Oscillating gradient spin echo diffusion time effects implicate variations in neurite beading for the heterogeneous reduced diffusion in human acute ischemic stroke lesions.

Purpose: Monte Carlo simulations and short diffusion time measurements have suggested neurite beading and swelling as the underlying mechanism of reduced diffusion in acute stroke, although the observed diffusion time dependence is often heterogeneous and not yet fully understood. This study aimed to investigate the heterogeneity of diffusion time effects in ischemic lesions and explore the potential microstructural basis with Monte Carlo simulations.

Methods: Pulsed gradient spin echo (PGSE, diffusion time 40 ms) and oscillating gradient spin echo (OGSE 40 Hz, diffusion time ˜5.1 ms) were acquired within 5 min in 39 acute ischemic stroke patients at 3 T. Mean, axial, and radial diffusivity differences between OGSE and PGSE (ΔMD/ΔAD/ΔRD) were compared between lesion and contralateral tissues (white and gray matter). Monte Carlo diffusion simulations of beaded axons for the experimental waveforms were used to investigate the effects of neurite morphology on time-dependent diffusivity changes.

Results: PGSE yielded the typical mean diffusivity (MD) reduction of -40 ± 10% in ischemic lesions, whereas it was less at -29 ± 11% for OGSE 40 Hz. The OGSE-PGSE diffusion time difference was greater in lesions (ΔMD = 0.12 ± 0.06 × 10 mm/s) than contralateral white matter (ΔMD = 0.04 ± 0.06 × 10 mm/s), consistent with larger beading amplitude (0.18-0.43) and intracellular volume fraction (0.61-0.78) in lesions. ΔMD maps revealed regional variation with the largest effects in internal capsule and corona radiata.

Conclusion: This study found greater diffusion time effects in ischemic regions with purportedly larger axons. Monte Carlo simulations further support that the pronounced OGSE-PGSE diffusivity differences are expected in large axons with high beading amplitude.