The dot-compartment revealed? Diffusion MRI with ultra-strong gradients and spherical tensor encoding in the living human brain

The so-called dot-compartment is conjectured in diffusion MRI to represent small spherical spaces, such as cell bodies, in which the diffusion is restricted in all directions. Previous investigations inferred its existence from data acquired with directional diffusion encoding which does not permit a straightforward separation of signals from 'sticks' (axons) and signals from 'dots'. Here we combine isotropic diffusion encoding with ultra-strong diffusion gradients (240 mT/m) to achieve high diffusion-weightings with high signal to noise ratio, while suppressing signal arising from anisotropic water compartments with significant mobility along at least one axis (e.g., axons). A dot-compartment, defined to have apparent diffusion coefficient equal to zero and no exchange, would result in a non-decaying signal at very high b-values (b. 7000 s/mm(2)). With this unique experimental setup, a residual yet slowly decaying signal above the noise floor for b-values as high as 15000 s/mm(2) was seen clearly in the cerebellar grey matter (GM), and in several white matter (WM) regions to some extent. Upper limits of the dot-signal-fraction were estimated to be 1.8% in cerebellar GM and 0.5% in WM. By relaxing the assumption of zero diffusivity, the signal at high b-values in cerebellar GM could be represented more accurately by an isotropic water pool with a low apparent diffusivity of 0.12 mu m(2)/ms and a substantial signal fraction of 9.7%. The T2 of this component was estimated to be around 61 ms. This remaining signal at high b-values has potential to serve as a novel and simple marker for isotropically-restricted water compartments in cerebellar GM.