Scaling temporal resolution from mice to humans: Challenges and innovations in preclinical imaging of translational models

Temporal scaling physiology differs significantly between mice and humans, essentially because, in mice, several biological processes occur at a much faster time scale. Mice have faster metabolism, heart and respiratory rate, blood flow rates, brain activity, and disease progression dynamics. By combining three-dimensional spatial data with time, four-dimensional imaging enables to capture rapid, transient physiological events and long-term pathogenetic changes in living mouse models, enhancing the translation of biological insights to human disease processes. In preclinical imaging, technical trade-offs among spatial and temporal resolution and field of view coexist with the need for anaesthesia or restraints to prevent motion, as well as invasive procedures to access and visualize target structures, potentially affecting physiology and animal welfare. These issues are addressed by developing specialized and advanced imaging technologies, applicable to awake or freely moving rodents, and through careful animal management using a multidisciplinary approach, opening new horizons in the study of human diseases in mouse models. Combining different techniques or using advanced algorithms can further help overcome the limitations of individual imaging modalities and improve both spatial and temporal resolution. We provide an overview of emerging preclinical imaging techniques that improve the translation of findings from mouse models, advancing our understanding of human disease physiology and pathogenesis through enhanced spatiotemporal resolution. It aims to help researchers critically select complementary experimental methods across diverse scientific fields, at the same time as summarizing recent technological advances in preclinical imaging and key considerations in animal care and use.