Network approaches provide sensitive biomarkers for neurological conditions such as Alzheimer’s disease. Mouse models provide tools to dissect vulnerable circuits at prodromal stages, and to assess the effects of interventions. We have simulated mouse brain structural connectomes, balancing angular, spatial resolution and scan time. Specifically, we evaluated protocols with 6, 12, 15, 20, 30, 45, 60 and 120 angles; and 3 voxel sizes at 43, 86 and 172 µm. Our results indicate schemes using 46 or 60 diffusion directions, acquired at 86 µm resolution achieve a good cost/performance balance relative to a high spatial, high angular resolution sampling scheme.