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The dependence of the diffusion MRI signal on the diffusion time carriessignatures of restricted diffusion and exchange. Here we seek to highlightthese signatures in the human brain by performing experiments using freegradient waveforms that are selectively sensitive to the two effects. Weexamine six healthy volunteers using both strong and ultra-strong gradients(80, 200 and 300 mT/m). In an experiment featuring a large set of gradientwaveforms with different sensitivities to restricted diffusion and exchange(150 samples), our results reveal unique time-dependence signatures in grey andwhite matter, where the former is characterised by both restricted diffusionand exchange and the latter predominantly exhibits restricted diffusion.Furthermore, we show that gradient waveforms with independently varyingsensitivities to restricted diffusion and exchange can be used to map exchangein the human brain. We consistently find that exchange in grey matter is atleast twice as fast as in white matter, across all subjects and all gradientstrengths. The shortest exchange times observed in this study were in thecerebellar cortex (115 ms). We also assess the feasibility of future clinicalapplications of the method used in this work, where we find that the grey-whitematter exchange contrast obtained with a 25-minute 300 mT/m protocol ispreserved by a 4-minute 300 mT/m and a 10-minute 80 mT/m protocol. Our workunderlines the utility of free waveforms for detecting time-dependencesignatures due to restricted diffusion and exchange in vivo, which maypotentially serve as a tool for studying diseased tissue.

Diffusion MRI with free gradient waveforms on a high-performance gradient system: Probing restriction and exchange in the human brain