The present and the future of microstructure MRI: From a paradigm shift to normal science

The aspiration of imaging tissue microstructure with MRI is to uncover micrometer-scale tissue features within millimeter-scale imaging voxels, in vivo. This kind of super-resolution has fueled a paradigm shift within the biomedical imaging community. However, what feels like an ongoing revolution in MRI, has been conceptually experienced in physics decades ago; from this point of view, our current developments can be seen as Thomas Kuhn's "normal science" stage of progress. While the concept of model-based quantification below the nominal imaging resolution is not new, its possibilities in neuroscience and neuroradiology are only beginning to be widely appreciated. This disconnect calls for communicating the progress of tissue microstructure MR imaging to its potential users. Here, a number of recent research developments are outlined in terms of the overarching concept of coarse-graining the tissue structure over an increasing diffusion length. A variety of diffusion models and phenomena are summarized on the phase diagram of diffusion MRI, with the unresolved problems and future directions corresponding to its unexplored domains.