A Pilot Study of Ratiometric Creatine CEST MRI Assessment of Rabbit Skeletal Muscle Energy Metabolism at 3 T.

BACKGROUND: pH MRI may provide useful information to evaluate metabolic disruption following ischemia. Radiofrequency amplitude-based creatine chemical exchange saturation transfer (CrCEST) ratiometric MRI is pH-sensitive, which could but has not been explored to examine muscle ischemia. PURPOSE: To investigate skeletal muscle energy metabolism alterations with CrCEST ratiometric MRI. STUDY TYPE: Prospective. ANIMAL MODEL: Seven adult New Zealand rabbits with ipsilateral hindlimb muscle ischemia. FIELD STRENGTH/SEQUENCE: 3 T/two MRI scans, including MRA and CEST imaging, were performed under two B1 amplitudes of 0.5 and 1.25 µT after 2 hours of hindlimb muscle ischemia and 1 hour of reperfusion recovery, respectively. ASSESSMENT: CEST effects of two energy metabolites of creatine and phosphocreatine (PCrCEST) were resolved with the multipool Lorentzian fitting approach. The pixel-wise CrCEST ratio was quantified by calculating the ratio of the resolved CrCEST peaks under a B1 amplitude of 1.25 µT to those under 0.5 µT in the entire muscle. STATISTICAL TESTS: One-way ANOVA and Pearson's correlation. P < 0.05 was considered statistically significant. RESULTS: MRA images confirmed the blood flow loss and restoration in the ischemic hindlimb at the ischemia and recovery phases, respectively. Ischemic muscles exhibited a significant decrease of PCr at the ischemia (under both B1 amplitudes) and recovery phases (under B1 amplitude of 0.5 µT) and significantly increased CrCEST from normal tissues at both phases (under both B1 levels). Specifically, CrCEST decreased, and PCrCEST increased with the CrCEST ratio. Significantly strong correlations were observed among the CrCEST ratio, and CrCEST and PCrCEST under both B1 levels (r > 0.80). DATA CONCLUSION: The CrCEST ratio altered substantially with muscle pathological states and was closely related to CEST effects of energy metabolites of Cr and PCr, suggesting that the pH-sensitive CrCEST ratiometric MRI is feasible to evaluate muscle injuries at the metabolic level. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1.

Numerical simulation-based assessment of pH-sensitive chemical exchange saturation transfer MRI quantification accuracy across field strengths.

Chemical exchange saturation transfer (CEST) MRI detects dilute labile protons via their exchange with bulk water, conferring pH sensitivity. Based on published exchange and relaxation properties, a 19-pool simulation was used to model the brain pH-dependent CEST effect and assess the accuracy of quantitative CEST (qCEST) analysis across magnetic field strengths under typical scan conditions. First, the optimal B1 amplitude was determined by maximizing pH-sensitive amide proton transfer (APT) contrast under the equilibrium condition. Apparent and quasi-steady-state (QUASS) CEST effects were then derived under the optimal B1 amplitude as functions of pH, RF saturation duration, relaxation delay, Ernst flip angle, and field strength. Finally, CEST effects, particularly the APT signal, were isolated with spinlock model-based Z-spectral fitting to evaluate the accuracy and consistency of CEST quantification. Our data showed that QUASS reconstruction significantly improved the consistency between simulated and equilibrium Z-spectra. The residual difference between QUASS and equilibrium CEST Z-spectra was, on average, 30 times less than that of the apparent CEST Z-spectra across field strengths, saturation, and repetition times. Also, the spinlock fitting of the QUASS CEST effect significantly reduced the residual errors 9-fold. Furthermore, the isolated APT amplitude from QUASS reconstruction was consistent and higher than the apparent CEST analysis under nonequilibrium conditions. To summarize, this study confirmed that QUASS reconstruction facilitates accurate determination of the CEST system under different scan protocols across field strengths, with the potential to help standardize CEST quantification.

In Vitro and In Vivo Assessment of Nonionic Iodinated Radiographic Molecules as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Tumor Perfusion Agents.

OBJECTIVES: The aim of this study was to evaluate 4 nonionic x-ray iodinated contrast agents (CAs), commonly used in radiographic procedures, as novel chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) agents by assessing their in vitro exchange properties and preliminary in vivo use as tumor enhancing agents. MATERIALS AND METHODS: The CEST properties, as function of pH (range, 5.5-7.9) and of radio frequency conditions (irradiation field strength range of 1-9 µT and time of 1-9 seconds), have been determined at 7 T and 310 K for 4 x-ray CAs commonly used in clinical settings, namely, iomeprol, iohexol, ioversol, and iodixanol. Their in vivo properties have been investigated upon intravenous injection in a murine HER2+ breast tumor model (n = 4 mice for each CA) using both computed tomography (CT) and MRI modalities. RESULTS: The prototropic exchange rates measured for the 4 investigated iodinated molecules showed strong pH dependence with base catalyzed exchange rate that was faster for monomeric compounds (20-4000 Hz in the pH range of 5.5-7.9). Computed tomography quantification showed marked (up to 2 mg I/mL concentration) and prolonged accumulation (up to 30 minutes postinjection) inside tumor regions. Among the 4 agents we tested, iohexol and ioversol display good CEST contrast properties at 7 T, and in vivo results confirmed strong and prolonged contrast enhancement of the tumors, with elevated extravasation fractions (74%-91%). A strong and significant correlation was found between CT and CEST-MRI tumor-enhanced images (R = 0.70, P < 0.01). CONCLUSIONS: The obtained results demonstrate that iohexol and ioversol, 2 commonly used radiographic compounds, can be used as MRI perfusion agents, particularly useful when serial images acquisitions are needed to complement CT information.