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

Yusuke Takahashi; Shigeyoshi Saito; Hidetaka Kioka; Rikita Araki; Yoshihiro Asano; Seiji Takashima; Yasushi Sakata; Yoshichika Yoshioka

doi:10.1002/jmri.26844

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

J Magn Reson Imaging. 2020 Feb;51(2):563-570. doi: 10.1002/jmri.26844. Epub 2019 Jun 22.

Authors

Yusuke Takahashi¹, Shigeyoshi Saito^{2

3}, Hidetaka Kioka¹, Rikita Araki⁴, Yoshihiro Asano¹, Seiji Takashima⁵, Yasushi Sakata¹, Yoshichika Yoshioka^{6

7}

Affiliations

¹ Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
² Department of Medical Physics and Engineering, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
³ Department of Biomedical Imaging, National Cardiovascular and Cerebral Research Center, Suita, Osaka, Japan.
⁴ BioSpin Division, Bruker Japan K.K., Yokohama, Kanagawa, Japan.
⁵ Department of Medical Biochemistry, Osaka University Graduate School of Frontier Bioscience, Suita, Osaka, Japan.
⁶ Laboratory of Biofunctional Imaging, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
⁷ Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Osaka, Japan.

PMID: 31228359
DOI: 10.1002/jmri.26844

Abstract

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 (MTR_asym ), 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 MTR_asym 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 MTR_asym ratios (recovered hindlimb: 1.01 ± 0.05).

Data conclusion: We demonstrated an increase in the MTR_asym of ischemic hindlimbs, along with a decrease of PCr. We demonstrated the normalization of MTR_asym 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.

Keywords: chemical exchange saturation transfer; creatine; hindlimb ischemia; magnetic resonance imaging; phosphorus magnetic resonance spectroscopy.

MeSH terms

Animals
Creatine*
Hindlimb
Ischemia / diagnostic imaging
Magnetic Resonance Imaging
Mice
Mice, Inbred C57BL
Muscle, Skeletal* / diagnostic imaging
Prospective Studies

Substances

Creatine