This chapter offers a comprehensive summary of applications of advanced diffusion encoding methods in MRI within a narrowly defined area of in vivo human measurements with imaging read-out and voxel-by-voxel data analysis. The list of methods comprises tensor-valued encoding to investigate cell densities, shapes, and orientations in heterogeneous tissues, time/frequency-dependent encoding for estimating structural length scales, adjustable velocity-encoding to monitor flow in the microcapillary network, double encoding with varying mixing times to assess diffusional exchange between distinct tissue microenvironments and across cell membranes, and relaxation–diffusion correlation to resolve and separately characterize tissue microenvironments in terms of their local chemical composition and microstructure. The shown examples include proof-of-concept measurements on healthy volunteers, pilot investigations of pathologies, and clinical research involving 10–100 subjects. Studied organs include brain, breast, prostate, liver, kidney, placenta, muscle, and peripheral nerve, with examples of pathologies from tumors, schizophrenia, multiple sclerosis, stroke, neurocysticercosis, pre-eclampsia, and chronic exertional compartment syndrome.
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