Field-to-susceptibility inversion in quantitative susceptibility mapping (QSM) is ill-posed and needs numerical stabilization through either regularization or oversampling by acquiring data at three or more object orientations. Calculation Of Susceptibility through Multiple Orientations Sampling (COSMOS) is an established oversampling approach and regarded as QSM gold standard. It achieves a well-conditioned inverse problem, requiring rotations by 0 • , 60 • and 120 • in the yz-plane. However, this is impractical in vivo, where head rotations are typically restricted to a range of ±25 • . Non-ideal sampling degrades the conditioning with residual streaking artifacts whose mitigation needs further regularization. Moreover, susceptibility anisotropy in white matter is not considered in the COSMOS model, which may introduce additional bias. The current work presents a thorough investigation of these effects in primate brain.

Methods: Gradient-recalled echo (GRE) data of an entire fixed chimpanzee brain were acquired at 7 T (350 μm resolution, 10 orientations) including ideal COSMOS sampling and realistic rotations in vivo. Comparisons of the results included ideal COSMOS, in-vivo feasible acquisitions with 3-8 orientations and single-orientation iLSQR QSM. Results: In-vivo feasible and optimal COSMOS yielded high-quality susceptibility maps with increased SNR resulting from averaging multiple acquisitions. COSMOS reconstructions from non-ideal rotations about a single axis required additional L2-regularization to mitigate residual streaking artifacts. Conclusion: In view of unconsidered anisotropy effects, added complexity of the reconstruction, and the general challenge of multi-orientation acquisitions, advantages of sub-optimal COSMOS schemes over regularized singleorientation QSM appear limited in in-vivo settings.