Diffusion MRI is an exquisitely sensitive probe of tissue microstructure, and is currently the only non-invasive measure of the brain's fibre architecture. As this technique becomes more sophisticated and microstructurally informative, there is increasing value in comparing diffusion MRI with microscopic imaging in the same tissue samples. This study compared estimates of fibre orientation dispersion in white matter derived from diffusion MRI to reference measures of dispersion obtained from polarized light imaging and histology.Three post-mortem brain specimens were scanned with diffusion MRI and analyzed with a two-compartment dispersion model. The specimens were then sectioned for microscopy, including polarized light imaging estimates of fibre orientation and histological quantitative estimates of myelin and astrocytes. Dispersion estimates were correlated on region – and voxel-wise levels in the corpus callosum, the centrum semiovale and the corticospinal tract.The region-wise analysis yielded correlation coefficients of r = 0.79 for the diffusion MRI and histology comparison, while r = 0.60 was reported for the comparison with polarized light imaging. In the corpus callosum, we observed a pattern of higher dispersion at the midline compared to its lateral aspects. This pattern was present in all modalities and the dispersion profiles from microscopy and diffusion MRI were highly correlated. The astrocytes appeared to have minor contribution to dispersion observed with diffusion MRI.These results demonstrate that fibre orientation dispersion estimates from diffusion MRI represents the tissue architecture well. Dispersion models might be improved by more faithfully incorporating an informed mapping based on microscopy data.

One of the most prominent characteristics of the human neocortex is its laminated structure. The first person to observe this was Francesco Gennari in the second half the 18th century: in the middle of the depth of primary visual cortex, myelinated fibres are so abundant that he could observe them with bare eyes as a white line. Because of its saliency, the stria of Gennari has a rich history in cyto- and myeloarchitectural research as well as in magnetic resonance (MR) microscopy. In the present paper we show for the first time the layered structure of the human neocortex with ex vivo diffusion weighted imaging (DWI). To achieve the necessary spatial and angular resolution, primary visual cortex samples were scanned on an 11.7 T small-animal MR system to characterize the diffusion properties of the cortical laminae and the stria of Gennari in particular. The results demonstrated that fractional anisotropy varied over cortical depth, showing reduced anisotropy in the stria of Gennari, the inner band of Baillarger and the deepest layer of the cortex. Orientation density functions showed multiple components in the stria of Gennari and deeper layers of the cortex. Potential applications of layer-specific diffusion imaging include characterization of clinical abnormalities, cortical mapping and (intra)cortical tractography. We conclude that future high-resolution in vivo cortical DWI investigations should take into account the layer-specificity of the diffusion properties.

Purpose: To investigate the effect of realistic microstructural geometry on the susceptibility-weighted MR signal in white matter (WM), with application to demyelination. Methods: Previous work has modeled susceptibility-weighted signals under the assumption that axons are cylindrical. In this study, we explored the implications of this assumption by considering the effect of more realistic geometries. A threecompartment WM model incorporating relevant properties based on the literature was used to predict the MR signal. Myelinated axons were modeled with several cross-sectional geometries of increasing realism: nested circles, warped/elliptical circles, and measured axonal geometries from electron micrographs. Signal simulations from the different microstructural geometries were compared with measured signals from a cuprizone mouse model with varying degrees of demyelination. Results: Simulation results suggest that axonal geometry affects the MR signal. Predictions with realistic models were significantly different compared with circular models under the same microstructural tissue properties, for simulations with and without diffusion. Conclusion: The geometry of axons affects the MR signal significantly. Literature estimates of myelin susceptibility, which are based on fitting biophysical models to the MR signal, are likely to be biased by the assumed geometry, as will any derived microstructural properties. Magn Reson Med 79:489-500, 2018. V C 2017 International Society for Magnetic Resonance in Medicine.