Significance Imaging provides an insight into biological patho-mechanisms of diseases. However, the link between the imaging phenotype and the underlying molecular processes is often not well understood. Methods such as metabolomics and proteomics reveal detailed information about these processes. Unfortunately, they provide no spatial information and thus cannot be easily correlated with functional imaging. We have developed an image-guided milling machine and unique workflows to precisely isolate tissue samples based on imaging data. The tissue samples remain cooled during the entire procedure, preventing sample degradation. This enables us to correlate, at an unprecedented spatial precision, comprehensive imaging information with metabolomics and proteomics data, leading to a better understanding of diseases.