Positional brain shift (PBS), the sagging of the brain under the effect of gravity, is comparable in magnitude to the margin of error for the success of stereotactic interventions (∼1 mm). This non-uniform shift due to slight differences in head orientation can lead to a significant discrepancy between the planned and the actual location of surgical targets. Accurate in vivo measurements of this complex deformation are critical for the design and validation of an appropriate compensation to integrate into neuronavigational systems. PBS arising from prone-to-supine change of head orientation was measured with magnetic resonance imaging on 11 young adults. The full-field displacement was extracted on a voxel-basis via digital volume correlation and analysed in a standard reference space. Results showed the need for target-specific correction of surgical targets, as a significant displacement ranging from 0.52 mm to 0.77 mm was measured at surgically relevant structures. Strain analysis further revealed local variability in compressibility: anterior regions showed expansion (both volume and shape change), whereas posterior regions showed small compression, mostly dominated by shape change. Finally, analysis of correlation demonstrated the potential for further patient-and intervention-specific adjustments, as intra-cranial breadth and head tilt correlated with PBS reaching statistical significance.