PurposeTo improve the detection and subsequent estimation of the diffusion properties of strongly J-coupled metabolites in diffusion-weighted MRS (DWS).MethodsA new sequence for single-voxel diffusion-weighted 1H MR spectroscopy, named DW-SPECIAL, is proposed. It combines the semi-adiabatic SPECIAL sequence with a stimulated echo diffusion block. Acquisitions with DW-SPECIAL and STE-LASER, the current gold standard for rodent DWS experiments at high fields, were performed at 14.1T on phantoms and in vivo on the rat brain. The apparent diffusion coefficient and intra-stick diffusivity (Callaghan's model, randomly-oriented sticks) were fitted and compared between the sequences for glutamate, glutamine, myo-inositol, taurine, total NAA, total Cho, total Cr, and the macromolecules.ResultsThe shorter TE achieved with DW-SPECIAL (18 ms against 33 ms with STE-LASER) substantially limited the metabolites' signal loss caused by J-evolution. In addition, DW-SPECIAL preserved the main advantages of STE-LASER: absence of cross-terms, diffusion time during a stimulated echo, and limited sensitivity to B1 inhomogeneities. In vivo, compared to STE-LASER, DW-SPECIAL yielded the same spectral quality and reduced the Cramer Rao Lower Bounds for J-coupled metabolites, irrespective of the b-value. DW-SPECIAL also reduced the SD of the metabolites' diffusion estimates based on individual animal fitting without loss of accuracy compared to the fit on the averaged decay.ConclusionWe conclude that due to its reduced TE, DW-SPECIAL can serve as an alternative to STE-LASER when strongly J-coupled metabolites like glutamine are investigated, thereby extending the range of accessible metabolites in the context of DWS acquisitions.