From Brownian motion to virtual biopsy: a historical perspective from 40 years of diffusion MRI

Diffusion MRI was introduced in 1985, showing how the diffusive motion of molecules, especially water, could be spatially encoded with MRI to produce images revealing the underlying structure of biologic tissues at a microscopic scale. Diffusion is one of several Intravoxel Incoherent Motions (IVIM) accessible to MRI together with blood microcirculation. Diffusion imaging first revolutionized the management of acute cerebral ischemia by allowing diagnosis at an acute stage when therapies can still work, saving the outcomes of many patients. Since then, the field of diffusion imaging has expanded to the whole body, with broad applications in both clinical and research settings, providing insights into tissue integrity, structural and functional abnormalities from the hindered diffusive movement of water molecules in tissues. Diffusion imaging is particularly used to manage many neurologic disorders and in oncology for detecting and classifying cancer lesions, as well as monitoring treatment response at an early stage. The second major impact of diffusion imaging concerns the wiring of the brain (Diffusion Tensor Imaging, DTI), allowing to obtain from the anisotropic movement of water molecules in the brain white-matter images in 3 dimensions of the brain connections making up the Connectome. DTI has opened up new avenues of clinical diagnosis and research to investigate brain diseases, neurogenesis and aging, with a rapidly extending field of application in psychiatry, revealing how mental illnesses could be seen as Connectome spacetime disorders. Adding that water diffusion is closely associated to neuronal activity, as shown from diffusion fMRI, one may consider that diffusion MRI is ideally suited to investigate both brain structure and function. This article retraces the early days and milestones of diffusion MRI which spawned over 40 years, showing how diffusion MRI emerged and expanded in the research and clinical fields, up to become a pillar of modern clinical imaging.