Diffusion tensor (DT) imaging and related multifiber reconstruction algorithms allow the study of in vivo microstructure and, by means of tractography, structural connectivity. Although reconstruction algorithms are promising imaging tools, high-quality diffusion-weighted imaging (DWI) datasets for verification and validation of postprocessing and analysis methods are lacking. Clinical in vivo DWI is limited by, for example, physiological noise and low signal-to-noise ratio. Here, we performed a series of DWI measurements on postmortem pig brains, which resemble the human brain in neuroanatomical complexity, to establish an ex vivo imaging pipeline for generating high-quality DWI datasets. Perfusion fixation ensured that tissue characteristics were comparable to in vivo conditions. There were three main results: (i) heat conduction and unstable tissue mechanics accounted for time-varying artefacts in the DWI dataset, which were present for up to 15 h after positioning brain tissue in the scanner; (ii) using fitted DT, q-ball, and persistent angular structure magnetic resonance imaging algorithms, any b-value between ∼2,000 and ∼8,000 s/mm(2) , with an optimal value around 4,000 s/mm(2) , allowed for consistent reconstruction of fiber directions; (iii) diffusivity measures in the postmortem brain tissue were stable over a 3-year period. On the basis of these results, we established an optimized ex vivo pipeline for high-quality and high-resolution DWI. The pipeline produces DWI data sets with a high level of tissue structure detail showing for example two parallel horizontal rims in the cerebral cortex and multiple rims in the hippocampus. We conclude that high-quality ex vivo DWI can be used to validate fiber reconstruction algorithms and to complement histological studies.

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Background and Purpose-There is growing evidence that white matter hyperintensities (WMH) should not be considered as benign age-dependent changes on MR images but indicate pathological changes with clinical consequences. Previous studies comparing subjects with WMH to normal controls have reported global reductions in cerebral blood flow (CBF) and cerebral vascular reactivity. In this study, we examined localized hemodynamic status to compare WMH to normal appearing white matter (NAWM). Methods-A group of 21 normal 85-year-old subjects were studied using dynamic contrast-enhanced MRI together with administration of acetazolamide. From a combination of anatomic images with different signal weighting, regions of interest were generated corresponding to gray and white matter and WMH. Localized measurements of CBF and cerebral blood volume (CBV) and mean transit time were obtained directly within WMH and NAWM. Results-When comparing WMH to NAWM, measurements showed significantly lower CBF (Pϭ0.004) and longer mean transit time (PϽ0.001) in WMH but no significant difference in CBV (Pϭ0.846). The increases in CBF and CBV induced by acetazolamide were significantly smaller in WMH than in NAWM (Pϭ0.026, PϽ0.001). Conclusion-These results show that a change in the hemodynamic status is present within the WMH, making these areas more likely to be exposed to transient ischemia inducing myelin rarefaction. In the future, MRI may be used to examine the effect of therapeutic strategies designed to prevent or normalize vascular changes.