Visualization of Spatial Distribution of Spermatogenesis in Mouse Testes Using Creatine Chemical Exchange Saturation Transfer Imaging

Yusuke Takahashi; Hidetaka Kioka; Shinichiro Fukuhara; Sohei Kuribayashi; Shigeyoshi Saito; Yoshihiro Asano; Seiji Takashima; Yoshichika Yoshioka; Yasushi Sakata

doi:10.1002/jmri.27734

Visualization of Spatial Distribution of Spermatogenesis in Mouse Testes Using Creatine Chemical Exchange Saturation Transfer Imaging

J Magn Reson Imaging. 2021 Nov;54(5):1457-1465. doi: 10.1002/jmri.27734. Epub 2021 May 30.

Authors

Affiliations

¹ Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
² Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
³ Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
⁴ Department of Medical Physics and Engineering, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
⁵ Department of Biomedical Imaging, National Cardiovascular and Cerebral Research Center, Suita, Osaka, Japan.
⁶ Department of Medical Biochemistry, Osaka University Graduate School of Frontier Bioscience, Suita, Osaka, Japan.
⁷ Laboratory of Biofunctional Imaging, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
⁸ Center for Information and Neural Networks (CiNet), Osaka University and Information and Communications Technology (NICT), Suita, Osaka, Japan.

PMID: 34056801
DOI: 10.1002/jmri.27734

Abstract

Background: When determining treatment strategies for male infertility, it is important to evaluate spermatogenesis and its spatial distribution in the testes.

Purpose: To investigate the usefulness of creatine chemical exchange saturation transfer (CrCEST) imaging for evaluating spermatogenesis and its spatial distribution.

Study type: Prospective.

Animal model: C57BL/6 control mice (n = 5) and model mice of male infertility induced by whole testis X-ray irradiation (n = 11) or localized X-ray irradiation to lower regions of testes (n = 3).

Field strength/sequence: A 11.7-T vertical-bore magnetic resonance imaging (MRI)/segmented fast low-angle shot acquisition for CEST.

Assessment: The magnetization transfer ratio for the CrCEST effect (MTR_Cr* ) was calculated in each testis of the control mice and X-ray irradiation model mice at 10, 15, 20, and 30 days after irradiation. Correlation analysis was performed between MTR_Cr* and Johnsen's score, a histological score for spermatogenesis. In the localized X-ray irradiation model, regional MTR_Cr* and Johnsen's score were calculated for correlation analysis.

Statistical tests: Unpaired t-test, one-way analysis of variance with Tukey's HSD test and Pearson's correlation analysis. A P value < 0.05 was considered statistically significant.

Results: In the irradiation model, CrCEST imaging revealed a significant linear decrease of MTR_Cr* after irradiation (control, 8.7 ± 0.6; 10 days, 7.9 ± 0.8; 15 days, 6.5 ± 0.6; 20 days, 5.4 ± 1.0; 30 days, 4.4 ± 0.8). A significant linear correlation was found between MTR_Cr* and Johnsen's score (Pearson's correlation coefficient (r) = 0.79). In the localized irradiation model, CrCEST imaging visualized a significant regional decrease of MTR_Cr* in the unshielded region (shielded, 6.9 ± 0.7; unshielded, 4.9 ± 1.0), and a significant linear correlation was found between regional MTR_Cr* and Johnsen's score (r = 0.78).

Data conclusion: Testicular CrCEST effects correlated well with spermatogenesis. CrCEST imaging was useful for evaluating spermatogenesis and its spatial distribution.

Evidence level: 2 TECHNICAL EFFICACY: Stage 2.

Keywords: azoospermia; chemical exchange saturation transfer; creatine; male infertility; spermatogenesis; testis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Creatine*
Male
Mice
Mice, Inbred C57BL
Prospective Studies
Spermatogenesis
Testis* / diagnostic imaging

Substances

Creatine