Evaluating the Cisplatin Dose Dependence of Testicular Dysfunction Using Creatine Chemical Exchange Saturation Transfer Imaging

Abstract

Chemical exchange saturation transfer (CEST) imaging is a non-invasive molecular imaging technique for indirectly measuring low-concentration endogenous metabolites. Conventional CEST has low specificity, owing to the effects of spillover, magnetization transfer (MT), and T1 relaxation, thus necessitating an inverse Z-spectrum analysis. We aimed to investigate the usefulness of inverse Z-spectrum analysis in creatine (Cr)-CEST in mice, by conducting preclinical 7T-magnetic resonance imaging (MRI) and comparing the conventional analysis metric magnetization transfer ratio (MTRconv) with the novel metric apparent exchange-dependent relaxation (AREX). We performed Cr-CEST imaging using 7T-MRI on mouse testes, using C57BL/6 mice as the control and a cisplatin-treated model. We prepared different doses of cisplatin to observe its dose dependence effect on testicular function. CEST imaging was obtained using an MT pulse with varying saturation frequencies, ranging from −4.8 ppm to +4.8 ppm. The application of control mouse testes improved the specificity of the CEST effect and image contrast between the testes and testicular epithelium. The cisplatin-treated model revealed impaired testicular function, and the Cr-CEST imaging displayed decreased Cr levels in the testes. There was a significant difference between the low- and high-dose models. The MTR values of Cr-CEST reflected the cisplatin dose dependence of testicular dysfunction.