Magnetic resonance in medicine · 2026
Complementary Sensitivity of Fixed-Time and Fixed-Oscillation Regimes to Exchange and Structural Disorder in the Human Brain Revealed Using Oscillating-Gradient Diffusion MRI With Ultra-Strong Gradients.
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Sung Dongsuk, Chan Kwok-Shing, Gerold Julianna, Zhong Wen, Zheng Jialan, Tian Qiyuan, Guo Hua, Huang Susie Y, Lee Hong-Hsi
Аннотация
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- T ) or number of oscillations (fixed- N ).
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- T waveforms ( T ≈ 80 ms) and four fixed- N waveforms ( N = 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 ( t ex ), intracellular fraction ( f ic ), extracellular tortuosity ( α D ), and asymptotic kurtosis ( K ∞ ).
RESULTS: Distinct frequency-dependence was observed between regimes. In fixed- T , MK decreased with frequency in both WM and GM, reflecting diffusion coarse-graining from structural disorder. In fixed- N , 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 t ex , higher f ic , and greater α D , consistent with tightly packed, myelinated axons and anisotropic extracellular space. GM showed shorter t ex and higher K ∞ , reflecting greater heterogeneity and CSF partial volume.
CONCLUSION: Fixed- T and fixed- N OGSE provide complementary sensitivity to microstructural features. Fixed- T emphasizes structural disorder, while fixed- N 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.
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- T waveforms ( T ≈ 80 ms) and four fixed- N waveforms ( N = 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 ( t ex ), intracellular fraction ( f ic ), extracellular tortuosity ( α D ), and asymptotic kurtosis ( K ∞ ).
RESULTS: Distinct frequency-dependence was observed between regimes. In fixed- T , MK decreased with frequency in both WM and GM, reflecting diffusion coarse-graining from structural disorder. In fixed- N , 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 t ex , higher f ic , and greater α D , consistent with tightly packed, myelinated axons and anisotropic extracellular space. GM showed shorter t ex and higher K ∞ , reflecting greater heterogeneity and CSF partial volume.
CONCLUSION: Fixed- T and fixed- N OGSE provide complementary sensitivity to microstructural features. Fixed- T emphasizes structural disorder, while fixed- N 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.