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

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.