Spatially regularized super-resolved constrained spherical deconvolution (SR²-CSD) of diffusion MRI data

Constrained Spherical Deconvolution (CSD) is widely used to estimate the white matter fiber orientation distribution (FOD) from diffusion MRI data. Its angular resolution depends on the maximum spherical harmonic order (l_max): low l_max yields smooth but poorly resolved FODs, while high l_max, as in Super-CSD, enables resolving fiber crossings with small inter-fiber angles but increases sensitivity to noise. In this proof-of-concept study, we introduce Spatially Regularized Super-Resolved CSD (SR²-CSD), a novel method that regularizes Super-CSD using a spatial FOD prior estimated via a self-calibrated total variation denoiser. We evaluated SR²-CSD against CSD and Super-CSD across four datasets: (i) the HARDI-2013 challenge numerical phantom, assessing angular and peak number errors across multiple signal-to-noise ratio (SNR) levels and CSD variants (single-/multi-shell, single-/multi-tissue); (ii) the Sherbrooke in vivo dataset, evaluating spatial coherence of FODs; (iii) a six-subject test-retest dataset acquired with both full (96 gradient directions) and subsampled (45 directions) protocols, assessing reproducibility; and (iv) the DiSCo phantom, evaluating tractography accuracy under varying SNR levels and multiple noise repetitions. Across all evaluations, SR²-CSD consistently reduced angular and peak number errors, improved spatial coherence, enhanced test-retest reproducibility, and yielded connectivity matrices more strongly correlated with ground-truth. Most improvements were statistically significant under multiple-comparison correction. These results demonstrate that incorporating spatial priors into CSD is feasible, mitigates estimation instability, and improves FOD reconstruction accuracy.