Characterization of microstructures in live tissues is one of the keys to diagnosing early stages of pathology and understanding disease mechanisms. However, the extraction of reliable information on biomarkers based on microstructure details is still a challenge, as the size of features that can be resolved with non-invasive Magnetic Resonance Imaging (MRI) is orders of magnitude larger than the relevant structures. Here we derive from quantum information theory the ultimate precision limits for obtaining such details by MRI probing of water-molecule diffusion. We show that already available MRI pulse sequences can be optimized to attain the ultimate precision limits by choosing control parameters that are uniquely determined by the expected size, the diffusion coefficient and the spin relaxation time $T_{2}$. By attaining the ultimate precision limit per measurement, the number of measurements and the total acquisition time may be drastically reduced compared to the present state of the art. These results will therefore allow MRI to advance towards unravelling a wealth of diagnostic information.