A modelling and experimental framework to investigate the sensitivity of steady-state diffusion MRI to microstructure

Motivation: Diffusion-weighted steady-state free precession (DW-SSFP) has demonstrated higher SNR-efficiency vs the diffusion-weighted spin-echo (DW-SE) in post-mortem tissue. However, its sensitivity to microstructural features has not been comprehensively investigated. Goal(s): To develop an investigation framework to quantify DW-SSFP’s sensitivity to microstructure. Approach: We combined Monte-Carlo simulations with phantom experiments incorporating diffusion hinderance/restriction and an ex-vivo mouse brain, comparing the estimated diffusion attenuation of DW-SSFP vs a DW-SE sequence with matched gradient waveforms and diffusion timings. Results: DW-SSFP exhibited higher diffusion attenuation vs DW-SE in all tested substrates when gradient waveforms/timings are matched, suggesting its unique signal forming mechanisms may be highly sensitive to microstructure. Impact: We present a framework combining Monte-Carlo simulations with experiments to characterise the sensitivity of diffusion-weighted steady-state free precession (DW-SSFP) to microstructure. DW-SSFP demonstrates greater signal attenuation versus a gradient waveform/timing-matched DW-SE across different substrates, demonstrating its potential for microstructural imaging.