ABSTRACT Purpose Oscillating‐gradient spin‐echo (OGSE) diffusion MRI probes cell geometry and membrane integrity through the frequency‐dependence of kurtosis, but prior studies have reported inconsistent findings depending on how frequency is varied. We compared frequency‐dependent kurtosis in the human brain under two regimes: varying frequency with fixed total waveform duration (fixed‐) or number of oscillations (fixed‐). Methods Eleven healthy volunteers were scanned on the 3 T Connectome 2.0 system with OGSE using 500 mT/m gradients. Mean kurtosis (MK) was measured using three fixed‐ waveforms ( ≈ 80 ms) and four fixed‐ waveforms ( = 1). The adiabatic Kärger exchange model was fit to MK in 48 white matter (WM) and 70 gray matter (GM) regions, yielding estimates of water exchange time (), intracellular fraction (), extracellular tortuosity (), and asymptotic kurtosis (). Results Distinct frequency‐dependence was observed between regimes. In fixed‐, MK decreased with frequency in both WM and GM, reflecting diffusion coarse‐graining from structural disorder. In fixed‐, MK increased with frequency in GM but was relatively flat in WM, indicating greater sensitivity to exchange. Parameter estimates showed biologically meaningful contrasts: WM exhibited longer , higher , and greater , consistent with tightly packed, myelinated axons and anisotropic extracellular space. GM showed shorter and higher , reflecting greater heterogeneity and CSF partial volume. Conclusion Fixed‐ and fixed‐ OGSE provide complementary sensitivity to microstructural features. Fixed‐ emphasizes structural disorder, while fixed‐ highlights membrane permeability and exchange. The extended frequency regimes enabled by ultra‐strong gradients advance OGSE as a powerful tool for probing human brain tissue microstructure.
Sung et al. (Sun,) studied this question.
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