Using a rat model of spinal cord injury (SCI), diffusion tensor imaging (DTI) is compared to double diffusion encoding (DDE) at the acute and chronic stages after injury. Acute DDE measurements show a strong relationship with chronic functional outcomes whereas DTI has poor prognostic sensitivity. On the other hand, during the chronic stage, DTI outperforms DDE as a marker of functional status. The differences reflect evolving pathologies that must be considered for the appropriate application and interpretation of DTI and DDE. The results also highlight the prognostic potential of DDE in acute SCI.