Axonal T₂ estimation using the spherical variance of the strongly diffusion-weighted MRI signal

In magnetic resonance imaging, the application of a strong diffusion weighting suppresses the signal contributions from the less diffusion-restricted constituents of the brain's white matter, thus enabling the estimation of the transverse relaxation time T₂ that arises from the more diffusion-restricted constituents such as the axons. However, the presence of cell nuclei and vacuoles can confound the estimation of the axonal T₂, as diffusion within those structures is also restricted, causing the corresponding signal to survive the strong diffusion weighting. We devise an estimator of the axonal T₂ based on the directional spherical variance of the strongly diffusion-weighted signal. The spherical variance T₂ estimates are insensitive to the presence of isotropic contributions to the signal like those provided by cell nuclei and vacuoles. We show that with a strong diffusion weighting these estimates differ from those obtained using the directional spherical mean of the signal which contains both axonal and isotropically-restricted contributions. Our findings hint at the presence of an MRI-visible isotropically-restricted contribution to the signal in the white matter ex vivo fixed tissue (monkey) at 7T, and do not allow us to discard such a possibility also for in vivo human data collected with a clinical 3T system.