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bioRxiv · 10.1101/2022.08.17.504248

Development of a non-invasive method for testicular toxicity evaluation using a novel compact magnetic resonance imaging system

Yokota, S.·Miyaso, H.·Hirai, T.·Suga, K.·Wakayama, T.·Taquahashi, Y.·Kitajima, S.
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Abstract

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 x 0.23 x 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.

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Yokota, S., Miyaso, H., Hirai, T., Suga, K., Wakayama, T., Taquahashi, Y., Kitajima, S.. 2022-08-17. Development of a non-invasive method for testicular toxicity evaluation using a novel compact magnetic resonance imaging system. https://doi.org/10.1101/2022.08.17.504248

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