Abstract While many useful microstructural indices, as well as orientation distribution functions, can be obtained from multi-shell dMRI data, there is growing interest in exploring the richer set of microstructural features that can be extracted from the full ensemble average propagator (EAP). The EAP can be readily computed from diffusion spectrum imaging (DSI) data, at the cost of a very lengthy acquisition. Compressed sensing (CS) has been used to make DSI more practical by reducing its acquisition time. CS applied to DSI (CS-DSI) attempts to reconstruct the EAP from significantly undersampled q-space data. We present a post mortem validation study where we evaluate the ability of CS-DSI to approximate not only fully sampled DSI but also multi-shell acquisitions with high fidelity. Human brain samples are imaged with high-resolution DSI at 9.4T and with polarization-sensitive optical coherence tomography (PSOCT). The latter provides direct measurements of axonal orientations at microscopic resolutions, allowing us to evaluate the mesoscopic orientation estimates obtained from diffusion MRI, in terms of their angular error and the presence of spurious peaks. We test two fast, dictionary-based, L2-regularized algorithms for CS-DSI reconstruction. We find that, for a CS acceleration factor of R=3, i.e., an acquisition with 171 gradient directions, one of these methods is able to achieve both low angular error and low number of spurious peaks. With a scan length similar to that of high angular resolution multi-shell acquisition schemes, this CS-DSI approach is able to approximate both fully sampled DSI and multi-shell data with high accuracy. Thus it is suitable for orientation reconstruction and microstructural modeling techniques that require either grid- or shell-based acquisitions. We find that the signal-to-noise ratio (SNR) of the training data used to construct the dictionary can have an impact on the accuracy of CS-DSI, but that there is substantial robustness to loss of SNR in the test data. Finally, we show that, as the CS acceleration factor increases beyond R=3, the accuracy of these reconstruction methods degrade, either in terms of the angular error, or in terms of the number of spurious peaks. Our results provide useful benchmarks for the future development of even more efficient q-space acceleration techniques.

High-fidelity approximation of grid- and shell-based sampling schemes from undersampled DSI using compressed sensing: Post mortem validation