A high-content imaging system includes a stage, a controller, a machine learning system, and an image generator. The controller receives a request including an output imaging configuration and in response the controller: (1) selects a training model associated with the output imaging configuration, (2) determines an input imaging configuration associated with the training model, and (3) configures the high-content imaging system in accordance with the input imaging configuration. The machine learning system is configured using the training model so when the machine learning system is presented with an image acquired using the input imaging configuration, the machine learning system generates an output image in accordance with the output imaging configuration. The image generator generates an image of a sample on the stage and provides the generated image to the machine learning system and, in response, the machine learning system generates an output image in accordance with the output imaging configuration.