In non-clinical animal studies for drug discovery, histopathological evaluation is the most powerful tool to assess testicular toxicity. However, histological analysis is extremely invasive; many experimental animals are needed to evaluate changes in the pathology and anatomy of the testes over time. As an alternative, small animal magnetic resonance imaging (MRI) offers a non-invasive methodology to examine testicular toxicity without radiation. The present study demonstrated the suitability of a new, ready-to-use compact MRI platform using a high-field permanent magnet to assist with the evaluation of testicular toxicity. To validate the utility of the MRI platform, male mice were treated with busulfan (40 mg/kg, intraperitoneal injection). Tenty-eight days after treatment, both testes in busulfan-treated and control mice (n = 3/group) were non-invasively scanned in situ by MRI at 1 tesla. On a T1-weighted, 3D gradient-echo MRI sequences (voxel size: 0.23 × 0.23 × 0.50 mm), the total testicular volume in busulfan-treated mice was significantly smaller than in controls. On T1-weighted images, the signal intensity of the testes was significantly higher in busulfan-treated mice than in controls. The mice were sacrificed, and the testes were isolated for histopathological analysis. The weight of the testes in busulfan-treated mice significantly decreased, similar to the results of the non-invasive analysis. Additionally, periodic acid-Schiff stain–positive effusions were observed in the interstitium of the busulfan-treated mouse testes, potentially explaining T1 shortening due to a high concentration of glycoproteinaceous content. The present data demonstrated a rapid evaluation of testicular toxicity in vivo by compact MRI.

中文翻译：

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使用新型紧凑型磁共振成像系统开发一种非侵入性睾丸毒性评估方法

在药物发现的非临床动物研究中，组织病理学评估是评估睾丸毒性的最有力工具。然而，组织学分析极具侵入性。需要许多实验动物来评估睾丸的病理和解剖结构随时间的变化。作为替代方案，小动物磁共振成像 (MRI) 提供了一种非侵入性方法来检查无辐射的睾丸毒性。本研究证明了一种新的、即用型紧凑型 MRI 平台的适用性，该平台使用高场永磁体来协助评估睾丸毒性。为了验证 MRI 平台的效用，雄性小鼠接受了白消安（40 mg/kg，腹腔注射）治疗。治疗后的第十八天，白消安治疗和对照小鼠（n = 3/组）的两个睾丸均通过 1 特斯拉的 MRI 进行非侵入性原位扫描。在 T1 加权 3D 梯度回波 MRI 序列（体素大小：0.23 × 0.23 × 0.50 mm）上，白消安治疗小鼠的总睾丸体积明显小于对照组。在 T1 加权图像上，白消安治疗小鼠的睾丸信号强度显着高于对照组。处死小鼠，分离睾丸进行组织病理学分析。白消安治疗小鼠的睾丸重量显着下降，与非侵入性分析的结果相似。此外，在白消安处理的小鼠睾丸间质中观察到高碘酸-席夫染色阳性积液，可能解释由于高浓度的糖蛋白含量导致的 T1 缩短。目前的数据证明了通过紧凑型 MRI 对体内睾丸毒性的快速评估。