Mapping grey and white matter activity in the human brain with isotropic ADC-fMRI

Functional MRI (fMRI) using the blood-oxygen level dependent (BOLD) signal provides valuable insight into grey matter activity. However, uncertainty surrounds the white matter BOLD signal. Apparent diffusion coefficient (ADC) offers an alternative fMRI contrast sensitive to transient cellular deformations during neural activity, facilitating detection of both grey and white matter activity. Further, through minimising vascular contamination, ADC-fMRI has the potential to overcome the limited temporal specificity of the BOLD signal. However, the use of linear diffusion encoding introduces sensitivity to fibre directionality, while averaging over multiple directions comes at great cost to temporal resolution. In this study, we used spherical b-tensor encoding to impart diffusion sensitisation in all directions per shot, providing an ADC-fMRI contrast capable of detecting activity independently of fibre directionality. We provide evidence from two task-based experiments on a clinical scanner that isotropic ADC-fMRI is more temporally specific than BOLD-fMRI, and offers more balanced mapping of grey and white matter activity. We further demonstrate that isotropic ADC-fMRI detects white matter activity independently of fibre direction, while linear ADC-fMRI preferentially detects activity in voxels containing fibres perpendicular to the diffusion encoding direction. Thus, isotropic ADC-fMRI opens avenues for investigation into whole-brain grey and white matter functional connectivity.