Differential sensitivity of in vivo and ex vivo diffusion tensor imaging to evolving optic nerve injury in mice with retinal ischemia

Decreased axial (λ_||) and increased radial (λ_⊥) diffusivity have been shown to reflect axonal and myelin injury respectively. In the present study, evolving white matter injury within the optic nerves of mice with retinal ischemia was examined by in vivo and ex vivo measurements of λ_|| and λ_⊥. The results show that at 3 days after retinal ischemia, a 33% decrease in vivo and a 38% decrease ex vivo in λ_|| without change in λ_⊥ was observed in the injured optic nerve compared to the control, suggestive of axonal damage without myelin injury. At 14 days, both in vivo and ex vivo measured λ_⊥ increased significantly to 220-240% of the control level in the injured optic nerve suggestive of myelin damage. In contrast, the axonal injury that was clearly detected in vivo as a significantly decreased λ_|| (33% decrease) was not as clearly detected by ex vivo λ_|| (17% decrease). The current findings suggest that ex vivo λ_⊥ is comparable to in vivo λ_⊥ in detecting myelin injury. However, the structural changes resulting from axonal damage causing the decreased in vivo λ_|| may not be preserved ex vivo in the fixed tissues. Despite the accurate depiction of the pathology using λ_|| and λ_⊥ in vivo, the use of ex vivo λ_|| to extrapolate the status of axonal injury in vivo would require further investigation.