  Purpose: Oscillating gradient spin-echo (OGSE) diffusion MRI provides
information about the microstructure of biological tissues via the frequency
dependence of the apparent diffusion coefficient (ADC). ADC dependence on OGSE
frequency has been explored in numerous rodent studies, but applications in the
human brain have been limited and have suffered from low contrast between
different frequencies, long scan times and a limited exploration of the nature
of the ADC dependence on frequency. Methods: Multiple frequency OGSE
acquisitions were acquired in healthy subjects at 7 T to explore the power-law
frequency dependence of ADC, the "diffusion dispersion". Further, a method for
optimizing the estimation of the ADC difference between different OGSE
frequencies was developed, which enabled the design of a highly efficient
protocol for mapping diffusion dispersion. Results: For the first time,
evidence of a linear dependence of ADC on the square root of frequency in
healthy human white matter was obtained. Using the optimized protocol, high
quality, full-brain maps of apparent diffusion dispersion rate were also
demonstrated at an isotropic resolution of 2 mm in a scan time of 6 minutes.
Conclusion: This work sheds light on the nature of diffusion dispersion in the
healthy human brain and introduces full brain diffusion dispersion mapping at
clinically relevant scan times. These advances may lead to new biomarkers of
pathology or improved microstructural modelling.
