Methods

Cell and tissue morphology

The microscopic geometry of tissue is imprinted in the sizes, shapes, and orientations of the water diffusion tensors that are measured with dMRI. Conventional methods give diffusion tensors that are averaged over all the microscopic water environments within the millimeter-size imaging voxels, thereby giving ambiguous information for heterogeneous tissue which is ubiquitous in the human brain. Here we design new types of MRI diffusion encoding that have the capability to disentangle the effects of microscopic diffusion tensor sizes, shapes, and orientations, allowing for detailed tissue characterization in terms of well-defined statistical measures of the diffusion tensor distributions. These measures have simple and intuitive relations to tissue properties such as average cell shape and variability of cell density.

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Blood capillary density

Water in tissue and flowing in the capillary network have distinctly different patterns of translational motion. Our new dMRI method relies on motion encoding with variable sensitivity to flow and diffusion to quantify the density of blood capillaries.

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Membrane permeability

The plasma membrane separates the intracellular space from the surroundings and is an efficient barrier for water. The permeability of the membrane is affected by its chemical composition and the presence of channel proteins such as aquaporins. We have developed a new dMRI method to quantify the rate of molecular exchange between microscopic tissue environments with different local water diffusivity. The exchange rate is influenced by the barrier properties of the membrane and can for simple cellular systems be converted to a quantitative measure of the membrane permeability.