efficacy Stage 1

To enable non-invasive dynamic metabolic mapping in rodent model studies of mitochondrial function using 31 P-MR spectroscopic imaging (MRSI). Methods: We developed a novel method for high-resolution dynamic 31 P-MRSI. The method synergistically integrates physics-based models of spectral structures, biochemical modeling of molecular dynamics, and subspace learning to capture spatiospectral variations. Fast data acquisition was achieved using rapid spiral trajectories and sparse sampling of (k, t, T)-space; image reconstruction was accomplished using a low-rank tensor-based framework. Results: The proposed method provided high-resolution dynamic metabolic mapping in rat hindlimb at spatial and temporal resolutions of 4 × 4 × 2 mm 3 and 1.28 s, respectively. This allowed for in vivo mapping of the time-constant of phosphocreatine resynthesis, a well established index of mitochondrial oxidative capacity. Multiple rounds of in vivo experiments were performed to demonstrate reproducibility, and in vitro experiments were used to validate the accuracy of the estimated metabolite maps. Conclusions: A new model-based method is proposed to achieve high-resolution dynamic 31 P-MRSI. The proposed method's ability to delineate metabolic heterogeneity was demonstrated in rat hindlimb. Significance: Abnormal mitochondrial metabolism is a key cellular dysfunction in many prevalent diseases such as diabetes and heart disease; however, current understanding of mitochondrial function is mostly gained from studies on isolated mitochondria

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.