While MRI contrast agents such as those based on Gadolinium are needed to enhance the detection of structural and functional brain lesions, there are rising concerns over their safety. Here, we hypothesize that a deep learning model, trained using quantitative steady-state contrast-enhanced MRI datasets in mice and humans, could generate contrast-equivalent information from a single non-contrast MRI scan. The model was first trained, optimized, and validated in mice. It was then transferred and adapted to human data, and we find that it can substitute Gadolinium-based contrast agents for detecting functional lesions caused by aging, Schizophrenia, or Alzheimer’s disease, and, for enhancing structural lesions caused by brain or breast tumors. Since derived from a commonly-acquired MRI, this framework has the potential for broad clinical utility and can be applied retrospectively to research scans across a host of diseases.