Creatine Chemical Exchange Saturation Transfer (Cr-CEST) Imaging Can Evaluate Cisplatin-induced Testicular Damage

Abstract

Purpose: This study aimed to investigate the ability of creatine-chemical exchange saturation transfer (Cr-CEST) technique assessed through 7-T MRI to evaluate cisplatin-induced testicular damage.

Methods: We used 8-10 weeks C57BL/6 mice (n = 10) that were divided into a control group (n = 5) and a cisplatin-treated group (n = 5). The cisplatin group received cisplatin at a dose of 15 mg/kg, via intraperitoneal injection, while the control group received saline. MR images of mouse testes were acquired under anesthesia 18 days after the injection using a horizontal 7-T scanner. The pulse sequence consisted of rapid acquisition with a relaxation enhancement (RARE) with magnetization transfer. The Z-spectra were collected using a 2000-ms saturation pulse at a B₁ amplitude of 1.2 μT, with frequencies varying from -4.8 to +4.8 parts per million (ppm). Maps of magnetization transfer ratio with asymmetric analysis (MTR_asym) were reconstructed at a Cr metabolite concentration of 1.8 ppm.

Results: The Cr-CEST effect was significantly reduced in the cisplatin-treated group compared to the control group (MTR_asym of control mice vs. cisplatin-treated mice: 6.9 [6-7.5] vs. 5.2 [4-5.5], P = 0.008). Correlation analysis revealed a strong correlation between the Cr-CEST effect and the pathological score (ρ = 0.93, P < 0.001).

Conclusion: Cr-CEST MRI can be useful for the evaluation of cisplatin-induced testicular damage in mice.

Keywords: chemical exchange saturation transfer; cisplatin; creatine; testes.

Fig. 1

In vivo Cr-CEST imaging of mice testes. (a and c) Anatomical imaging and (b and d) MTR asym map at 1.8 ppm. MTR asym map showed lower Cr-CEST effect in a cisplatin-treated mouse than a control mouse. asym, asymmetry; Cr-CEST, creatine-chemical exchange saturation transfer; MTR, magnetization transfer ratio; T2WI, T2-weighted imaging.

Fig. 2

(a and b) In vivo Z-spectrum analysis and (c and d) magnetization transfer ratio asymmetry plot of the testes of cisplatin-treated and control mice (5 animals in each group). The variation bars in the figures are maximum and minimum. asym, asymmetry; MTR, magnetization transfer ratio.

Fig. 3

Histopathological analysis of the seminiferous epithelium in (a) cisplatin-treated mice and (b) controls. Cisplatin-treated mice (a) show disorganization of the cytoarchitecture of the seminiferous epithelium, vacuolization (arrows).

Fig. 4

Box plots showing the differences in Johnsen’s score and MTR asymmetry in control and cisplatin-treated mice (5 animals in each group). (a) A significantly lower Johnsen’s score is seen in cisplatin-treated mice. (b) A significantly lower Cr-CEST effect is seen in cisplatin-treated testes than that in controls. *P = 0.008. Statistical analysis was performed using Mann–Whitney U test. asym, asymmetry; Cr-CEST, creatine-chemical exchange saturation transfer; MTR, magnetization transfer ratio.

Fig. 5

Correlation analysis of the Cr-CEST effect and the Johnsen’s score. A strong correlation was observed between the Cr-CEST effect and Johnsen’s score (ρ = 0.93, P < 0.001, 5 animals in each group). Cr-CEST, creatine-chemical exchange saturation transfer.