Understanding of the normal and diseased brain crucially depends on reliable knowledge of its microstructure. Important functions are mediated by small cortical units (columns) and even small changes in the microstructure can cause debilitating diseases. So far, this microstructure can only be determined using invasive methods such as, e.g., ex-vivo histology. This limits neuroscience, clinical research and diagnosis.My research vision is to develop novel methods for high-resolution magnetic resonance imaging (MRI) at 3T-9.4T to reliably characterize and quantify the detailed microstructure of the human cortex.This MRI-based histology will be used to investigate the cortical microstructure in health and focal cortical degeneration. Structure-function relationships in visual cortex will be elucidated in-vivo, particularly, ocular dominance columns and stripes. Specific microstructural changes in focal cortical degeneration due to Alzheimer’s disease and monocular blindness will be determined, including amyloid plaque imaging.To resolve the subtle structures and disease related changes, which have not previously been delineated in-vivo by anatomical MRI, unprecedented isotropic imaging resolution of up to 250 µm is essential. Methods for high-resolution myelin and iron mapping will be developed from novel quantitative MRI approaches that I have previously established. Super-resolution diffusion and susceptibility imaging will be developed to capture the neuropil microstructure. Anatomical imaging will be complemented by advanced high-resolution functional MRI. The multi-modal MRI data will be integrated into a unified model of MRI contrasts, cortical anatomy and tissue microstructure.My ambitious goal of developing in vivo MRI-based histology can only be achieved by an integrative approach combining innovations in MR physics, modelling and tailored (clinical) neuroscience experiments. If successful, the project will transform research and clinical imaging.