Time-division multiplexing (TDM) sequence removes bias in T2 estimation and relaxation-diffusion measurements.

Purpose: To compare the performance of multi-echo (ME) and time-division multiplexing (TDM) sequences for accelerated relaxation-diffusion MRI (rdMRI) acquisition and to examine their reliability in estimating accurate rdMRI microstructure measures.

Method: The ME, TDM, and the reference single-echo (SE) sequences with six echo times (TE) were implemented using Pulseq with single-band (SB-) and multi-band 2 (MB2-) acceleration factors. On a diffusion phantom, the image intensities of the three sequences were compared, and the differences were quantified using the normalized root mean squared error (NRMSE). For the in-vivo brain scan, besides the image intensity comparison and T2-estimates, different methods were used to assess sequence-related effects on microstructure estimation, including the relaxation diffusion imaging moment (REDIM) and the maximum-entropy relaxation diffusion distribution (MaxEnt-RDD).

Results: TDM performance was similar to the gold standard SE acquisition, whereas ME showed greater biases (3-4× larger NRMSEs for phantom, 2× for in-vivo). T2 values obtained from TDM closely matched SE, whereas ME sequences underestimated the T2 relaxation time. TDM provided similar diffusion and relaxation parameters as SE using REDIM, whereas SB-ME exhibited a 60% larger bias in the map and on average 3.5× larger bias in the covariance between relaxation-diffusion coefficients.

Conclusion: Our analysis demonstrates that TDM provides a more accurate estimation of relaxation-diffusion measurements while accelerating the acquisitions by a factor of 2 to 3.