Noninvasive Dual-Modality Photoacoustic-Ultrasonic Imaging to Detect Mammalian Embryo Abnormalities after Prenatal Exposure to Methylmercury Chloride (MMC): A Mouse Study

BACKGROUND: Severe environmental pollution and contaminants left in the environment due to the abuse of chemicals, such as methylmercury, arc associated with an increasing number of embryonic disorders. Ultrasound imaging has been widely used to investigate embryonic development malformation and dysorganoplasia in both research and clinics. However, this technique is limited by its low contrast and lacking functional parameters such as the ability to measure blood oxygen saturation (Sa02) and hemoglobin content (HbT) in tissues, measures that could be early vital indicators for embryonic development abnormality. Herein, we proposed combining two highly complementary techniques into a photoacoustic-ultrasound (PA-US) dual-modality imaging approach to noninvasively detect early mouse embryo abnormalities caused by methylmercury chloride (MMC) in real time. OBJECTIVES: This study aimed to assess the use of PA-US dual-modality imaging for noninvasive detection of embryonic toxicity at different stages of growth following prenatal MMC exposure. Additionally, we compared the PA-US imagining results to traditional histological methods to determine whether this noninvasive method could detect early developmental defects in utero. METHODS: Different dosages of MMC were administrated to pregnant mice by gavage to establish models of different levels of embryonic malformation. Ultrasound, photoacoustic signal intensity (PSI), blood oxygen saturation (SaO(2)), and hemoglobin content (HbT) were quantified in all experimental groups. Furthermore, the embryos were sectioned and examined for pathological changes. RESULTS: Using PA-US imaging, we detected differences in PSI, SaO(2), HbT, and heart volume at embryonic day (E)14.5 and E11.5 for low and high dosages of MMC, respectively. More important, our results showed that differences between control and treated embryos identified by in utero PAUS imaging were consistent with those identified in ex vivo embryos using histological methods. CONCLUSION: Our results suggest that noninvasive dual-modality PA-US is a promising strategy for detecting developmental toxicology in the uterus. Overall, this study presents a new approach for detecting embryonic toxicities, which could be crucial in clinics when diagnosing aberrant embryonic development.