Rat Brain Global Ischemia–Induced Diffusion Changes Revisited: Biophysical Modeling of the Water and NAA MR “Diffusion Signal”

Purpose: To assess changes in intracellular diffusion as a mechanism for the reduction in water ADC that accompanies brain injury. Using NAA as a marker of neuronal cytoplasmic diffusion, NAA diffusion was measured before and after global ischemia (immediately postmortem) in the female Sprague–Dawley rat. Methods: Diffusion-weighted PRESS spectra, with diffusion encoding in a single direction, were acquired from large voxels of rat brain gray matter in vivo and postischemia employing either pairs of pulsed half-sine–shaped gradients (in vivo and postischemia, b_max = 19 ms/μm²) or sinusoidal oscillating gradients (in vivo only) with frequencies of 99.2–250 Hz. A 2D randomly oriented cylinder (neurite) model gave estimates of longitudinal and transverse diffusivities (D_L and D_T, respectively). In this model, D_L represents the “free” diffusivity of NAA, whereas D_T reflects highly restricted diffusion. Using oscillating gradients, the frequency dependence of D_T [D_T(ω)] gave estimates of the cylinder (axon/dendrite) radius. Results: A 10% decrease in D_L,NAA followed global ischemia, dropping from 0.391 ± 0.012 μm²/ms to 0.350 ± 0.009 μm²/ms. Modeling D_T,NAA(ω) provided an estimate of the neurite radius of 1.0 ± 0.6 μm. Conclusion: Whereas the increase in apparent intraneuronal viscosity suggested by changes in D_L,NAA may contribute to the overall reduction in water ADC associated with brain injury, it is not sufficient to be the sole explanation. Estimates of neurite radius based on D_T(ω) were consistent with literature values.