High‐resolution, volumetric diffusion‐weighted MR spectroscopic imaging of the brain

ABSTRACT Purpose To achieve high‐resolution, three‐dimensional (3D) quantitative diffusion‐weighted MR spectroscopic imaging (DW‐MRSI) for molecule‐specific microstructural imaging of the brain. Methods We introduced and integrated several innovative acquisition and processing strategies for DW‐MRSI: (a) a new double‐spin‐echo sequence combining selective excitation, bipolar diffusion encoding, rapid spatiospectral sampling, interleaved water spectroscopic imaging data, and a special sparsely sampled echo‐volume‐imaging (EVI)‐based navigator, (b) a rank‐constrained time‐resolved reconstruction from the EVI data to capture spatially varying phases, (c) a model‐based phase correction for DW‐MRSI data, and (d) a multi‐ b ‐value subspace‐based method for water/lipids removal and spatiospectral reconstruction using learned metabolite subspaces, and e) a hybrid subspace and parametric model‐based parameter estimation strategy. Phantom and in vivo experiments were performed to validate the proposed method and demonstrate its ability to map metabolite‐specific diffusion parameters in 3D. Results The proposed method generated reproducible metabolite diffusion coefficient estimates, consistent with those from a standard single‐voxel DW spectroscopy (SV‐DWS) method. High‐SNR multi‐molecular mean diffusivity (MD) maps can be obtained at a 6.9  × $$ \times $$ 6.9× $$ \times $$ 7.0 mm  3 $$ {}^3 $$ nominal resolution with large 3D brain coverage. High‐resolution (4.4× $$ \times $$ 4.4× $$ \times $$ 5.6 mm  3$$ {}^3 $$ ) metabolite and diffusion coefficient maps can be obtained within 20 mins for the first time. Tissue‐dependent metabolite MDs were observed, i.e., larger MDs for NAA, creatine, and choline in white matter than gray matter, with region‐specific differences. Conclusion We demonstrated an unprecedented capability of simultaneous, high‐resolution metabolite and diffusion parameter mapping. This imaging capability has strong potential to offer richer molecular and tissue‐compartment‐specific microstructural information for various clinical and neuroscience applications.