Mouse skeletal muscle creatine chemical exchange saturation transfer (CrCEST) imaging at 11.7T MRI

BACKGROUND Creatine chemical exchange saturation transfer (CrCEST) imaging is expected to be a novel evaluation method of muscular energy metabolism. PURPOSE To develop CrCEST imaging of mouse skeletal muscle and to validate this technique by measuring changes in Cr concentration of ischemic hindlimbs. STUDY TYPE Prospective. ANIMAL MODEL C57BL/6 mice (n = 6), mild hindlimb ischemic mice (n = 6), and severe hindlimb ischemic mice (n = 6). FIELD STRENGTH/SEQUENCE Magnetic resonance angiography (MRA), CrCEST imaging, and phosphorus magnetic resonance spectroscopy (31 P MRS) obtained at 11.7T. ASSESSMENT MRA and 31 P MRS were performed to confirm the presence of ischemia following the compression by rubber tourniquet. CrCEST imaging was performed and magnetization transfer ratio asymmetry (MTRasym ), which reflects Cr concentration, and was calculated in severe ischemia models, mild ischemia models, and control mice. Follow-up CrCEST imaging was performed after the release of ischemia in the mild ischemia models. STATISTICAL TESTS Mean ± SD, one-way analysis of variance (ANOVA) with Tukey's HSD test, unpaired or paired t-test. RESULTS MRA revealed the loss of blood flow of the femoral artery in the ischemic hindlimb. 31 P MRS revealed different degrees of PCr decrease in severe and mild ischemic hindlimb (n = 3 per group, normal hindlimb: 1.0 ± 0, mild ischemic hindlimb: 0.77 ± 0.13, severe ischemic hindlimb: 0 ± 0). CrCEST imaging inversely revealed a significant stepwise increase in the MTRasym ratio of ischemic hindlimbs compared with controls (control, mild ischemia, and severe ischemia; 0.99 ± 0.04, 1.36 ± 0.08, and 1.59 ± 0.23, respectively, P < 0.0001). In addition, follow-up CrCEST imaging after the release of ischemia revealed normalization of the MTRasym ratios (recovered hindlimb: 1.01 ± 0.05). DATA CONCLUSION We demonstrated an increase in the MTRasym of ischemic hindlimbs, along with a decrease of PCr. We demonstrated the normalization of MTRasym after the release of ischemia and developed CrCEST imaging of mouse skeletal muscle. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:563-570.