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

The dependence of the diffusion MRI signal on the diffusion time carries signatures of restricted diffusion and exchange. Here we seek to highlight these signatures in the human brain by performing experiments using free gradient waveforms designed to be selectively sensitive to the two effects. We examine six healthy volunteers using both strong and ultra-strong gradients (80, 200 and 300 mT/m). In an experiment featuring a large set of 150 gradient waveforms with different sensitivities to restricted diffusion and exchange, our results reveal unique and different time-dependence signatures in grey and white matter. Grey matter was characterised by both restricted diffusion and exchange and white matter predominantly by restricted diffusion. Exchange in grey matter was at least twice as fast as in white matter, across all subjects and all gradient strengths. The cerebellar cortex featured relatively short exchange times (115 ms). Furthermore, we show that gradient waveforms with tailored designs can be used to map exchange in the human brain. We also assessed the feasibility of clinical applications of the method used in this work and found that the exchange-related contrast obtained with a 25-minute protocol at 300 mT/m was preserved in a 4-minute protocol at 300 mT/m and a 10-minute protocol at 80 mT/m. Our work underlines the utility of free waveforms for detecting time dependence signatures due to restricted diffusion and exchange in vivo, which may potentially serve as a tool for studying diseased tissue.